HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
DUPIXENT safely and effectively. See full prescribing information for
DUPIXENT.

Dosage in Pediatric Patients 6 to 11 Years of Age (2.4):
Body Weight
Initial Dose and Subsequent Dosage
15 to less than 30 kg
300 mg every four weeks (Q4W)≥30 kg
200 mg every other week (Q2W)
For pediatric patients 6 to 11 years old with asthma and co-morbid moderateto-severe atopic dermatitis, follow the recommended dosage as per Table 2
which includes an initial loading dose. (2.3)

DUPIXENT® (dupilumab) injection, for subcutaneous use
Initial U.S. Approval: 2017___________________________________
RECENT MAJOR CHANGES
Indications and Usage, Chronic Rhinosinusitis with
Nasal Polyps (1.3)
09/2024
Indications and Usage, Eosinophilic Esophagitis (1.4)
01/2024
Dosage and Administration, 100 mg Q2W inpediatric patients 6 to 11 years of age with asthma (2.4)
Removed 04/2024
Dosage and Administration, Chronic Rhinosinusitis
with Nasal Polyps (2.5)
09/2024
Dosage and Administration, Eosinophilic Esophagitis(2.6)
01/2024
Warnings and Precautions, Conjunctivitis and Keratitis(5.2)
01/2024___________________________________
INDICATIONS AND USAGE
DUPIXENT is an interleukin-4 receptor alpha antagonist indicated:
Atopic Dermatitis
for the treatment of adult and pediatric patients aged 6 months and older
with moderate-to-severe AD whose disease is not adequately controlledwith topical prescription therapies or when those therapies are notadvisable. DUPIXENT can be used with or without topical corticosteroids.
(1.1)
Asthmaas an add-on maintenance treatment of adult and pediatric patients aged 6
years and older with moderate-to-severe asthma characterized by aneosinophilic phenotype or with oral corticosteroid dependent asthma. (1.2)
Limitations of Use: Not for the relief of acute bronchospasm or statusasthmaticus. (1.2)
Chronic Rhinosinusitis with Nasal Polyps
as an add-on maintenance treatment in adult and pediatric patients aged 12
years and older with inadequately controlled chronic rhinosinusitis withnasal polyps (CRSwNP). (1.3)
Eosinophilic Esophagitis
for the treatment of adult and pediatric patients aged 1 year and older,weighing at least 15 kg, with eosinophilic esophagitis (EoE). (1.4)
Prurigo Nodularis
for the treatment of adult patients with prurigo nodularis (PN). (1.5)_______________DOSAGE AND ADMINISTRATION______________

Atopic Dermatitis
Dosage in Adults (2.3):
Recommended dosage is an initial dose of 600 mg (two 300 mg injections),
followed by 300 mg given every other week (Q2W).
Dosage in Pediatric Patients 6 Months to 5 Years of Age (2.3):
Body Weight
Initial and Subsequent Dosage
5 to less than 15 kg
200 mg (one 200 mg injection) every 4 weeks (Q4W)
15 to less than 30 kg 300 mg (one 300 mg injection) every 4 weeks (Q4W)
Dosage in Pediatric Patients 6 Years to 17 Years of Age (2.3):
Body Weight
Initial Loading Dose
Subsequent
Dosagea
15 to less than 30 kg
600 mg (two 300 mg injections)
300 mg Q4W
30 to less than 60 kg
400 mg (two 200 mg injections)
200 mg Q2W
60 kg or more
600 mg (two 300 mg injections)
300 mg Q2Wa
Q2W – every other week; Q4W – every 4 weeks
AsthmaDosage in Adult and Pediatric Patients 12 Years and Older (2.4):
Initial Loading Dose
Subsequent Dosage
400 mg (two 200 mg injections)
200 mg every 2 weeks (Q2W)
Or
600 mg (two 300 mg injections)
300 mg every 2 weeks (Q2W)
Dosage for patients with oral corticosteroid-dependent asthma or withco-morbid moderate-to-severe atopic dermatitis or adults with comorbid chronic rhinosinusitis with nasal polyps
600 mg (two 300 mg injections)
300 mg every 2 weeks (Q2W)

Chronic Rhinosinusitis with Nasal Polyps (2.5):
Recommended dosage for adult and pediatric patients 12 years of age andolder is 300 mg given every other week (Q2W).
Eosinophilic Esophagitis (2.6):
Body Weight
15 to less than 30 kg
30 to less than 40 kg
40 kg or more

Recommended Dosage in Adult and PediatricPatients 1 Year and Older, Weighing At Least
15 kg
200 mg every other week (Q2W)
300 mg every other week (Q2W)
300 mg every week (QW)

Prurigo Nodularis (2.7):
Recommended dosage for adult patients is an initial dose of 600 mg (two
300 mg injections), followed by 300 mg given every other week (Q2W).
____________________________DOSAGE FORMS AND STRENGTHSSingle-Dose Pre-Filled Syringe with Needle Shield (3): Injection: 300 mg/2 mL
 Injection: 200 mg/1.14 mL
Single-Dose Pre-Filled Pen (3): Injection: 300 mg/2 mL
 Injection: 200 mg/1.14 mL_______________________________________
CONTRAINDICATIONS
Known hypersensitivity to dupilumab or any excipients in DUPIXENT. (4)_______________WARNINGS AND PRECAUTIONS_______________

 Hypersensitivity: Hypersensitivity reactions including anaphylaxis, serum













sickness, angioedema, urticaria, rash, erythema nodosum, and erythemamultiforme have occurred. Discontinue DUPIXENT in the event of a
hypersensitivity reaction. (5.1)
Conjunctivitis and Keratitis: Advise patients to report new onset or
worsening eye symptoms to their healthcare provider. Consider
ophthalmological examination, as appropriate. (5.2)
Eosinophilic Conditions: Be alert to vasculitic rash, worsening pulmonary
symptoms, and/or neuropathy, especially upon reduction of oralcorticosteroids. (5.3)
Reduction of Corticosteroid Dosage: Do not discontinue systemic, topical,
or inhaled corticosteroids abruptly upon initiation of DUPIXENT. Decreasesteroids gradually, if appropriate. (5.5)
Arthralgia: Advise patients to report new onset or worsening joint
symptoms to their healthcare provider. If symptoms persist or worsen,
consider rheumatological evaluation and/or discontinuation of DUPIXENT.
(5.7)
Parasitic (Helminth) Infections: Treat pre-existing helminth infections
before initiating DUPIXENT. If patients become infected while receiving
DUPIXENT and do not respond to anti-helminth treatment, discontinue
DUPIXENT until the infection resolves. (5.8)
Vaccinations: Avoid use of live vaccines. (5.9)________________________________________
ADVERSE REACTIONS
Most common adverse reactions are:
 Atopic Dermatitis (incidence ≥1%): injection site reactions, conjunctivitis,
blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus
infection, dry eye, and eosinophilia. (6.1)
 Asthma (incidence ≥1%): injection site reactions, oropharyngeal pain, andeosinophilia. (6.1)
 Chronic Rhinosinusitis with Nasal Polyps (incidence ≥1%): injection site
reactions, eosinophilia, insomnia, toothache, gastritis, arthralgia, andconjunctivitis. (6.1)
 Eosinophilic Esophagitis (incidence ≥2%): injection site reactions, upper
respiratory tract infections, arthralgia, and herpes viral infections. (6.1)
 Prurigo Nodularis (incidence ≥2%): nasopharyngitis, conjunctivitis, herpes
infection, dizziness, myalgia, and diarrhea. (6.1)

Page 1 of 57

To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at
1-844-387-4936 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

FULL PRESCRIBING INFORMATION: CONTENTS*
1
INDICATIONS AND USAGE
1.1 Atopic Dermatitis
1.2 Asthma
1.3 Chronic Rhinosinusitis with Nasal Polyps
1.4 Eosinophilic Esophagitis
1.5 Prurigo Nodularis
DOSAGE AND ADMINISTRATION
2
2.1 Important Administration Instructions
2.2 Vaccination Prior to Treatment
2.3 Recommended Dosage for Atopic Dermatitis
2.4 Recommended Dosage for Asthma
2.5 Recommended Dosage for Chronic Rhinosinusitis with Nasal
Polyps
2.6 Recommended Dosage for Eosinophilic Esophagitis
2.7 Recommended Dosage for Prurigo Nodularis
2.8 Missed Doses
2.9 Preparation for Use
3
DOSAGE FORMS AND STRENGTHS
4CONTRAINDICATIONS5WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity
5.2 Conjunctivitis and Keratitis
5.3 Eosinophilic Conditions
5.4 Acute Asthma Symptoms or Deteriorating Disease
5.5 Risk Associated with Abrupt Reduction of Corticosteroid
Dosage
5.6 Patients with Co-morbid Asthma
5.7 Arthralgia
5.8 Parasitic (Helminth) Infections

See 17 for PATIENT COUNSELING INFORMATION and FDAapproved patient labeling.
Revised: 09/2024

6
8

10
11
12

13
14

16
17

5.9 Vaccinations
ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
OVERDOSAGEDESCRIPTION
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
12.6 Immunogenicity
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
CLINICAL STUDIES
14.1 Atopic Dermatitis
14.2 Asthma
14.3 Chronic Rhinosinusitis with Nasal Polyps
14.4 Eosinophilic Esophagitis
14.5 Prurigo Nodularis
HOW SUPPLIED/STORAGE AND HANDLINGPATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information
are not listed.

Page 2 of 57

FULL PRESCRIBING INFORMATION
1

INDICATIONS AND USAGE

1.1

Atopic Dermatitis

DUPIXENT is indicated for the treatment of adult and pediatric patients aged 6 months and older
with moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with
topical prescription therapies or when those therapies are not advisable. DUPIXENT can be usedwith or without topical corticosteroids.

1.2

Asthma

DUPIXENT is indicated as an add-on maintenance treatment of adult and pediatric patients aged
6 years and older with moderate-to-severe asthma characterized by an eosinophilic phenotype orwith oral corticosteroid dependent asthma [see Clinical Studies (14)].
Limitations of Use
DUPIXENT is not indicated for the relief of acute bronchospasm or status asthmaticus.

1.3

Chronic Rhinosinusitis with Nasal Polyps

DUPIXENT is indicated as an add-on maintenance treatment in adult and pediatric patients aged
12 years and older with inadequately controlled chronic rhinosinusitis with nasal polyps(CRSwNP).

1.4

Eosinophilic Esophagitis

DUPIXENT is indicated for the treatment of adult and pediatric patients aged 1 year and older,weighing at least 15 kg, with eosinophilic esophagitis (EoE).

1.5

Prurigo Nodularis

DUPIXENT is indicated for the treatment of adult patients with prurigo nodularis (PN).

2DOSAGE AND ADMINISTRATION

2.1

Important Administration Instructions

DUPIXENT is administered by subcutaneous injection.
DUPIXENT is intended for use under the guidance of a healthcare provider. Provide proper
training to patients and/or caregivers on the preparation and administration of DUPIXENT prior
to use according to the “Instructions for Use”.
Use of Pre-filled Pen or Pre-filled Syringe
The DUPIXENT pre-filled pen is for use in adult and pediatric patients aged 2 years and older.
The DUPIXENT pre-filled syringe is for use in adult and pediatric patients aged 6 months andolder.
Page 3 of 57

A caregiver or patient 12 years of age and older may inject DUPIXENT using the pre-filled
syringe or pre-filled pen. In pediatric patients 12 to 17 years of age, administer DUPIXENT
under the supervision of an adult. In pediatric patients 6 months to less than 12 years of age,
administer DUPIXENT by a caregiver.
Administration Instructions
For AD, asthma, and PN patients taking an initial 600 mg dose, administer each of the two
DUPIXENT 300 mg injections at different injection sites.
For AD and asthma patients taking an initial 400 mg dose, administer each of the two
DUPIXENT 200 mg injections at different injection sites.
Administer subcutaneous injection into the thigh or abdomen, except for the 2 inches (5 cm)
around the navel. The upper arm can also be used if a caregiver administers the injection.
Rotate the injection site with each injection. DO NOT inject DUPIXENT into skin that is tender,
damaged, bruised, or scarred.
The DUPIXENT “Instructions for Use” contains more detailed instructions on the preparation
and administration of DUPIXENT [see Instructions for Use].

2.2

Vaccination Prior to Treatment

Consider completing all age-appropriate vaccinations as recommended by current immunization
guidelines prior to initiating treatment with DUPIXENT [see Warnings and Precautions (5.9)].

2.3

Recommended Dosage for Atopic Dermatitis

Dosage in Adults
The recommended dosage of DUPIXENT for adult patients is an initial dose of 600 mg (two
300 mg injections), followed by 300 mg given every other week (Q2W).
Dosage in Pediatric Patients 6 Months to 5 Years of Age
The recommended dosage of DUPIXENT for pediatric patients 6 months to 5 years of age is
specified in Table 1.
Table 1:

Dosage of DUPIXENT in Pediatric Patients 6 Months to 5 Years of Age with
Atopic Dermatitis

Body Weight
Initiala and Subsequent Dosage
5 to less than 15 kg
200 mg (one 200 mg injection) every 4 weeks (Q4W)
15 to less than 30 kg
300 mg (one 300 mg injection) every 4 weeks (Q4W)a
For pediatric patients 6 months to 5 years of age with AD, no initial loading dose is recommended.

Page 4 of 57

Dosage in Pediatric Patients 6 Years to 17 Years of Age
The recommended dosage of DUPIXENT for pediatric patients 6 years to 17 years of age is
specified in Table 2.
Table 2:

Dosage of DUPIXENT in Pediatric Patients 6 Years to 17 Years of Age with
Atopic Dermatitis

Body Weight
15 to less than 30 kg
30 to less than 60 kg
60 kg or more

Initial Loading Dose
600 mg (two 300 mg injections)
400 mg (two 200 mg injections)
600 mg (two 300 mg injections)

Subsequent Dosage
300 mg every 4 weeks (Q4W)
200 mg every other week (Q2W)
300 mg every other week (Q2W)

Concomitant Topical Therapies
DUPIXENT can be used with or without topical corticosteroids. Topical calcineurin inhibitors
may be used, but should be reserved for problem areas only, such as the face, neck, intertriginousand genital areas.

2.4

Recommended Dosage for Asthma

Dosage in Adult and Pediatric Patients 12 Years and Older
The recommended dosage of DUPIXENT for adult and pediatric patients 12 years of age andolder is specified in Table 3.
Table 3:

Dosage of DUPIXENT in Adult and Pediatric Patients 12 Years and Olderwith Asthma
Initial Loading Dose
400 mg (two 200 mg injections)

Subsequent Dosage
200 mg every 2 weeks (Q2W)
Or

600 mg (two 300 mg injections)
300 mg every 2 weeks (Q2W)
Dosage for patients with oral corticosteroid-dependent asthma or with co-morbid moderate-to-severe
atopic dermatitis or adults with co-morbid chronic rhinosinusitis with nasal polyps
600 mg (two 300 mg injections)
300 mg every 2 weeks (Q2W)

Dosage in Pediatric Patients 6 to 11 Years of Age
The recommended dosage of DUPIXENT for pediatric patients 6 to 11 years of age is specified
in Table 4.
Table 4:

Dosage of DUPIXENT in Pediatric Patients 6 to 11 Years of Age with
AsthmaBody Weight
Initiala and Subsequent Dosage
15 to less than 30 kg
300 mg every four weeks (Q4W)≥30 kg
200 mg every other week (Q2W)a
For pediatric patients 6 to 11 years of age with asthma, no initial loading dose is recommended.

Page 5 of 57

For pediatric patients 6 to 11 years of age with asthma and co-morbid moderate-to-severe AD,
follow the recommended dosage as per Table 2 which includes an initial loading dose [seeDosage and Administration (2.3)].

2.5

Recommended Dosage for Chronic Rhinosinusitis with Nasal Polyps

The recommended dosage of DUPIXENT for adult and pediatric patients 12 years of age andolder is 300 mg given every other week (Q2W).

2.6

Recommended Dosage for Eosinophilic Esophagitis

The recommended dosage of DUPIXENT for adult and pediatric patients 1 year of age and older,weighing at least 15 kg, is specified in Table 5.
Table 5:

Dosage of DUPIXENT in Adult and Pediatric Patients 1 Year of Age andOlder with Eosinophilic Esophagitis

Body Weight
15 to less than 30 kg
30 to less than 40 kg
40 kg or more

2.7

Recommended Dosage
200 mg every other week (Q2W)
300 mg every other week (Q2W)
300 mg every week (QW)

Recommended Dosage for Prurigo Nodularis

The recommended dosage of DUPIXENT for adult patients is an initial dose of 600 mg (two
300 mg injections) followed by 300 mg given every other week (Q2W).

2.8

Missed Doses

If a weekly dose is missed, administer the dose as soon as possible, and start a new weekly
schedule from the date of the last administered dose.
If an every other week dose is missed, administer the injection within 7 days from the missed
dose and then resume the patient’s original schedule. If the missed dose is not administered
within 7 days, wait until the next dose on the original schedule.
If an every 4 week dose is missed, administer the injection within 7 days from the missed dose
and then resume the patient’s original schedule. If the missed dose is not administered within 7days, administer the dose, starting a new schedule based on this date.

2.9

Preparation for Use

Before injection, remove DUPIXENT from the refrigerator and allow DUPIXENT to reach room
temperature (45 minutes for the 300 mg/2 mL pre-filled syringe or pre-filled pen, and 30 minutes
for the 200 mg/1.14 mL pre-filled syringe or pre-filled pen) without removing the needle cap.
After removal from the refrigerator, DUPIXENT must be used within 14 days or discarded.
Inspect DUPIXENT visually for particulate matter and discoloration prior to administration.
DUPIXENT is a clear to slightly opalescent, colorless to pale yellow solution. Do not use if theliquid contains visible particulate matter, is discolored or cloudy (other than clear to slightly
opalescent, colorless to pale yellow). DUPIXENT does not contain preservatives; therefore,
discard any unused product remaining in the pre-filled syringe or pre-filled pen.
Page 6 of 57

3

DOSAGE FORMS AND STRENGTHSDUPIXENT is a clear to slightly opalescent, colorless to pale yellow solution in a:Single-dose pre-filled syringe with needle shield as:

Injection: 300 mg/2 mL

Injection: 200 mg/1.14 mL

Single-dose pre-filled pen as:

4Injection: 300 mg/2 mL

Injection: 200 mg/1.14 mL

CONTRAINDICATIONSDUPIXENT is contraindicated in patients who have known hypersensitivity to dupilumab or any
excipients of DUPIXENT [see Warnings and Precautions (5.1)].

5

WARNINGS AND PRECAUTIONS

5.1

Hypersensitivity

Hypersensitivity reactions, including anaphylaxis, serum sickness or serum sickness-likereactions, angioedema, generalized urticaria, rash, erythema nodosum, and erythema multiforme
have been reported. If a clinically significant hypersensitivity reaction occurs, instituteappropriate therapy and discontinue DUPIXENT [see Adverse Reactions (6.1, 6.2) and ClinicalPharmacology (12.6)].

5.2

Conjunctivitis and Keratitis

Conjunctivitis and keratitis adverse reactions have been reported in clinical trials.
Conjunctivitis and keratitis occurred more frequently in AD subjects who received DUPIXENT
compared to those who received placebo. Conjunctivitis was the most frequently reported eye
disorder. Most subjects with conjunctivitis or keratitis recovered or were recovering during thetreatment period [see Adverse Reactions (6.1)].
Among subjects with asthma, the frequencies of conjunctivitis and keratitis were similar between
DUPIXENT and placebo [see Adverse Reactions (6.1)].
In adult subjects with CRSwNP, the frequency of conjunctivitis was 2% in the DUPIXENT
group compared to 1% in the placebo group in the 24-week safety pool; these subjects recovered.
There were no cases of keratitis reported in the CRSwNP development program [see Adverse
Reactions (6.1)].
Among subjects with EoE, there were no reports of conjunctivitis and keratitis in the
DUPIXENT group in placebo-controlled trials [see Adverse Reactions (6.1)].
In subjects with PN, the frequency of conjunctivitis was 4% in the DUPIXENT group compared
to 1% in the placebo group; these subjects recovered or were recovering during the treatment

Page 7 of 57

period. There were no cases of keratitis reported in the PN development program [see Adverse
Reactions (6.1)].
Conjunctivitis and keratitis adverse events have also been reported with DUPIXENT in
postmarketing settings, predominantly in AD patients. Some patients reported visual
disturbances (e.g., blurred vision) associated with conjunctivitis or keratitis.
Advise patients or their caregivers to report new onset or worsening eye symptoms to theirhealthcare provider. Consider ophthalmological examination for patients who develop
conjunctivitis that does not resolve following standard treatment or signs and symptoms
suggestive of keratitis, as appropriate [see Adverse Reactions (6.1)].

5.3

Eosinophilic Conditions

Patients being treated for asthma may present with serious systemic eosinophilia sometimes
presenting with clinical features of eosinophilic pneumonia or vasculitis consistent witheosinophilic granulomatosis with polyangiitis, conditions which are often treated with systemic
corticosteroid therapy. These events may be associated with the reduction of oral corticosteroid
therapy. Healthcare providers should be alert to vasculitic rash, worsening pulmonary symptoms,
cardiac complications, and/or neuropathy presenting in their patients with eosinophilia. Cases of
eosinophilic pneumonia were reported in adult subjects who participated in the asthma
development program and cases of vasculitis consistent with eosinophilic granulomatosis withpolyangiitis have been reported with DUPIXENT in adult subjects who participated in theasthma development program as well as in adult subjects with co-morbid asthma in the CRSwNP
development program. A causal association between DUPIXENT and these conditions has notbeen established.

5.4

Acute Asthma Symptoms or Deteriorating Disease

DUPIXENT should not be used to treat acute asthma symptoms or acute exacerbations. Do not
use DUPIXENT to treat acute bronchospasm or status asthmaticus. Patients should seek medical
advice if their asthma remains uncontrolled or worsens after initiation of treatment with
DUPIXENT.

5.5

Risk Associated with Abrupt Reduction of Corticosteroid Dosage

Do not discontinue systemic, topical, or inhaled corticosteroids abruptly upon initiation oftherapy with DUPIXENT. Reductions in corticosteroid dose, if appropriate, should be gradualand performed under the direct supervision of a healthcare provider. Reduction in corticosteroid
dose may be associated with systemic withdrawal symptoms and/or unmask conditions
previously suppressed by systemic corticosteroid therapy.

5.6

Patients with Co-morbid Asthma

Advise patients with co-morbid asthma not to adjust or stop their asthma treatments without
consultation with their physicians.

Page 8 of 57

5.7

Arthralgia

Arthralgia has been reported with the use of DUPIXENT with some patients reporting gait
disturbances or decreased mobility associated with joint symptoms; some cases resulted in
hospitalization [see Adverse Reactions (6.1)]. In postmarketing reports, onset of arthralgia wasvariable, ranging from days to months after the first dose of DUPIXENT. Some patients’
symptoms resolved while continuing treatment with DUPIXENT and other patients recovered orwere recovering following discontinuation of DUPIXENT.
Advise patients to report new onset or worsening joint symptoms to their healthcare provider. If
symptoms persist or worsen, consider rheumatological evaluation and/or discontinuation of
DUPIXENT.

5.8

Parasitic (Helminth) Infections

Patients with known helminth infections were excluded from participation in clinical studies. It is
unknown if DUPIXENT will influence the immune response against helminth infections.
Treat patients with pre-existing helminth infections before initiating therapy with DUPIXENT. If
patients become infected while receiving treatment with DUPIXENT and do not respond to antihelminth treatment, discontinue treatment with DUPIXENT until the infection resolves. Adverse
reactions of helminth infections (5 cases of enterobiasis and 1 case of ascariasis) were reported inpediatric subjects 6 to 11 years old who participated in the pediatric asthma development
program [see Adverse Reactions (6.1)].

5.9

Vaccinations

Consider completing all age-appropriate vaccinations as recommended by current immunization
guidelines prior to initiating treatment with DUPIXENT. Avoid use of live vaccines during
treatment with DUPIXENT. It is unknown if administration of live vaccines during DUPIXENT
treatment will impact the safety or effectiveness of these vaccines. Limited data are available
regarding coadministration of DUPIXENT with non-live vaccines [see Clinical Pharmacology(12.2)].

6

ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

6.1

Hypersensitivity [see Warnings and Precautions (5.1)]

Conjunctivitis and Keratitis [see Warnings and Precautions (5.2)]



Arthralgia [see Warnings and Precautions (5.7)]

Parasitic (Helminth) Infections [see Warnings and Precautions (5.8)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trialsof another drug and may not reflect the rates observed in practice.

Page 9 of 57

Adults with Atopic Dermatitis
Three randomized, double-blind, placebo-controlled, multicenter trials (SOLO 1, SOLO 2, and
CHRONOS) and one dose-ranging trial (AD-1021) evaluated the safety of DUPIXENT insubjects with moderate-to-severe AD. The safety population had a mean age of 38 years; 41% ofsubjects were female, 67% were White, 24% were Asian, and 6% were Black; in terms of comorbid conditions, 48% of the subjects had asthma, 49% had allergic rhinitis, 37% had foodallergy, and 27% had allergic conjunctivitis. In these 4 trials, 1472 subjects were treated with
subcutaneous injections of DUPIXENT, with or without concomitant topical corticosteroids(TCS).
A total of 739 subjects were treated with DUPIXENT for at least 1 year in the development
program for moderate-to-severe AD.
SOLO 1, SOLO 2, and AD-1021 compared the safety of DUPIXENT monotherapy to placebothrough Week 16. CHRONOS compared the safety of DUPIXENT + TCS to placebo + TCS
through Week 52.
AD-1225 is a multicenter, open-label extension (OLE) trial which assessed the long-term safetyof repeat doses of DUPIXENT through 260 weeks of treatment in adults with moderate-to-severe
AD who had previously participated in controlled trials of DUPIXENT or had been screened for
SOLO 1 or SOLO 2. The safety data in AD-1225 reflect exposure to DUPIXENT 200 mg QW,
300 mg QW and 300 mg Q2W in 2677 subjects, including 2254 exposed for at least 52 weeks,1224 exposed for at least 100 weeks, 561 exposed for at least 148 weeks and 179 exposed for atleast 260 weeks.
Weeks 0 to 16 (SOLO 1, SOLO 2, CHRONOS, and AD-1021)
In DUPIXENT monotherapy trials (SOLO 1, SOLO 2, and AD-1021) through Week 16, theproportion of subjects who discontinued treatment because of adverse events was 1.9% in boththe DUPIXENT 300 mg Q2W and placebo groups. Table 6 summarizes the adverse reactions
that occurred at a rate of at least 1% in the DUPIXENT 300 mg Q2W monotherapy groups, andin the DUPIXENT + TCS group, all at a higher rate than in their respective comparator groups
during the first 16 weeks of treatment.
Table 6:Adverse Reactions Occurring in ≥1% of the DUPIXENT MonotherapyGroup or the DUPIXENT + TCS Group in the Atopic Dermatitis Trials
through Week 16

Adverse Reaction

Injection site reaction
Conjunctivitisd
Blepharitis
Oral herpes
Keratitise
Eye pruritus

DUPIXENT Monotherapya
DUPIXENT
Placebo
300 mg Q2Wc
N=529
n (%)
51 (10)51 (10)2 (<1)
20 (4)
1 (<1)
3 (1)

N=517
n (%)
28 (5)
12 (2)
1 (<1)
8 (2)0
1 (<1)

Page 10 of 57

DUPIXENT + TCSb
DUPIXENT
Placebo +TCS
300 mg Q2Wc + TCS
N=110
n (%)
11 (10)10 (9)
5 (5)
3 (3)
4 (4)
2 (2)

N=315
n (%)
18 (6)
15 (5)
2 (1)
5 (2)
0
2 (1)

Other herpes simplex
10 (2)6 (1)1 (1)
1 (<1)
virus infectionf
Dry eye1 (<1)0
2 (2)1 (<1)aPooled analysis of SOLO 1, SOLO 2, and AD-1021.
b
Analysis of CHRONOS where subjects were on background TCS therapy.
c
DUPIXENT 600 mg at Week 0, followed by 300 mg every two weeks.
dConjunctivitis cluster includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis,
giant papillary conjunctivitis, eye irritation, and eye inflammation.
e
Keratitis cluster includes keratitis, ulcerative keratitis, allergic keratitis, atopic keratoconjunctivitis, andophthalmic herpes simplex.
fOther herpes simplex virus infection cluster includes herpes simplex, genital herpes, herpes simplex otitis externa,and herpes virus infection, but excludes eczema herpeticum.

Safety through Week 52 (CHRONOS)
In the DUPIXENT with concomitant TCS trial (CHRONOS) through Week 52, the proportion ofsubjects who discontinued treatment because of adverse events was 1.8% in DUPIXENT 300 mg
Q2W + TCS group and 7.6% in the placebo + TCS group. Two subjects discontinued
DUPIXENT because of adverse reactions: atopic dermatitis (1 subject) and exfoliative dermatitis(1 subject).
The safety profile of DUPIXENT + TCS through Week 52 was generally consistent with thesafety profile observed at Week 16.
Safety through 260 Weeks (AD-1225)
The long-term safety profile observed in this trial through 260 weeks was generally consistent
with the safety profile of DUPIXENT observed in controlled studies.
Pediatric Subjects 12 to 17 Years of Age with Atopic Dermatitis
The safety of DUPIXENT was assessed in a trial of 250 pediatric subjects 12 to 17 years of age
with moderate-to-severe AD (AD-1526). The safety profile of DUPIXENT in these subjects
through Week 16 was similar to the safety profile seen in adults with AD.
The long-term safety of DUPIXENT was assessed in an open-label extension study in pediatricsubjects 12 to 17 years of age with moderate-to-severe AD (AD-1434). The safety profile of
DUPIXENT in subjects followed through Week 52 was similar to the safety profile observed at
Week 16 in AD-1526. The long-term safety profile of DUPIXENT observed in pediatric subjects
12 to 17 years of age was consistent with that seen in adults with AD.
Pediatric Subjects 6 to 11 Years of Age with Atopic Dermatitis
The safety of DUPIXENT with concomitant TCS was assessed in a trial of 367 pediatric subjects
6 to 11 years of age with severe AD (AD-1652). The safety profile of DUPIXENT + TCS in
these subjects through Week 16 was similar to the safety profile from trials in adult and pediatricsubjects 12 to 17 years of age with AD.
The long-term safety of DUPIXENT ± TCS was assessed in an open-label extension study of
368 pediatric subjects 6 to 11 years of age with AD (AD-1434). Among subjects who entered
this study, 110 (30%) had moderate and 72 (20%) had severe AD at the time of enrollment in
AD-1434. The safety profile of DUPIXENT ± TCS in subjects followed through Week 52 wassimilar to the safety profile observed through Week 16 in AD-1652. The long-term safety profile
of DUPIXENT ± TCS observed in pediatric subjects 6 to 11 years of age was consistent with
Page 11 of 57

that seen in adult and pediatric subjects 12 to 17 years of age with AD [see Use in Specific
Populations (8.4)].
Pediatric Subjects 6 Months to 5 Years of Age with Atopic Dermatitis
The safety of DUPIXENT with concomitant TCS was assessed in a trial of 161 pediatric subjects
6 months to 5 years of age with moderate-to-severe AD (AD-1539). The safety profile of
DUPIXENT + TCS in these subjects through Week 16 was similar to the safety profile fromtrials in adults and pediatric subjects 6 to 17 years of age with AD.
The long-term safety of DUPIXENT ± TCS was assessed in an open-label extension study of
180 pediatric subjects 6 months to 5 years of age with AD (AD-1434). The majority of subjects
were treated with DUPIXENT 300 mg every 4 weeks. The safety profile of DUPIXENT ± TCS
in subjects followed through Week 52 was similar to the safety profile observed through Week
16 in AD-1539. The long-term safety profile of DUPIXENT ± TCS observed in pediatricsubjects 6 months to 5 years of age was consistent with that seen in adults and pediatric subjects
6 to 17 years old with AD. In addition, hand-foot-and-mouth disease was reported in 9 (5%)
pediatric subjects and skin papilloma was reported in 4 (2%) pediatric subjects treated with
DUPIXENT ± TCS. These cases did not lead to study drug discontinuation [see Use in Specific
Populations (8.4)].
Atopic Dermatitis with Hand and/or Foot Involvement
The safety of DUPIXENT was assessed in a 16-week, multicenter, randomized, double-blind,parallel-group, placebo-controlled trial (Liberty-AD-HAFT) in 133 adult and pediatric subjects
12 to 17 years of age with atopic dermatitis with moderate-to-severe hand and/or footinvolvement [see Clinical Studies (14)]. In this trial 67 subjects received DUPIXENT, and 66
subjects received placebo. DUPIXENT-treated subjects received the recommended dosage basedon their age and body weight [see Dosage and Administration (2.3)]. The safety profile of
DUPIXENT in these subjects through Week 16 was consistent with the safety profile fromstudies in adult and pediatric subjects 6 months of age and older with moderate-to-severe AD.
AsthmaAdults and Pediatric Subjects 12 Years of Age and Older with Asthma
A total of 2888 adult and pediatric subjects 12 to 17 years of age with moderate-to-severe asthma(AS) were evaluated in 3 randomized, placebo-controlled, multicenter trials of 24 to 52 weeks
duration (DRI12544, QUEST, and VENTURE). Of these, 2678 had a history of 1 or more severe
exacerbations in the year prior to enrollment despite regular use of medium to high-dose inhaledcorticosteroids plus an additional controller(s) (DRI12544 and QUEST). A total of 210 subjects
with oral corticosteroid-dependent asthma receiving high-dose inhaled corticosteroids plus up to
two additional controllers were enrolled (VENTURE). The safety population (DRI12544 and
QUEST) was 12-87 years of age, of which 63% were female, and 82% were White. DUPIXENT
200 mg or 300 mg was administered subcutaneously Q2W, following an initial dose of 400 mg
or 600 mg, respectively.
In DRI12544 and QUEST, the proportion of subjects who discontinued treatment due to adverse
events was 4% of the placebo group, 3% of the DUPIXENT 200 mg Q2W group, and 6% of the
DUPIXENT 300 mg Q2W group.

Page 12 of 57

Table 7 summarizes the adverse reactions that occurred at a rate of at least 1% in subjects treatedwith DUPIXENT and at a higher rate than in their respective comparator groups in DRI12544
and QUEST.
Table 7:Adverse Reactions Occurring in ≥1% of Adult and Pediatric Subjects 12
Years of Age and Older with Asthma in the DUPIXENT Groups in
DRI12544 and QUEST and Greater than Placebo (6 Month Safety Pool)

Adverse Reaction
DUPIXENT
200 mg Q2W

DRI12544 and QUESTDUPIXENT
300 mg Q2W

Placebo

N=779
N=788
N=792
n (%)
n (%)
n (%)
Injection site reactionsa
111 (14%)144 (18%)50 (6%)
Oropharyngeal pain
13 (2%)
19 (2%)
7 (1%)
Eosinophiliab
17 (2%)
16 (2%)
2 (<1%)
aInjection site reactions cluster includes erythema, edema, pruritus, pain, and inflammation.
b
Eosinophilia = blood eosinophils ≥3,000 cells/mcL or deemed by the investigator to be an adverse event. None
met the criteria for serious eosinophilic conditions [see Warnings and Precautions (5.3)].

Injection site reactions were most common with the loading (initial) dose.
The safety profile of DUPIXENT through Week 52 was generally consistent with the safety
profile observed at Week 24.
Pediatric Subjects 6 to 11 Years of Age with Asthma
The safety of DUPIXENT was assessed in 405 pediatric subjects 6 to 11 years of age withmoderate-to-severe asthma (VOYAGE). The safety profile of DUPIXENT in these subjects
through Week 52 was similar to the safety profile from studies in adult and pediatric subjects 12
years of age and older with moderate-to-severe asthma with the addition of helminth infections.
Helminth infections were reported in 2.2% (6 subjects) in the DUPIXENT group and 0.7% (1subject) in the placebo group. The majority of cases were enterobiasis, reported in 1.8% (5subjects) in the DUPIXENT group and none in the placebo group. There was one case of
ascariasis in the DUPIXENT group. All helminth infection cases were mild to moderate andsubjects recovered with anti-helminth treatment without DUPIXENT treatment discontinuation.
Chronic Rhinosinusitis with Nasal Polyps
A total of 722 adult subjects with chronic rhinosinusitis with nasal polyps (CRSwNP) were
evaluated in 2 randomized, placebo-controlled, multicenter trials of 24 to 52 weeks duration(SINUS-24 and SINUS-52). The safety pool consisted of data from the first 24 weeks oftreatment from both studies.
In the safety pool, the proportion of adult subjects who discontinued treatment due to adverse
events was 5% of the placebo group and 2% of the DUPIXENT 300 mg Q2W group.
Table 8 summarizes the adverse reactions that occurred at a rate of at least 1% in adult subjects
treated with DUPIXENT and at a higher rate than in their respective comparator group in
SINUS-24 and SINUS-52.

Page 13 of 57

Table 8:

Adverse Reactions Occurring in ≥1% of Adult Subjects with CRSwNP in the
DUPIXENT Group in SINUS-24 and SINUS-52 and Greater than Placebo(24-Week Safety Pool)

Adverse Reaction

SINUS-24 and SINUS-52
DUPIXENT
300 mg Q2W

Placebo

N=440
N=282
n (%)
n (%)
Injection site reactionsa
28 (6%)
12 (4%)
Conjunctivitisb
7 (2%)
2 (1%)
Arthralgia
14 (3%)
5 (2%)
Gastritis
7 (2%)
2 (1%)
Insomnia
6 (1%)
0 (<1%)
Eosinophilia
5 (1%)
1 (<1%)
Toothache
5 (1%)
1 (<1%)
aInjection site reactions cluster includes injection site reaction, pain, bruising and swelling.
b
Conjunctivitis cluster includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis,
giant papillary conjunctivitis, eye irritation, and eye inflammation.

The safety profile of DUPIXENT through Week 52 was generally consistent with the safety
profile observed at Week 24.
Eosinophilic Esophagitis
Adults and Pediatric Subjects 12 Years of Age and Older with EoE
A total of 239 adult and pediatric subjects 12 years of age and older, weighing at least 40 kg,
with EoE were evaluated in a randomized, double-blind, parallel-group, multicenter, placebocontrolled trial, including two 24-week treatment periods (Study EoE-1 Parts A and B) andreceived either DUPIXENT 300 mg QW or placebo [see Clinical Studies (14.4)].
The proportion of subjects who discontinued treatment due to adverse events was 2% of theplacebo group and 2% of the DUPIXENT 300 mg QW group.
Table 9 summarizes the adverse reactions that occurred at a rate of at least 2% in subjects treatedwith DUPIXENT and at a higher rate than in their respective comparator group in Parts A and B.
Table 9:Adverse Reactions Occurring in ≥2% of Adult and Pediatric Subjects 12
Years of Age and Older with EoE Treated with DUPIXENT in a PlaceboControlled Trial (Study EoE-1 Parts A and B; 24-Week Safety Pool)

Study EoE-1 Parts A and B
DUPIXENT 300 mg QW
Placebo
N=122
N=117
n (%)
n (%)
Injection site reactionsa
46 (38%)39 (33%)Upper respiratory tract infectionsb
22 (18%)12 (10%)
Arthralgia
3 (2%)
1 (1%)
Herpes viral infectionsc
3 (2%)
1 (1%)
aInjection site reactions are composed of several terms including, but not limited to, injection site swelling, pain,
and bruising.
b
Upper respiratory tract infections are composed of several terms including, but not limited to, COVID-19,
sinusitis, and upper respiratory tract infection.
c
Herpes viral infections are composed of oral herpes and herpes simplex.
Adverse Reaction

Page 14 of 57

The safety profile of DUPIXENT in 72 pediatric subjects 12 to 17 years of age, weighing at least
40 kg, and adults in Parts A and B was similar.
Pediatric Subjects 1 to 11 Years of Age, Weighing at least 15 kg, with EoE
A total of 61 pediatric subjects 1 to 11 years of age, weighing at least 15 kg, with EoE were
evaluated in a randomized, blinded, parallel-group, multicenter trial, including an initial 16-week
placebo-controlled treatment period (Study EoE-2 Part A) and a 36-week extended active
treatment period (Study EoE-2 Part B). Subjects in Part A received a weight-based dosing
regimen of DUPIXENT or placebo [see Clinical Studies (14.4)]. All subjects in Part B
completed Part A and received active treatment with weight-based dosing regimens of
DUPIXENT in Part B (N=47).
The safety profile of DUPIXENT through Week 16 of Study EoE-2 Part A was generally similar
to the safety profile in adult and pediatric subjects 12 years of age and older with EoE. In Part B,a helminth infection was reported in one DUPIXENT-treated subject.
Prurigo Nodularis
A total of 309 adult subjects with prurigo nodularis (PN) were evaluated in two 24-weekrandomized, double-blind, placebo-controlled, multicenter trials (PRIME and PRIME2). The
safety pool included data from the 24-week treatment and 12-week follow-up periods from both
trials.
The proportion of subjects who discontinued treatment due to adverse events was 3% of theplacebo group and 0% of the DUPIXENT 300 mg Q2W group.
The safety population had a mean age of 49 years; 65% of subjects were female, 56% wereWhite, 34% were Asian, and 6% were Black or African American. Subjects with co-morbid
conditions included 43% of subjects with a history of atopy (defined as having a medical historyof AD, allergic rhinitis/rhinoconjunctivitis, asthma, or food allergy), 8% of subjects with ahistory of hypothyroidism and 9% of subjects with a history of diabetes mellitus type 2.
Table 10 summarizes the adverse reactions that occurred at a rate of at least 2% in subjects
treated with DUPIXENT and at a higher rate than in their respective comparator group in
PRIME and PRIME2.
Table 10:Adverse Reactions Occurring in ≥2% of the DUPIXENT Group in PRIME
and PRIME2 and Greater than Placebo
Adverse Reaction

Nasopharyngitisa
Conjunctivitisb
Herpes Infectionc
Dizzinessd
Myalgiae
DiarrheaaNasopharyngitis includes pharyngitis

PRIME and PRIME2
DUPIXENT
Placebo
300 mg Q2W
N=152
n (%)
8 (5%)
6 (4%)
5 (3%)
5 (3%)
5 (3%)
4 (3%)

Page 15 of 57

N=157
n (%)
3 (2%)
2 (1%)0%
2 (1%)
2 (1%)
1 (1%)

b

Conjunctivitis includes conjunctivitis and allergic conjunctivitis.
Herpes infection includes oral herpes, genital herpes simplex, herpes zoster and ophthalmic herpes zosterdDizziness includes dizziness postural, vertigo and vertigo positionale
Myalgia includes musculoskeletal pain and musculoskeletal chest paincSpecific Adverse Reactions
Conjunctivitis and Keratitis
In adult subjects with AD, conjunctivitis was reported in 10% (34 per 100 subject-years) in the
300 mg Q2W dose group and in 2% of the placebo group (8 per 100 subject-years) during the
16-week treatment period of the monotherapy trials (SOLO 1, SOLO 2, and AD-1021). During
the 52-week treatment period of concomitant therapy AD trial (CHRONOS), conjunctivitis wasreported in 16% of the DUPIXENT 300 mg Q2W + TCS group (20 per 100 subject-years) and in
9% of the placebo + TCS group (10 per 100 subject-years). During the long-term OLE trial withdata through 260 weeks (AD-1225), conjunctivitis was reported in 21% of the DUPIXENT
group (12 per 100 subject-years).
In DUPIXENT AD monotherapy trials (SOLO 1, SOLO 2, and AD-1021) through Week 16,
keratitis was reported in <1% of the DUPIXENT group (1 per 100 subject-years) and in 0% of
the placebo group (0 per 100 subject-years). In the 52-week DUPIXENT + topicalcorticosteroids (TCS) AD trial (CHRONOS), keratitis was reported in 4% of the DUPIXENT +TCS group (4 per 100 subject-years) and in 2% of the placebo + TCS group (2 per 100 subjectyears). Conjunctivitis and keratitis occurred more frequently in AD subjects who received
DUPIXENT. Conjunctivitis was the most frequently reported eye disorder. During the long-term
OLE trial with data through 260 weeks (AD-1225), keratitis was reported in 3% of the
DUPIXENT group (1 per 100 subject-years). Most subjects with conjunctivitis or keratitis
recovered or were recovering during the treatment period.
Among subjects with asthma, the frequency of conjunctivitis and keratitis was similar between
DUPIXENT and placebo.
In adult subjects with CRSwNP, the frequency of conjunctivitis was 2% in the DUPIXENT
group compared to 1% in the placebo group in the 24-week safety pool; these subjects recovered.
In the 52-week CRSwNP study (SINUS-52), the frequency of conjunctivitis was 3% in the
DUPIXENT adult subjects and 1% in the placebo subjects; all of these subjects recovered. There
were no cases of keratitis reported in the CRSwNP development program [see Warnings andPrecautions (5.2)].
Among subjects with EoE, there were no reports of conjunctivitis and keratitis in the
DUPIXENT group in placebo-controlled trials [see Warnings and Precautions (5.2)]. In the 36week active treatment extension period of Study EoE-2 Part B, conjunctivitis was reported in 4%
of DUPIXENT-treated pediatric subjects with EoE.
Among subjects with PN, the frequency of conjunctivitis was 4% in the DUPIXENT groupcompared to 1% in the placebo group; all of these subjects recovered or were recovering during
the treatment period. There were no cases of keratitis reported in the PN development program[see Warnings and Precautions (5.2)].
Eczema Herpeticum and Herpes Zoster

Page 16 of 57

The rate of eczema herpeticum was similar in the placebo and DUPIXENT groups in the AD
trials. The rates remained stable through 260 weeks in the long-term OLE trial (AD-1225).
Herpes zoster was reported in <1% of the DUPIXENT groups (1 per 100 subject-years) and in<1% of the placebo group (1 per 100 subject-years) in the 16-week AD monotherapy trials. In
the 52-week DUPIXENT + TCS AD trial, herpes zoster was reported in 1% of the DUPIXENT +TCS group (1 per 100 subject-years) and 2% of the placebo + TCS group (2 per 100 subjectyears). During the long-term OLE trial with data through 260 weeks (AD-1225), 2.0% of
DUPIXENT-treated subjects reported herpes zoster (0.94 per 100 subject-years of follow up).
Among asthma subjects the frequency of herpes zoster was similar between DUPIXENT andplacebo. Among subjects with CRSwNP or EoE there were no reported cases of herpes zoster or
eczema herpeticum.
Among subjects with PN, herpes zoster and ophthalmic herpes zoster were each reported in <1%of the DUPIXENT group (1 per 100 subject-years) and 0% of the placebo group.
Hypersensitivity Reactions
Hypersensitivity reactions were reported in <1% of DUPIXENT-treated subjects. These included
anaphylaxis, serum sickness or serum sickness-like reactions, generalized urticaria, rash,erythema nodosum, and erythema multiforme [see Contraindications (4), Warnings andPrecautions (5.1), and Clinical Pharmacology (12.6)].
Eosinophils
DUPIXENT-treated subjects with AD, asthma, and CRSwNP had a greater initial increase frombaseline in blood eosinophil count compared to subjects treated with placebo. In adult subjects
with AD (SOLO 1, SOLO 2, and AD-1021), the mean and median increases in blood eosinophils
from baseline to Week 4 were 100 and 0 cells/mcL, respectively. In pediatric subjects <6 years
old with AD, the mean and median increases from baseline to week 4 were 478 and 90
cells/mcL, respectively.
In adult and pediatric subjects 12 years of age and older with asthma (DRI12544 and QUEST),the mean and median increases in blood eosinophils from baseline to Week 4 were 130 and 10
cells/mcL, respectively. In subjects 6 to 11 years of age with asthma (VOYAGE), the mean andmedian increases in blood eosinophils from baseline to Week 12 were 124 and 0 cells/mcL,
respectively.
In adult subjects with CRSwNP (SINUS-24 and SINUS-52), the mean and median increases inblood eosinophils from baseline to Week 16 were 150 and 50 cells/mcL, respectively.
An increase from baseline in blood eosinophil count was not observed in adult and pediatricsubjects 12 years of age and older with EoE treated with DUPIXENT as compared to placebo(Study EoE-1). In pediatric subjects 1 to 11 years of age with EoE (Study EoE-2 Part A), blood
eosinophil counts were generally consistent with those observed in Study EoE-1.
In subjects with PN (PRIME and PRIME2), the mean and median decrease in blood eosinophils
from baseline to Week 4 were 9 and 10 cells/mcL, respectively.
Across the trials for AD, asthma, and CRSwNP indications, the incidence of treatment-emergent
eosinophilia (≥500 cells/mcL) was similar in DUPIXENT and placebo groups. In the trials forPage 17 of 57

the PN indication, the incidence of treatment-emergent eosinophilia (≥500 cells/mcL) was lower
in DUPIXENT than in the placebo group.
Treatment-emergent eosinophilia (≥5,000 cells/mcL) was reported in <3% of DUPIXENTtreated subjects and <0.5% in placebo-treated subjects (SOLO 1, SOLO 2, and AD-1021;
DRI12544, QUEST, and VOYAGE; SINUS-24 and SINUS-52; PRIME and PRIME2). Bloodeosinophil counts declined to near baseline or remained below baseline levels (PRIME and
PRIME2) during study treatment. In study AD-1539, treatment-emergent eosinophilia(≥5,000 cells/mcL) was reported in 8% of DUPIXENT-treated subjects and 0% in placebotreated subjects [see Warnings and Precautions (5.3)].
Cardiovascular
In the 1-year placebo-controlled trial in adult and pediatric subjects 12 years of age and older
with asthma (QUEST), cardiovascular thromboembolic events (cardiovascular deaths, non-fatal
myocardial infarctions, and non-fatal strokes) were reported in 1 (0.2%) of the DUPIXENT 200
mg Q2W group, 4 (0.6%) of the DUPIXENT 300 mg Q2W group, and 2 (0.3%) of the placebogroup.
In the 1-year placebo-controlled trial in subjects with AD (CHRONOS), cardiovascularthromboembolic events (cardiovascular deaths, non-fatal myocardial infarctions, and non-fatal
strokes) were reported in 1 (0.9%) of the DUPIXENT + TCS 300 mg Q2W group, 0 (0.0%) of
the DUPIXENT + TCS 300 mg QW group, and 1 (0.3%) of the placebo + TCS group.
In the 24-week placebo-controlled trial in adult subjects with CRSwNP (SINUS-24),
cardiovascular thromboembolic events (cardiovascular deaths, non-fatal myocardial infarctions,and non-fatal strokes) were reported in 1 (0.7%) of the DUPIXENT group and 0 (0.0%) of theplacebo group. In the 1-year placebo-controlled trial in adult subjects with CRSwNP (SINUS52), there were no cases of cardiovascular thromboembolic events (cardiovascular deaths, nonfatal myocardial infarctions, and non-fatal strokes) reported in any treatment arm.
In the 24-week placebo-controlled trial in subjects with EoE (Study EoE-1 Parts A and B), there
were no cases of cardiovascular thromboembolic events (cardiovascular deaths, non-fatal
myocardial infarctions, and non-fatal strokes) reported in any treatment arm.

6.2

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of DUPIXENT.
Because these reactions are reported voluntarily from a population of uncertain size, it is notalways possible to reliably estimate their frequency or establish a causal relationship to drug
exposure.
Immune system disorders: angioedema [see Warnings and Precautions (5.1)]
Skin and subcutaneous tissue disorders: Facial skin reactions, including erythema, rash, scaling,edema, papules, pruritus, burning, and pain

Page 18 of 57

8

USE IN SPECIFIC POPULATIONS

8.1

Pregnancy

Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to
DUPIXENT during pregnancy.
Healthcare providers and patients may call 1-877-311-8972 or go tohttps://mothertobaby.org/ongoing-study/dupixent/ to enroll in or to obtain information about theregistry.
Risk Summary
Available data from case reports and case series with DUPIXENT use in pregnant women havenot identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or
fetal outcomes. Human IgG antibodies are known to cross the placental barrier; therefore,
DUPIXENT may be transmitted from the mother to the developing fetus. There are adverse
effects on maternal and fetal outcomes associated with asthma in pregnancy (see Clinical
Considerations). In an enhanced pre- and post-natal developmental study, no adverse
developmental effects were observed in offspring born to pregnant monkeys after subcutaneousadministration of a homologous antibody against interleukin-4-receptor alpha (IL-4Rα) duringorganogenesis through parturition at doses up to 10-times the maximum recommended humandose (MRHD) (see Data).
The background risk of major birth defects and miscarriage for the indicated populations are
unknown. All pregnancies have a background risk of birth defect, loss or other adverse
outcomes. In the U.S. general population, the estimated background risk of major birth defects
and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Disease-Associated Maternal and/or Embryo-fetal Risk
In women with poorly or moderately controlled asthma, evidence demonstrates that there is anincreased risk of preeclampsia in the mother and prematurity, low birth weight, and small for
gestational age in the neonate. The level of asthma control should be closely monitored in
pregnant women and treatment adjusted as necessary to maintain optimal control.
Data
Animal Data
In an enhanced pre- and post-natal development toxicity study, pregnant cynomolgus monkeys
were administered weekly subcutaneous doses of homologous antibody against IL-4Rα up to 10
times the MRHD (on a mg/kg basis of 100 mg/kg/week) from the beginning of organogenesis toparturition. No treatment-related adverse effects on embryo-fetal toxicity or malformations, or onmorphological, functional, or immunological development were observed in the infants frombirth through 6 months of age.

Page 19 of 57

8.2

Lactation

Risk Summary
There are no data on the presence of dupilumab in human milk, the effects on the breastfed
infant, or the effects on milk production. Maternal IgG is known to be present in human milk.
The effects of local gastrointestinal exposure and limited systemic exposure to dupilumab on thebreastfed infant are unknown. The developmental and health benefits of breastfeeding should beconsidered along with the mother’s clinical need for DUPIXENT and any potential adverse
effects on the breastfed child from DUPIXENT or from the underlying maternal condition.

8.4

Pediatric Use

Atopic Dermatitis
The safety and effectiveness of DUPIXENT have been established in pediatric patients 6 monthsof age and older with moderate-to-severe AD, whose disease is not adequately controlled with
topical prescription therapies or when those therapies are not advisable [see Clinical Studies(14.1)].
Use of DUPIXENT in this age group is supported by data from the following clinical trials:


AD-1526 which included 251 pediatric subjects 12 to 17 years of age with moderate-tosevere AD. Of the 251 subjects, 82 were treated with DUPIXENT 200 mg Q2W (<60 kg)
or 300 mg Q2W (≥60 kg) and 85 were treated with matching placebo

AD-1652 which included 367 pediatric subjects 6 to 11 years of age with severe AD. Of
the 367 subjects, 120 were treated with DUPIXENT 300 mg Q4W + TCS (15 to <30 kg)
or 200 mg Q2W + TCS (≥30 kg) and 123 were treated with matching placebo + TCS



AD-1539 which included 162 pediatric subjects 6 months to 5 years of age withmoderate-to-severe AD. Of the 162 subjects, 83 were treated with DUPIXENT 200 mg
Q4W + TCS (5 to <15 kg) or 300 mg Q4W + TCS (15 to <30 kg) and 79 subjects wereassigned to be treated with matching placebo + TCS



AD-1434, an open-label extension study that enrolled 275 pediatric subjects 12 to 17
years of age treated with DUPIXENT ± TCS, 368 pediatric subjects 6 to 11 years of age
treated with DUPIXENT ± TCS, and 180 pediatric subjects 6 months to 5 years of age
treated with DUPIXENT ± TCSLiberty-AD-HAFT which included 27 pediatric subjects 12 to 17 years of age with atopic
dermatitis with moderate-to-severe hand and/or foot involvement treated with
DUPIXENT (N=14) or matching placebo (N=13)

The safety and effectiveness were generally consistent between pediatric and adult patients [seeAdverse Reactions (6.1) and Clinical Studies (14.1)]. In addition, hand-foot-and-mouth disease
was reported in 9 (5%) pediatric subjects and skin papilloma was reported in 4 (2%) pediatricsubjects 6 months to 5 years of age treated with DUPIXENT ± TCS in AD-1434. These cases did
not lead to study drug discontinuation [see Adverse Reactions (6.1)].
Safety and effectiveness in pediatric patients younger than 6 months of age with AD have notbeen established.
Page 20 of 57

Asthma
The safety and effectiveness of DUPIXENT for an add-on maintenance treatment in patientswith moderate-to-severe asthma characterized by an eosinophilic phenotype or with oralcorticosteroid dependent asthma have been established in pediatric patients 6 years of age andolder. Use of DUPIXENT for this indication is supported by evidence from adequate and wellcontrolled studies in adult and pediatric patients 6 years and older [see Clinical Studies (14.2)].
Pediatric Subjects 12 to 17 Years of Age:A total of 107 pediatric subjects 12 to 17 years of age with moderate-to-severe asthma wereenrolled in QUEST and received either 200 mg (N=21) or 300 mg (N=18) DUPIXENT (ormatching placebo either 200 mg [N=34] or 300 mg [N=34]) Q2W. Asthma exacerbations andlung function were assessed in both pediatric subjects 12 to 17 years of age and adults. For boththe 200 mg and 300 mg Q2W doses, improvements in FEV1 (LS mean change from baseline at
Week 12) were observed (0.36 L and 0.27 L, respectively). For the 200 mg Q2W dose, subjects
had a reduction in the rate of severe exacerbations that was consistent with adults. Dupilumab
exposure was higher in pediatric subjects 12 to 17 years of age than that in adults at therespective dose level which was mainly accounted for by difference in body weight [see ClinicalPharmacology (12.3)].
The adverse event profile in pediatric subjects 12 to 17 years of age was generally similar to theadults [see Adverse Reactions (6.1)].
Pediatric Subjects 6 to 11 Years of Age:A total of 408 pediatric subjects 6 to 11 years of age with moderate-to-severe asthma wereenrolled in VOYAGE, which evaluated doses of 100 mg Q2W or 200 mg Q2W. Improvement inasthma exacerbations and lung function were demonstrated [see Clinical Studies (14.2)]. The
effectiveness of DUPIXENT 300 mg Q4W in subjects 6 to 11 years of age with body weight 15
to <30 kg was extrapolated from efficacy of 100 mg Q2W in VOYAGE with support from
population pharmacokinetic analyses showing higher drug exposure levels with 300 mg Q4W[see Clinical Pharmacology (12.3)]. Subjects who completed the treatment period of the
VOYAGE study could participate in the open-label extension study (LTS14424). Eighteen
subjects (≥15 to <30 kg) out of 365 subjects were exposed to 300 mg Q4W in this study, and thesafety profile in these eighteen subjects was consistent with that seen in VOYAGE. Additionalsafety for DUPIXENT 300 mg Q4W is based upon available safety information from thepediatric AD indication [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].
Safety and effectiveness in pediatric patients younger than 6 years of age with asthma have notbeen established.
CRSwNP
The safety and effectiveness of DUPIXENT for add-on maintenance treatment in patients withinadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP) have been
established in pediatric patients aged 12 years and older. Use of DUPIXENT for this indication is
supported by evidence from adequate and well-controlled studies of DUPIXENT as add-on

Page 21 of 57

maintenance treatment in adults with inadequately controlled CRSwNP (SINUS-24 and SINUS52) with the following additional data:Pharmacokinetic (PK) data from adult and pediatric patients aged 12 years and older withmoderate-to-severe asthma and adult patients with inadequately controlled CRSwNP

Safety data in pediatric patients aged 12 years and older with moderate-to-severe asthma[see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.3)]

Safety and effectiveness in pediatric patients younger than 12 years of age with CRSwNP havenot been established.
EoE
The safety and effectiveness of DUPIXENT for the treatment of EoE have been established inpediatric subjects 1 year of age and older, weighing at least 15 kg. Use of DUPIXENT in thispopulation is supported by an adequate well-controlled study in adults and 72 pediatric subjects
12 to 17 years of age (Study EoE-1), a clinical study in 61 pediatric subjects 1 to 11 years of age(Study EoE-2), and pharmacokinetic data in adult and pediatric subjects 1 to 17 years of age. The
safety of DUPIXENT in pediatric subjects 1 to 17 years of age was similar to adults [see Adverse
Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.4)].
Safety and effectiveness in pediatric patients younger than 1 year of age, or weighing less than
15 kg, with EoE have not been established.
Prurigo Nodularis
Safety and effectiveness in pediatric patients younger than 18 years of age with PN have notbeen established.

8.5

Geriatric Use

Of the 1539 subjects with AD exposed to DUPIXENT in a dose-ranging study and placebocontrolled trials, 70 subjects were 65 years or older. Clinical trials of DUPIXENT in AD did notinclude sufficient numbers of subjects aged 65 years and over to determine whether they responddifferently from younger subjects [see Clinical Pharmacology (12.3)].
Of the 1977 subjects with asthma exposed to DUPIXENT, a total of 240 subjects were 65 years
or older. Efficacy and safety in this age group was similar to the overall study population.
Of the 440 subjects with CRSwNP exposed to DUPIXENT, a total of 79 subjects were 65 years
or older. Efficacy and safety in this age group were similar to the overall study population.
Clinical studies of DUPIXENT in EoE did not include sufficient numbers of subjects aged 65
years and over to determine whether they respond differently from younger adult subjects.
Of the 152 subjects with PN exposed to DUPIXENT, a total of 37 were 65 years or older
including 8 subjects 75 years or older. Clinical trials did not include a sufficient number ofsubjects 65 years of age and older to determine whether they respond differently from younger
adult subjects.

Page 22 of 57

10

OVERDOSAGE

There is no specific treatment for DUPIXENT overdose. In the event of overdosage, contact
Poison Control (1-800-222-1222) for the latest recommendations and monitor the patient for any
signs or symptoms of adverse reactions and institute appropriate symptomatic treatment
immediately.

11

DESCRIPTION

Dupilumab, an interleukin-4 receptor alpha antagonist, is a human monoclonal antibody of the
IgG4 subclass that binds to the IL-4Rα subunit and inhibits IL-4 and IL-13 signaling. Dupilumab
has an approximate molecular weight of 147 kDa.
Dupilumab is produced by recombinant DNA technology in Chinese Hamster Ovary cellsuspension culture.
DUPIXENT (dupilumab) Injection is supplied as a sterile, preservative-free, clear to slightly
opalescent, colorless to pale yellow solution for subcutaneous injection. DUPIXENT is provided
as either a single-dose pre-filled syringe with needle shield or a single-dose pre-filled pen in asiliconized Type-1 clear glass syringe. The needle cap is not made with natural rubber latex.
Each 300 mg pre-filled syringe or pre-filled pen delivers 300 mg dupilumab in 2 mL which also
contains L-arginine hydrochloride (10.5 mg), L-histidine (6.2 mg), polysorbate 80 (4 mg),
sodium acetate (2 mg), sucrose (100 mg), and water for injection, pH 5.9.
Each 200 mg pre-filled syringe or pre-filled pen delivers 200 mg dupilumab in 1.14 mL which
also contains L-arginine hydrochloride (12 mg), L-histidine (3.5 mg), polysorbate 80 (2.3 mg),
sodium acetate (1.2 mg), sucrose (57 mg), and water for injection, pH 5.9.

12

CLINICAL PHARMACOLOGY

12.1

Mechanism of Action

Dupilumab is a human monoclonal IgG4 antibody that inhibits interleukin-4 (IL-4) andinterleukin-13 (IL-13) signaling by specifically binding to the IL-4Rα subunit shared by the IL-4
and IL-13 receptor complexes. Dupilumab inhibits IL-4 signaling via the Type I receptor andboth IL-4 and IL-13 signaling through the Type II receptor.
Inflammation driven by IL-4 and IL-13 is an important component in the pathogenesis ofasthma, AD, CRSwNP, EoE, and PN. Multiple cell types that express IL-4Rα (e.g., mast cells,
eosinophils, macrophages, lymphocytes, epithelial cells, goblet cells) and inflammatory
mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines, chemokines) are involved ininflammation. Blocking IL-4Rα with dupilumab inhibits IL-4 and IL-13 cytokine-induced
inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitricoxide, and IgE. The mechanism of dupilumab action has not been definitively established.

12.2

Pharmacodynamics

Consistent with inhibition of IL-4 and IL-13 signaling, dupilumab treatment decreased certain
biomarkers of inflammation. In asthma subjects, fractional exhaled nitric oxide (FeNO) andcirculating concentrations of eotaxin-3, total IgE, allergen specific IgE, TARC, and periostin
Page 23 of 57

were decreased relative to placebo. Reductions in these biomarkers were comparable for the 300
mg Q2W and 200 mg Q2W regimens. These markers were near maximal suppression after 2
weeks of treatment, except for IgE which declined more slowly. These effects were sustained
throughout treatment. The median percent reduction from baseline in total IgE concentrations
with dupilumab treatments was 52% at Week 24 (DRI12544) and 70% at Week 52 (QUEST).
For FeNO, the mean percent reduction from baseline at Week 2 was 35% and 24% in DRI12544
and QUEST, respectively, and in the overall safety population, the mean FeNO level decreased
to 20 ppb.
Antibody Response to Non-Live Vaccines During DUPIXENT Treatment
In a clinical study, adult subjects with AD were treated once weekly for 16 weeks with 300 mg
of DUPIXENT (twice the recommended dosing frequency). After 12 weeks of administration,subjects received a Tdap vaccine and a meningococcal polysaccharide vaccine. Antibody
responses to tetanus toxoid and serogroup C meningococcal polysaccharide were assessed 4
weeks later. Antibody responses to both tetanus toxoid and serogroup C meningococcal
polysaccharide were similar in DUPIXENT-treated and placebo-treated subjects. Antibody
responses to the other active components of both vaccines were not assessed. Antibody responses
to other non-live vaccines were also not assessed.

12.3

Pharmacokinetics

The pharmacokinetics of dupilumab is similar in subjects with AD, asthma, CRSwNP, EoE and
PN.
Absorption
Following an initial subcutaneous (SC) dose of 600 mg, 400 mg, or 300 mg, dupilumab reachedpeak mean ± SD concentrations (Cmax) of 70.1±24.1 mcg/mL, 41.8±12.4 mcg/mL, or 30.5±9.39
mcg/mL, respectively, by approximately 1 week post dose. Steady-state concentrations wereachieved by Week 16 following the administration of 600 mg starting dose and 300 mg dose
either weekly or Q2W, or 400 mg starting dose and 200 mg dose Q2W, or 300 mg Q2W without
a loading dose. Across clinical trials, the mean ± SD steady-state trough concentrations ranged
from 60.3±35.1 mcg/mL to 80.2±35.3 mcg/mL for 300 mg administered Q2W, from 173±75.9
mcg/mL to 195±71.7 mcg/mL for 300 mg administered weekly, and from 29.2±18.7 to
36.5±22.2 mcg/mL for 200 mg administered Q2W.
The bioavailability of dupilumab following a SC dose is similar between AD, asthma, CRSwNP,
EoE, and PN subjects, ranging between 61% and 64%.
Distribution
The estimated total volume of distribution was approximately 4.8±1.3 L.
Elimination
The metabolic pathway of dupilumab has not been characterized. As a human monoclonal IgG4
antibody, dupilumab is expected to be degraded into small peptides and amino acids via
catabolic pathways in the same manner as endogenous IgG. After the last steady-state dose of
300 mg QW, 300 mg Q2W, 200 mg Q2W, 300 mg Q4W, or 200 mg Q4W dupilumab, themedian times to non-detectable concentration (<78 ng/mL) ranged from 9 to 13 weeks in adults
and pediatric subjects 12 to 17 years of age. Population pharmacokinetic analyses indicate thePage 24 of 57

median times to non-detectable concentration are approximately 1.5 times (up to 19 weeks) and2.5 times (up to 32 weeks) longer in pediatric subjects 6 to 11 years of age and pediatric subjects
6 months to 5 years of age, respectively.
Dose Linearity
Dupilumab exhibited nonlinear target-mediated pharmacokinetics with exposures increasing in agreater than dose-proportional manner. The systemic exposure increased by 30-fold when thedose increased 8-fold following a single dose of dupilumab from 75 mg to 600 mg (i.e., 0.25times to 2-times the recommended dose).
WeightDupilumab trough concentrations were lower in subjects with higher body weight.
Immunogenicity
Development of antibodies to dupilumab was associated with lower serum dupilumab
concentrations. A few subjects who had high antibody titers also had no detectable serum
dupilumab concentrations.
Specific Populations
Age
Based on population pharmacokinetic analysis, age did not affect dupilumab clearance in adults
and in pediatric subjects 6 to 17 years of age. In pediatric subjects 6 months to 5 years of age,clearance increased with age.
Geriatric Patients
In subjects who are 65 years and older, the mean ± SD steady-state trough concentrations ofdupilumab were 69.4±31.4 mcg/mL and 166±62.3 mcg/mL, respectively, for 300 mg
administered Q2W and weekly, and 39.7±21.7 mcg/mL for 200 mg administered Q2W.
Pediatric Patients
Atopic Dermatitis
For pediatric subjects 12 to 17 years of age with AD receiving every other week dosing (Q2W)
with either 200 mg (<60 kg) or 300 mg (≥60 kg), the mean ± SD steady-state troughconcentration of dupilumab was 54.5±27.0 mcg/mL.
For pediatric subjects 6 to 11 years of age with AD receiving every other week dosing (Q2W)
with 200 mg (≥30 kg) or every four week dosing (Q4W) with 300 mg (<30 kg), mean ± SD
steady-state trough concentration was 86.0±34.6 mcg/mL and 98.7±33.2 mcg/mL, respectively.
For pediatric subjects 6 months to 5 years of age with AD receiving every four week dosing(Q4W) with 300 mg (≥15 to <30 kg) or 200 mg (≥5 to <15 kg), the mean ± SD steady-statetrough concentration was 110±42.8 mcg/mL and 109±50.8 mcg/mL, respectively.
AsthmaA total of 107 pediatric subjects 12 to 17 years of age with asthma were enrolled in QUEST. The
mean ± SD steady-state trough concentrations of dupilumab were 107±51.6 mcg/mL and
46.7±26.9 mcg/mL, respectively, for 300 mg or 200 mg administered Q2W.
Page 25 of 57

In VOYAGE, dupilumab pharmacokinetics was investigated in 270 subjects with moderate-tosevere asthma following subcutaneous administration of either 100 mg Q2W (for 91 pediatricsubjects weighing <30 kg) or 200 mg Q2W (for 179 pediatric subjects weighing ≥30 kg). The
mean ± SD steady-state trough concentration was 58.4±28.0 mcg/mL and 85.1±44.9 mcg/mL,
respectively. Simulation of a 300 mg Q4W subcutaneous dose in pediatric subjects 6 to 11 yearsof age with body weight of ≥15 to <30 kg resulted in predicted steady-state troughconcentrations (98.7±41.0 mcg/mL) and average concentrations higher than the observed troughconcentrations and average concentrations of 100 mg Q2W (<30 kg).
CRSwNP
Clinical studies have not been conducted in pediatric patients aged 12 years and older with
CRSwNP. Dupilumab exposures are expected to be comparable between adults and pediatricpatients aged 12 years and older at the recommended dosage for CRSwNP (300 mg every 2
weeks).
Eosinophilic Esophagitis
In Study EoE-1, dupilumab pharmacokinetics were investigated in 35 pediatric subjects 12 to 17
years of age, weighing at least 40 kg, with EoE, receiving 300 mg QW. The mean ± SD steadystate trough concentration of dupilumab was 227±95.3 mcg/mL.
In Study EoE-2 Part A, dupilumab pharmacokinetics were investigated in 20 pediatric subjects 1
to 11 years of age with EoE receiving the following weight-based dosing regimens: ≥15 to <30
kg (200 mg Q2W) and ≥30 to <40 kg (300 mg Q2W). At Week 16, the mean ± SD steady-statetrough concentration of dupilumab was 174±66.2 mcg/mL.
The systemic exposure in pediatric subjects 1 to 11 years of age with a body weight ≥40 kg
receiving 300 mg QW is expected to be comparable to adult and pediatric subjects 12 years andolder with a body weight ≥40 kg. The systemic exposure in pediatric subjects 12 to 17 years ofage with a body weight <40 kg receiving 300 mg Q2W is expected to be comparable to pediatricsubjects 6 to 11 years of age.
Drug Interaction Studies
An effect of dupilumab on the PK of co-administered medications is not expected. Based on the
population analysis, commonly co-administered medications had no effect on DUPIXENT
pharmacokinetics in subjects with moderate-to-severe asthma.
Cytochrome P450 Substrates
The effects of dupilumab on the pharmacokinetics of midazolam (metabolized by CYP3A4),
warfarin (metabolized by CYP2C9), omeprazole (metabolized by CYP2C19), metoprolol(metabolized by CYP2D6), and caffeine (metabolized by CYP1A2) were evaluated in a study
with 12-13 evaluable subjects with AD (a SC loading dose of 600 mg followed by 300 mg SC
weekly for six weeks). No clinically significant changes in AUC were observed. The largest
effect was observed for metoprolol (CYP2D6) with an increase in AUC of 29%.

12.6

Immunogenicity

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity andspecificity of the assay. Differences in assay methods preclude meaningful comparisons of the
Page 26 of 57

incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug
antibodies in other studies, including those of DUPIXENT or of other dupilumab products.
Atopic Dermatitis
Approximately 6% of subjects with AD who received DUPIXENT 300 mg Q2W for 52
weeks developed antibodies to DUPIXENT; approximately 2% exhibited persistent ADA
responses, and approximately 1% had neutralizing antibodies. Similar results were observedin pediatric subjects 6 months to 11 years of age with AD who received either DUPIXENT
200 mg Q2W, 200 mg Q4W, or 300 mg Q4W.
Approximately 16% of pediatric subjects 12 to 17 years of age with AD who received
DUPIXENT 300 mg or 200 mg Q2W for 16 weeks developed antibodies to DUPIXENT;
approximately 3% exhibited persistent ADA responses, and approximately 5% had
neutralizing antibodies.
AsthmaApproximately 5% of subjects with asthma who received DUPIXENT 300 mg Q2W for 52
weeks developed antibodies to DUPIXENT; approximately 2% exhibited persistent ADA
responses, and approximately 2% had neutralizing antibodies. Similar results were observedin pediatric subjects 6 to 11 years of age with asthma who received either DUPIXENT 100
mg Q2W or 200 mg Q2W up to 52 weeks.
Approximately 9% of subjects with asthma who received DUPIXENT 200 mg Q2W for 52
weeks developed antibodies to DUPIXENT; approximately 4% exhibited persistent ADA
responses, and approximately 4% had neutralizing antibodies.
Chronic Rhinosinusitis with Nasal Polyps
Approximately 5% of adult subjects with CRSwNP who received DUPIXENT 300 mg Q2W
for 52 weeks developed antibodies to DUPIXENT; approximately 2% exhibited persistent
ADA responses, and approximately 3% had neutralizing antibodies.
Eosinophilic Esophagitis
Approximately 1% of subjects with EoE who received DUPIXENT 300 mg QW for 52
weeks developed antibodies to DUPIXENT; no subjects exhibited persistent ADA responses
or had neutralizing antibodies. Similar results were observed in pediatric subjects 1 to 11
years of age with EoE administered either DUPIXENT 200 mg Q2W or 300 mg Q2W for 52
weeks.
Prurigo Nodularis
Approximately 8% of subjects with PN who received DUPIXENT 300 mg Q2W for 24
weeks developed antibodies to DUPIXENT; approximately 1% exhibited persistent ADA
responses, and approximately 3% had neutralizing antibodies.
The antibody titers detected in subjects who received DUPIXENT were mostly low. In subjects
who received DUPIXENT, development of high titer antibodies to DUPIXENT was associatedwith lower serum dupilumab concentrations [see Clinical Pharmacology (12.3)].

Page 27 of 57

Two adult subjects with AD who experienced high titer antibody responses developed serum
sickness or serum sickness-like reactions during DUPIXENT therapy [see Warnings andPrecautions (5.1)].

13

NONCLINICAL TOXICOLOGY

13.1

Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of
dupilumab.
No effects on fertility parameters such as reproductive organs, menstrual cycle length, or sperm
analysis were observed in sexually mature mice that were subcutaneously administered ahomologous antibody against IL-4Rα at doses up to 200 mg/kg/week.

14

CLINICAL STUDIES

14.1

Atopic Dermatitis

Adults with Atopic Dermatitis
Three randomized, double-blind, placebo-controlled trials (SOLO 1 (NCT02277743), SOLO 2(NCT02277769), and CHRONOS (NCT02260986)) enrolled a total of 2119 adult subjects 18
years of age and older with moderate-to-severe AD not adequately controlled by topical
medication(s). Disease severity was defined by an Investigator’s Global Assessment (IGA) score≥3 in the overall assessment of AD lesions on a severity scale of 0 to 4, an Eczema Area andSeverity Index (EASI) score ≥16 on a scale of 0 to 72, and a minimum body surface area
involvement of ≥10%. At baseline, 59% of subjects were male, 67% were White, 52% ofsubjects had a baseline IGA score of 3 (moderate AD), and 48% of subjects had a baseline IGAof 4 (severe AD). The baseline mean EASI score was 33 and the baseline weekly averaged Peak
Pruritus Numeric Rating Scale (NRS) was 7 on a scale of 0-10.
In all three trials, subjects in the DUPIXENT group received subcutaneous injections of
DUPIXENT 600 mg at Week 0, followed by 300 mg every other week (Q2W). In themonotherapy trials (SOLO 1 and SOLO 2), subjects received DUPIXENT or placebo for 16
weeks.
In the concomitant therapy trial (CHRONOS), subjects received DUPIXENT or placebo withconcomitant topical corticosteroids (TCS) and as needed topical calcineurin inhibitors forproblem areas only, such as the face, neck, intertriginous and genital areas for 52 weeks.
All three trials assessed the primary endpoint, the change from baseline to Week 16 in the
proportion of subjects with an IGA 0 (clear) or 1 (almost clear) and at least a 2-point
improvement. Other endpoints included the proportion of subjects with EASI-75 (improvementof at least 75% in EASI score from baseline), and reduction in itch as defined by at least a 4point improvement in the Peak Pruritus NRS from baseline to Week 16.
Clinical Response at Week 16 (SOLO 1, SOLO 2, and CHRONOS)
The results of the DUPIXENT monotherapy trials (SOLO 1 and SOLO 2) and the DUPIXENTwith concomitant TCS trial (CHRONOS) are presented in Table 11.
Page 28 of 57

Table 11:

Efficacy Results of DUPIXENT with or without Concomitant TCS at Week
16 (FAS) in Adult Subjects 18 Years of Age and Older with Moderate-toSevere AD
SOLO 1
DUPIXENT
Placebo
300 mg Q2W

SOLO 2
DUPIXENT Placebo
300 mg
Q2W

CHRONOSDUPIXENT
Placebo
300 mg Q2W
+ TCS
+ TCS

Number of subjects
224
224
233
236
106
315
randomized (FAS)a
IGA 0 or 1b,c
38%
10%
36%
9%
39%
12%
EASI-75c
51%
15%
44%
12%
69%
23%
EASI-90c
36%
8%
30%
7%
40%
11%
Number of subjects withbaseline Peak Pruritus
213
212
225
221
102
299
NRS score ≥4
Peak Pruritus NRS
41%
12%
36%
10%
59%
20%
(≥4-point improvement)ca
Full Analysis Set (FAS) includes all subjects randomized.
bResponder was defined as a subject with an IGA 0 or 1 (“clear” or “almost clear”) and a reduction of ≥2 points on
a 0-4 IGA scale.
cSubjects who received rescue treatment or with missing data were considered as non-responders.

Figure 1:

Proportion of Adult Subjects 18 Years of Age and Older with Moderate-toSevere AD with ≥4-point Improvement on the Peak Pruritus NRS in SOLO
1a and SOLO 2a Studies (FAS)b
SOLO 1SOLO 2a

In the primary analyses of the efficacy endpoints, subjects who received rescue treatment or with missing data
were considered non-responders.
bFull Analysis Set (FAS) includes all subjects randomized.

In CHRONOS, of the 421 subjects, 353 had been on study for 52 weeks at the time of data
analysis. Of these 353 subjects, responders at Week 52 represent a mixture of subjects who
maintained their efficacy from Week 16 (e.g., 53% of DUPIXENT IGA 0 or 1 responders at
Week 16 remained responders at Week 52) and subjects who were non-responders at Week 16
who later responded to treatment (e.g., 24% of DUPIXENT IGA 0 or 1 non-responders at Week
Page 29 of 57

16 became responders at Week 52). Results of supportive analyses of the 353 subjects in the
DUPIXENT with concomitant TCS trial (CHRONOS) are presented in Table 12.
Table 12:

Efficacy Results (IGA 0 or 1) of DUPIXENT with Concomitant TCS at Week
16 and 52 in Adult Subjects 18 Years of Age and Older with Moderate-toSevere AD

DUPIXENT
Placebo + TCS
300 mg Q2W + TCS
Number of Subjectsa
89
264
Responderb,c at Week 16 and 52
22%
7%
Responder at Week 16 but Non-responder at Week 52
20%
7%
Non-responder at Week 16 and Responder at Week 52
13%
6%
Non-responder at Week 16 and 52
44%
80%
Overall Responderb,c Rate at Week 52
36%
13%
a
In CHRONOS, of the 421 randomized and treated subjects, 68 subjects (16%) had not been on study for 52 weeks
at the time of data analysis.
b
Responder was defined as a subject with an IGA 0 or 1 (“clear” or “almost clear”) and a reduction of ≥2 points on
a 0-4 IGA scale.
cSubjects who received rescue treatment or with missing data were considered as non-responders.

Treatment effects in subgroups (weight, age, gender, race, and prior treatment, including
immunosuppressants) in SOLO 1, SOLO 2, and CHRONOS were generally consistent with theresults in the overall study population.
In SOLO 1, SOLO 2, and CHRONOS, a third randomized treatment arm of DUPIXENT 300 mg
QW did not demonstrate additional treatment benefit over DUPIXENT 300 mg Q2W.
Subjects in SOLO 1 and SOLO 2 who had an IGA 0 or 1 with a reduction of ≥2 points were rerandomized into SOLO CONTINUE (NCT02395133). SOLO CONTINUE evaluated multiple
DUPIXENT monotherapy dose regimens for maintaining treatment response. The study included
subjects randomized to continue with DUPIXENT 300 mg Q2W (62 subjects) or switch toplacebo (31 subjects) for 36 weeks. IGA 0 or 1 responses at Week 36 were as follows: 33 (53%)
in the Q2W group and 3 (10%) in the placebo group.
Pediatric Subjects 12 to 17 Years of Age with Atopic Dermatitis
The efficacy of DUPIXENT monotherapy in pediatric subjects 12 to 17 years of age was
evaluated in a multicenter, randomized, double-blind, placebo-controlled trial (AD-1526;
NCT03054428) in 251 pediatric subjects 12 to 17 years of age, with moderate-to-severe AD
defined by an IGA score ≥3 (scale of 0 to 4), an EASI score ≥16 (scale of 0 to 72), and aminimum BSA involvement of ≥10%. Eligible subjects enrolled into this trial had previous
inadequate response to topical medication.
Subjects in the DUPIXENT group with baseline weight of <60 kg received an initial dose of 400
mg at Week 0, followed by 200 mg Q2W for 16 weeks. Subjects with baseline weight of ≥60 kg
received an initial dose of 600 mg at Week 0, followed by 300 mg Q2W for 16 weeks. Subjects
were permitted to receive rescue treatment at the discretion of the investigator. Subjects who
received rescue treatment were considered non-responders.
In AD-1526, the mean age was 14.5 years, the median weight was 59.4 kg, 41% of subjects werefemale, 63% were White, 15% were Asian, and 12% were Black. At baseline, 46% of subjects
had an IGA score of 3 (moderate AD), 54% had an IGA score of 4 (severe AD), the mean BSA
Page 30 of 57

involvement was 57%, and 42% had received prior systemic immunosuppressants. Also, atbaseline, the mean EASI score was 36, and the weekly averaged Peak Pruritus NRS was 8 on ascale of 0-10. Overall, 92% of subjects had at least one co-morbid allergic condition; 66% hadallergic rhinitis, 54% had asthma, and 61% had food allergies.
The primary endpoint was the proportion of subjects with an IGA 0 (clear) or 1 (almost clear)
and at least a 2-point improvement from baseline to Week 16. Other evaluated outcomes
included the proportion of subjects with EASI-75 or EASI-90 (improvement of at least 75% or
90% in EASI from baseline, respectively), and reduction in itch as measured by the Peak Pruritus
NRS (≥4-point improvement).
The efficacy results at Week 16 for AD-1526 are presented in Table 13.
Table 13:

Efficacy Results of DUPIXENT in AD-1526 at Week 16 (FAS)a in PediatricSubjects 12 to 17 Years of Age with Moderate-to-Severe AD

DUPIXENTd
Placebo
200 mg (<60 kg) or 300 mg (≥60 kg) Q2W
N=85a
a
N=82
IGA 0 or 1b,c
24%
2%
EASI-75c
42%
8%
EASI-90c
23%
2%
Peak Pruritus NRS (≥4-point improvement)c37%
5%aFull Analysis Set (FAS) includes all subjects randomized.
bResponder was defined as a subject with an IGA 0 or 1 (“clear” or “almost clear”) and a reduction of ≥2 points on
a 0-4 IGA scale.
cSubjects who received rescue treatment or with missing data were considered as non-responders (59% and 21% in
the placebo and DUPIXENT arms, respectively).
d
At Week 0, subjects received 400 mg (baseline weight <60 kg) or 600 mg (baseline weight ≥60 kg) of
DUPIXENT.

A greater proportion of subjects randomized to DUPIXENT achieved an improvement in thePeak Pruritus NRS compared to placebo (defined as ≥4-point improvement at Week 4). See
Figure 2.

Page 31 of 57

Figure 2:

Proportion of Pediatric Subjects 12 to 17 Years of Age with Moderate-toSevere AD with ≥4-point Improvement on the Peak Pruritus NRS in AD1526a (FAS)ba

In the primary analyses of the efficacy endpoints, subjects who received rescue treatment or with missing data
were considered non-responders.
bFull Analysis Set (FAS) includes all subjects randomized.

Pediatric Subjects 6 to 11 Years of Age with Atopic Dermatitis
The efficacy and safety of DUPIXENT use concomitantly with TCS in pediatric subjects wasevaluated in a multicenter, randomized, double-blind, placebo-controlled trial (AD-1652;
NCT03345914) in 367 subjects 6 to 11 years of age, with AD defined by an IGA score of 4
(scale of 0 to 4), an EASI score ≥21 (scale of 0 to 72), and a minimum BSA involvement of≥15%. Eligible subjects enrolled into this trial had previous inadequate response to topical
medication. Enrollment was stratified by baseline weight (<30 kg; ≥30 kg).
Subjects in the DUPIXENT Q4W + TCS group received an initial dose of 600 mg on Day 1,
followed by 300 mg Q4W from Week 4 to Week 12, regardless of weight. Subjects in the
DUPIXENT Q2W + TCS group with baseline weight of <30 kg received an initial dose of 200
mg on Day 1, followed by 100 mg Q2W from Week 2 to Week 14, and subjects with baseline
weight of ≥30 kg received an initial dose of 400 mg on Day 1, followed by 200 mg Q2W from
Week 2 to Week 14. Subjects were permitted to receive rescue treatment at the discretion of theinvestigator. Subjects who received rescue treatment were considered non-responders.
In AD-1652, the mean age was 8.5 years, the median weight was 29.8 kg, 50% of subjects werefemale, 69% were White, 17% were Black, and 8% were Asian. At baseline, the mean BSA
involvement was 58%, and 17% had received prior systemic non-steroidal immunosuppressants.
Also, at baseline the mean EASI score was 37.9, and the weekly average of daily worst itch score
was 7.8 on a scale of 0-10. Overall, 92% of subjects had at least one co-morbid allergic
condition; 64% had food allergies, 63% had other allergies, 60% had allergic rhinitis, and 47%
had asthma.
The primary endpoint was the proportion of subjects with an IGA 0 (clear) or 1 (almost clear) at
Week 16. Other evaluated outcomes included the proportion of subjects with EASI-75 or EASIPage 32 of 57

90 (improvement of at least 75% or 90% in EASI from baseline, respectively), and reduction initch as measured by the Peak Pruritus NRS (≥4-point improvement).
Table 14 presents the results by baseline weight strata for the approved dose regimens.
Table 14:

Efficacy Results of DUPIXENT with Concomitant TCS in AD-1652 at Week
16 (FAS)a in Pediatric Subjects 6 to 11 Years of Age with AD
DUPIXENT
300 mg Q4Wd
+ TCS
(N=61)<30 kgPlacebo+ TCS(N=61)<30 kg

DUPIXENT
200 mg Q2We
+ TCS
(N=59)≥30 kgPlacebo+ TCS(N=62)≥30 kg

IGA 0 or 1b,c
30%
13%
39%
10%
EASI-75c
75%
28%
75%
26%
c
EASI-90
46%
7%
36%
8%
Peak Pruritus NRS (≥4-point improvement)c
54%
12%
61%
13%
a
Full Analysis Set (FAS) includes all subjects randomized.
bResponder was defined as a subject with an IGA 0 or 1 (“clear” or “almost clear”).
cSubjects who received rescue treatment or with missing data were considered as non-responders.
d
At Day 1, subjects received 600 mg of DUPIXENT.
eAt Day 1, subjects received 200 mg (baseline weight <30 kg) or 400 mg (baseline weight ≥30 kg) of DUPIXENT.

A greater proportion of subjects randomized to DUPIXENT + TCS achieved an improvement in
the Peak Pruritus NRS compared to placebo + TCS (defined as ≥4-point improvement at
Week 16). See Figure 3.
Figure 3:

Proportion of Pediatric Subjects 6 to 11 Years of Age with AD with ≥4-point
Improvement on the Peak Pruritus NRS at Week 16 in AD-1652a (FAS)ba

In the primary analyses of the efficacy endpoints, subjects who received rescue treatment or with missing data
were considered non-responders.
bFull Analysis Set (FAS) includes all subjects randomized.

Pediatric Subjects 6 Months to 5 Years of Age with Atopic Dermatitis
The efficacy and safety of DUPIXENT use concomitantly with TCS in pediatric subjects wasevaluated in a multicenter, randomized, double-blind, placebo-controlled trial (AD-1539;
NCT03346434) in 162 subjects 6 months to 5 years of age, with moderate-to-severe AD definedPage 33 of 57

by an IGA score ≥3 (scale of 0 to 4), an EASI score ≥16 (scale of 0 to 72), and a minimum BSA
involvement of ≥10%. Eligible subjects enrolled into this trial had previous inadequate response
to topical medication. Enrollment was stratified by baseline weight (≥5 to <15 kg and ≥15 to <30kg).
Subjects in the DUPIXENT Q4W + TCS group with baseline weight of ≥5 to <15 kg received an
initial dose of 200 mg on Day 1, followed by 200 mg Q4W from Week 4 to Week 12, andsubjects with baseline weight of ≥15 to <30 kg received an initial dose of 300 mg on Day 1,
followed by 300 mg Q4W from Week 4 to Week 12. Subjects were permitted to receive rescue
treatment at the discretion of the investigator. Subjects who received rescue treatment wereconsidered non-responders.
In AD-1539, the mean age was 3.8 years, the median weight was 16.5 kg, 39% of subjects werefemale, 69% were White, 19% were Black, and 6% were Asian. At baseline, the mean BSA
involvement was 58%, and 29% of subjects had received prior systemic immunosuppressants.
Also, at baseline the mean EASI score was 34.1, and the weekly average of daily worst
scratch/itch score was 7.6 on a scale of 0-10. Overall, 81.4% of subjects had at least one comorbid allergic condition; 68.3% had food allergies, 52.8% had other allergies, 44.1% hadallergic rhinitis, and 25.5% had asthma.
The primary endpoint was the proportion of subjects with an IGA 0 (clear) or 1 (almost clear) at
Week 16. Other evaluated outcomes included the proportion of subjects with EASI-75 or EASI90 (improvement of at least 75% or 90% in EASI from baseline, respectively), and reduction initch as measured by the Worst Scratch/Itch NRS (≥4-point improvement).
The efficacy results at Week 16 for AD-1539 are presented in Table 15.
Table 15:

Efficacy Results of DUPIXENT with Concomitant TCS in AD-1539 at Week
16 (FAS)a in Pediatric Subjects 6 Months to 5 Years of Age with Moderateto-Severe AD

b,c

DUPIXENT+ TCS
200 mg (5 to <15 kg) or
300 mg (15 to <30 kg)
Q4Wd(N=83)a
28%
53%
25%
48%

Placebo+ TCS

Difference vs. Placebo (95 % CI)(N=79)a
4%
11%
3%
9%

IGA 0 or 1
24% (13%, 34%)
EASI-75c
42% (29%, 55%)c
EASI-9023% (12%, 33%)
Worst Scratch/Itch NRS (≥4-point
39% (26%, 52%)
improvement)c
CI = confidence intervalaFull Analysis Set (FAS) includes all subjects randomized.
bResponder was defined as a subject with an IGA 0 or 1 (“clear” or “almost clear”).
cSubjects who received rescue treatment (63% and 19% in the placebo and DUPIXENT arms, respectively) or withmissing data were considered as non-responders.
d
At Day 1, subjects received 200 mg (5 to <15 kg) or 300 mg (15 to <30 kg) of DUPIXENT.

Atopic Dermatitis with Hand and/or Foot Involvement
The efficacy and safety of DUPIXENT was evaluated in a 16-week, multicenter, randomized,
double-blind, parallel-group, placebo-controlled trial (Liberty-AD-HAFT; NCT04417894) inPage 34 of 57

133 adult and pediatric subjects 12 to 17 years of age with atopic dermatitis with moderate-tosevere hand and/or foot involvement, defined by an established diagnosis of atopic dermatitis
and screening to rule out irritant and allergic contact dermatitis through history and appropriate
patch testing, and by an IGA (hand and foot) score ≥3 (scale of 0 to 4) and a hand and foot Peak
Pruritus Numeric Rating Scale (NRS) score for maximum itch intensity ≥4 (scale of 0 to 10).
Fifty-three (53) percent (N=70/133) of the subjects also had moderate-to-severe AD outside of
the hands or feet (IGA global ≥3). Eligible subjects had previous inadequate response or
intolerance to treatment of hand and/or foot dermatitis with topical AD medications. In this trial
67 subjects received DUPIXENT, and 66 subjects received placebo. DUPIXENT-treatedsubjects received the recommended dosage based on their age and body weight [see Dosage andAdministration (2.3)]. Subjects were not allowed concomitant use of topical treatments for AD
on the hands and feet during the trial, but were allowed the use of topical treatments for AD onother parts of the body with certain restrictions.
In Liberty-AD-HAFT, 38% of subjects were male, 80% were White, 13% were Asian, and 5%
were Black or African American. For ethnicity, 4% were identified as Hispanic or Latino and
96% were identified as not Hispanic or Latino. Seventy-two (72) percent (N=96/133) of subjects
had a baseline IGA (hand and foot) score of 3 (atopic dermatitis with moderate hand and/or footinvolvement), and 28% (N=37/133) of subjects had a baseline IGA (hand and foot) score of
4 (atopic dermatitis with severe hand and/or foot involvement). The baseline weekly averaged
hand and foot Peak Pruritus NRS score was 7.1.
The primary endpoint was the proportion of subjects with an IGA hand and foot score of 0(clear) or 1 (almost clear) at Week 16. The key secondary endpoint was reduction of itch asmeasured by the hand and foot Peak Pruritus NRS (≥4-point improvement).
The efficacy results at Week 16 for Liberty-AD-HAFT are presented in Table 16.
Table 16:

Efficacy Results of DUPIXENT in Liberty-AD-HAFT at Week 16 (FAS)a in
Adult and Pediatric Subjects 12 to 17 Years of Age with AD with Moderateto-Severe Hand and/or Foot Involvement

b,c

DUPIXENT
200/300 mg Q2Wd
(N=67)a40%
52%

Placebo

Difference vs. Placebo (95 % CI)(N=66)a17%
14%

IGA (hand and foot) 0 or 1
24% (9%, 38%)
Improvement (reduction) of
39% (24%, 53%)
weekly averaged hand and footPeak Pruritus NRS ≥4c
CI = confidence intervalaFull Analysis Set (FAS) includes all subjects randomized.
bResponder was defined as a subject with an IGA 0 or 1 (“clear” or “almost clear”).
cSubjects who received rescue treatment (21% and 3% in the placebo and DUPIXENT arms, respectively) or withmissing data were considered as non-responders.
dAdults received a loading dose of DUPIXENT 600 mg SC followed by 300 mg SC Q2W. Pediatric subjects 12 to
17 years of age received a loading dose of DUPIXENT 600 mg SC followed by 300 mg SC Q2W (for body weight≥60 kg) or a loading dose of DUPIXENT 400 mg SC followed by 200 mg SC Q2W (for body weight <60 kg).

14.2

Asthma

The asthma development program for patients aged 12 years and older included threerandomized, double-blind, placebo-controlled, parallel-group, multicenter trials (DRI12544
Page 35 of 57

(NCT01854047), QUEST (NCT02414854), and VENTURE (NCT02528214)) of 24 to 52 weeks
in treatment duration which enrolled a total of 2888 subjects. Subjects enrolled in DRI12544 and
QUEST were required to have a history of 1 or more asthma exacerbations that required
treatment with systemic corticosteroids or emergency department visit or hospitalization for thetreatment of asthma in the year prior to trial entry. Subjects enrolled in VENTURE required
dependence on daily oral corticosteroids in addition to regular use of high-dose inhaledcorticosteroids plus an additional controller(s). In all 3 trials, subjects were enrolled without
requiring a minimum baseline blood eosinophil count. In QUEST and VENTURE, subjects withscreening blood eosinophil level of >1500 cells/mcL (<1.3%) were excluded. DUPIXENT was
administered as add-on to background asthma treatment. Subjects continued background asthma
therapy throughout the duration of the studies, except in VENTURE in which OCS dose wastapered as described below.
DRI12544
DRI12544 was a 24-week dose-ranging study which included 776 adult subjects (18 years of age
and older). DUPIXENT compared with placebo was evaluated in adult subjects with moderateto-severe asthma on a medium or high-dose inhaled corticosteroid and a long acting beta agonist.
Subjects were randomized to receive either 200 mg (N=150) or 300 mg (N=157) DUPIXENT
every other week (Q2W) or 200 mg (N=154) or 300 mg (N=157) DUPIXENT every 4 weeks
following an initial dose of 400 mg, 600 mg or placebo (N=158), respectively. The primary
endpoint was mean change from baseline to Week 12 in FEV1 (L) in subjects with baseline blood
eosinophils ≥300 cells/mcL. Other endpoints included percent change from baseline in FEV1 andannualized rate of severe asthma exacerbation events during the 24-week placebo-controlled
treatment period. Results were evaluated in the overall population and subgroups based on
baseline blood eosinophil count (≥300 cells/mcL and <300 cells/mcL). Additional secondary
endpoints included responder rates in the patient reported Asthma Control Questionnaire (ACQ5) and Asthma Quality of Life Questionnaire, Standardized Version (AQLQ(S)) scores.
QUEST
QUEST was a 52-week study which included 1902 adult and pediatric subjects (12 years of age
and older). DUPIXENT compared with placebo was evaluated in 107 pediatric subjects 12 to 17
years of age and 1795 adult subjects with moderate-to-severe asthma on a medium or high-dose
inhaled corticosteroid (ICS) and a minimum of one and up to two additional controller
medications. Subjects were randomized to receive either 200 mg (N=631) or 300 mg (N=633)
DUPIXENT Q2W (or matching placebo for either 200 mg [N=317] or 300 mg [N=321] Q2W)
following an initial dose of 400 mg, 600 mg or placebo, respectively. The primary endpoints
were the annualized rate of severe exacerbation events during the 52-week placebo-controlled
period and change from baseline in pre-bronchodilator FEV1 at Week 12 in the overall
population (unrestricted by minimum baseline blood eosinophils count). Additional secondary
endpoints included annualized severe exacerbation rates and FEV1 in subjects with different
baseline levels of blood eosinophils as well as responder rates in the ACQ-5 and AQLQ(S)scores.
VENTUREVENTURE was a 24-week oral corticosteroid-reduction study in 210 adult and pediatric subjects
15 years of age and older with asthma who required daily oral corticosteroids in addition to
Page 36 of 57

regular use of high dose inhaled corticosteroids plus an additional controller. After optimizing
the OCS dose during the screening period, subjects received 300 mg DUPIXENT (N=103) orplacebo (N=107) once Q2W for 24 weeks following an initial dose of 600 mg or placebo.
Subjects continued to receive their existing asthma medicine during the study; however, their
OCS dose was reduced every 4 weeks during the OCS reduction phase (Week 4-20), as long asasthma control was maintained. The primary endpoint was the percent reduction of oralcorticosteroid dose at Weeks 20 to 24 compared with the baseline dose, while maintaining
asthma control in the overall population (unrestricted by minimum baseline blood eosinophils
count). Additional secondary endpoints included the annualized rate of severe exacerbation
events during treatment period and responder rate in the ACQ-5 and AQLQ(S) scores.
The demographics and baseline characteristics of these 3 trials are provided in Table 17 below.
Table 17:

Demographics and Baseline Characteristics of Asthma Trials
Parameter

Mean age (years) (SD)% Female% WhiteDuration of Asthma (years), mean (± SD)
Never smoked (%)
Mean exacerbations in previous year (± SD)
High dose ICS use (%)
Pre-dose FEV1 (L) at baseline (± SD)
Mean percent predicted FEV1 at baseline (%)(± SD)% Reversibility (± SD)
Atopic Medical History % Overall(AD %, NP %, AR %)DRI12544(N=776)49 (13)63
78
22 (15)77
2.2 (2.1)
50
1.84 (0.54)
61 (11)QUEST(N=1902)48 (15)63
83
21 (15)81
2.1 (2.2)
52
1.78 (0.60)
58 (14)

VENTURE(N=210)51 (13)61
94
20 (14)81
2.1 (2.2)
89
1.58 (0.57)
52 (15)27 (15)73(8, 11, 62)

26 (22)
78(10, 13, 69)

19 (23)72(8, 21, 56)

Mean FeNO ppb (± SD)
39 (35)35 (33)38 (31)
Mean total IgE IU/mL (± SD)
435 (754)
432 (747)
431 (776)
Mean baseline blood Eosinophil count350 (430)
360 (370)
350 (310)(± SD) cells/mcL
ICS = inhaled corticosteroid; FEV1 = Forced expiratory volume in 1 second; AD = atopic dermatitis; NP = nasal
polyps; AR = allergic rhinitis; FeNO = fraction of exhaled nitric oxide

Exacerbations
DRI12544 and QUEST evaluated the frequency of severe asthma exacerbations defined asdeterioration of asthma requiring the use of systemic corticosteroids for at least 3 days or
hospitalization or emergency room visit due to asthma that required systemic corticosteroids. In
the primary analysis population (subjects with baseline blood eosinophil count of ≥300 cells/mcL
in DRI12544 and the overall population in QUEST), subjects receiving either DUPIXENT 200
mg or 300 mg Q2W had significant reductions in the rate of asthma exacerbations compared toplacebo. In the overall population in QUEST, the rate of severe exacerbations was 0.46 and 0.52
for DUPIXENT 200 mg Q2W and 300 mg Q2W, respectively, compared to matched placebo
rates of 0.87 and 0.97. The rate ratio of severe exacerbations compared to placebo was 0.52 (95%
CI: 0.41, 0.66) and 0.54 (95% CI: 0.43, 0.68) for DUPIXENT 200 mg Q2W and 300 mg Q2W,
respectively. Results in subjects with baseline blood eosinophil counts ≥300 cells/mcL in
DRI12544 and QUEST are shown in Table 18.
Page 37 of 57

Response rates by baseline blood eosinophils and baseline FeNO for QUEST are shown for theoverall population in Figure 4 and Figure 5, respectively. Elevation of FeNO can be a marker ofthe eosinophilic asthma phenotype when supported by clinical data. Pre-specified subgroup
analyses of DRI12544 and QUEST demonstrated that there were greater reductions in severe
exacerbations in subjects with higher baseline blood eosinophil levels (≥150 cells/mcL) or FeNO(≥25 ppb). In QUEST, reductions in exacerbations were significant in the subgroup of subjects
with baseline blood eosinophils ≥150 cells/mcL. In subjects with baseline blood eosinophil count<150 cells/mcL and FeNO <25 ppb, similar severe exacerbation rates were observed between
DUPIXENT and placebo.
In QUEST, the estimated rate ratio of exacerbations leading to hospitalizations and/or emergency
room visits versus placebo was 0.53 (95% CI: 0.28, 1.03) and 0.74 (95% CI: 0.32, 1.70) with
DUPIXENT 200 mg or 300 mg Q2W, respectively.
Table 18:
Trial

Rate of Severe Exacerbations in DRI12544 and QUEST
Treatment
N

DRI12544

QUEST

DUPIXENT
200 mg Q2W
DUPIXENT
300 mg Q2W
Placebo65

DUPIXENT
200 mg Q2W
Placebo264

DUPIXENT
300 mg Q2W
Placebo

64
68

148
277
142

Baseline Blood EOS ≥300 cells/mcL(primary analysis population, DRI12544)
Rate
Rate Ratio(95% CI)(95% CI)
0.30
0.29(0.13, 0.68)(0.11, 0.76)
0.20
0.19
(0.08, 0.52)(0.07, 0.56)
1.04(0.57, 1.90)
0.37
0.34
(0.29, 0.48)(0.24, 0.48)
1.08(0.85, 1.38)
0.40
0.33
(0.32, 0.51)(0.23, 0.45)
1.24(0.97, 1.57)

Page 38 of 57

Figure 4:

Relative Risk in Annualized Event Rate of Severe Exacerbations acrossBaseline Blood Eosinophil Count (cells/mcL) in Subjects with Moderate-toSevere Asthma (QUEST)

Figure 5:

Relative Risk in Annualized Event Rate of Severe Exacerbations acrossBaseline FeNO Group (ppb) in Subjects with Moderate-to-Severe Asthma(QUEST)

The time to first exacerbation was longer for the subjects receiving DUPIXENT compared toplacebo in QUEST (Figure 6).

Page 39 of 57

Figure 6:

Kaplan Meier Incidence Curve for Time to First Severe Exacerbation in
Subjects with Moderate-to-Severe Asthma with Baseline Blood Eosinophils≥300 cells/mcL (QUEST)aa

At the time of the database lock, not all subjects had completed Week 52

Lung Function
Significant increases in pre-bronchodilator FEV1 were observed at Week 12 for DRI12544 and
QUEST in the primary analysis populations (subjects with baseline blood eosinophil count of≥300 cells/mcL in DRI12544 and the overall population in QUEST). In the overall population in
QUEST, the FEV1 LS mean change from baseline was 0.32 L (21%) and 0.34 L (23%) for
DUPIXENT 200 mg Q2W and 300 mg Q2W, respectively, compared to matched placebo meansof 0.18 L (12%) and 0.21 L (14%). The mean treatment difference versus placebo was 0.14 L(95% CI: 0.08, 0.19) and 0.13 L (95% CI: 0.08, 0.18) for DUPIXENT 200 mg Q2W and 300 mg
Q2W, respectively. Results in subjects with baseline blood eosinophil counts ≥300 cells/mcL in
DRI12544 and QUEST are shown in Table 19.
Improvements in FEV1 by baseline blood eosinophils and baseline FeNO for QUEST are shownin Figure 7 and 8, respectively. Subgroup analysis of DRI12544 and QUEST demonstrated
greater improvement in subjects with higher baseline blood eosinophils (≥150 cells/mcL) or
FeNO (≥25 ppb). In subjects with baseline blood eosinophil count <150 cells/mcL and FeNO
<25 ppb, similar differences in FEV1 were observed between DUPIXENT and placebo.
Mean changes in FEV1 over time in QUEST are shown in Figure 9.

Page 40 of 57

Table 19:

Trial

Mean Change from Baseline and Difference vs Placebo in PreBronchodilator FEV1 at Week 12 in Subjects with Moderate-to-Severe
Asthma (DRI12544 and QUEST)
Treatment
N

DRI12544

QUEST

Figure 7:

DUPIXENT
200 mg Q2W
DUPIXENT
300 mg Q2W
Placebo
DUPIXENT
200 mg Q2W
Placebo
DUPIXENT
300 mg Q2W
Placebo

65
64
68
264
148
277
142

Baseline Blood EOS ≥300 cells/mcL(primary analysis population, DRI12544)
LS Mean Change
LS Meanfrom baseline
Difference vs. placebo
L (%)(95% CI)
0.43 (25.9)
0.26(0.11, 0.40)
0.39 (25.8)
0.21(0.06, 0.36)
0.18 (10.2)
0.43 (29.0)
0.21(0.13, 0.29)
0.21 (15.6)
0.47 (32.5)
0.24(0.16, 0.32)
0.22 (14.4)

LS Mean Difference in Change from Baseline vs Placebo to Week 12 in PreBronchodilator FEV1 across Baseline Blood Eosinophil Counts (cells/mcL) in
Subjects with Moderate-to-Severe Asthma (QUEST)

Page 41 of 57

Figure 8:

LS Mean Difference in Change from Baseline vs Placebo to Week 12 in Prebronchodilator FEV1 across Baseline FeNO (ppb) in Subjects with Moderateto-Severe Asthma (QUEST)

Figure 9:

Mean Change from Baseline in Pre-Bronchodilator FEV1 (L) Over Time in
Subjects with Moderate-to-Severe Asthma with Baseline Blood Eosinophils≥300 cells/mcL (QUEST)

Additional Secondary Endpoints
ACQ-5 and AQLQ(S) were assessed in QUEST at 52 weeks. The responder rate was defined as
an improvement in score of 0.5 or more (scale range 0-6 for ACQ-5 and 1-7 for AQLQ(S)).
The ACQ-5 responder rate for DUPIXENT 200 mg and 300 mg Q2W in the overall
population was 69% vs 62% placebo (odds ratio 1.37; 95% CI: 1.01, 1.86) and 69% vs
63% placebo (odds ratio 1.28; 95% CI: 0.94, 1.73), respectively; and the AQLQ(S)responder rates were 62% vs 54% placebo (odds ratio 1.61; 95% CI: 1.17, 2.21) and 62%
vs 57% placebo (odds ratio 1.33; 95% CI: 0.98, 1.81), respectively.



The ACQ-5 responder rate for DUPIXENT 200 mg and 300 mg Q2W in subjects withbaseline blood eosinophils ≥300 cells/mcL was 75% vs 67% placebo (odds ratio: 1.46;
Page 42 of 57

95% CI: 0.90, 2.35) and 71% vs 64% placebo (odds ratio: 1.39; 95% CI: 0.88, 2.19),
respectively; and the AQLQ(S) responder rates were 71% vs 55% placebo (odds ratio:
2.02; 95% CI: 1.24, 3.32) and 65% vs 55% placebo (odds ratio: 1.79; 95% CI: 1.13,
2.85), respectively.
Oral Corticosteroid Reduction (VENTURE)
VENTURE evaluated the effect of DUPIXENT on reducing the use of maintenance oralcorticosteroids. The baseline mean oral corticosteroid dose was 12 mg in the placebo group and
11 mg in the group receiving DUPIXENT. The primary endpoint was the percent reduction frombaseline of the final oral corticosteroid dose at Week 24 while maintaining asthma control.
Compared with placebo, subjects receiving DUPIXENT achieved greater reductions in daily
maintenance oral corticosteroid dose, while maintaining asthma control. The mean percent
reduction in daily OCS dose from baseline was 70% (median 100%) in subjects receiving
DUPIXENT (95% CI: 60%, 80%) compared to 42% (median 50%) in subjects receiving placebo(95% CI: 33%, 51%). Reductions of 50% or higher in the OCS dose were observed in 82 (80%)
subjects receiving DUPIXENT compared to 57 (53%) in those receiving placebo. The proportionof subjects with a mean final dose less than 5 mg at Week 24 was 72% for DUPIXENT and 37%
for placebo (odds ratio 4.48 95% CI: 2.39, 8.39). A total of 54 (52%) subjects receiving
DUPIXENT versus 31 (29%) subjects in the placebo group had a 100% reduction in their OCS
dose.
In this 24-week trial, asthma exacerbations (defined as a temporary increase in oral corticosteroid
dose for at least 3 days) were lower in subjects receiving DUPIXENT compared with thosereceiving placebo (annualized rate 0.65 and 1.60 for the DUPIXENT and placebo group,
respectively; rate ratio 0.41 [95% CI 0.26, 0.63]) and improvement in pre-bronchodilator FEV1from baseline to Week 24 was greater in subjects receiving DUPIXENT compared with thosereceiving placebo (LS mean difference for DUPIXENT versus placebo of 0.22 L [95% CI: 0.09
to 0.34 L]). Effects on lung function and on oral steroid and exacerbation reduction were similarirrespective of baseline blood eosinophil levels. The ACQ-5 and AQLQ(S) were also assessed in
VENTURE and showed improvements similar to those in QUEST.
Pediatric Subjects 6 to 11 Years of Age with Asthma
The efficacy and safety of DUPIXENT in pediatric subjects was evaluated in a 52-week
multicenter, randomized, double-blind, placebo-controlled study (VOYAGE; NCT02948959) in
408 subjects 6 to 11 years of age, with moderate-to-severe asthma on a medium or high-dose ICS
and a second controller medication or high-dose ICS alone. Subjects were required to have ahistory of 1 or more asthma exacerbation(s) that required treatment with systemic corticosteroids
or emergency department visit or hospitalization for the treatment of asthma in the year prior totrial entry. Subjects were randomized to DUPIXENT (N=273) or matching placebo (N=135)
every other week based on body weight <30 kg (100 mg Q2W) or ≥30 kg (200 mg Q2W). The
effectiveness of DUPIXENT 300 mg Q4W was extrapolated from efficacy of 100 mg Q2W in
VOYAGE with support from population pharmacokinetic analyses showing higher drug
exposure levels with 300 mg Q4W [see Pediatric Use (8.4) and Pharmacokinetics (12.3)].
The primary endpoint was the annualized rate of severe asthma exacerbation events during the
52-week placebo-controlled period. Severe asthma exacerbations were defined as deteriorationof asthma requiring the use of systemic corticosteroids for at least 3 days or hospitalization orPage 43 of 57

emergency room visit due to asthma that required systemic corticosteroids. The key secondary
endpoint was the change from baseline in pre-bronchodilator FEV1 percent predicted at Week 12.
Additional secondary endpoints included mean change from baseline and responder rates in the
ACQ-7-IA (Asthma Control Questionnaire-7-Interviewer Administered) and PAQLQ(S)-IA(Pediatric Asthma Quality of Life Questionnaire with Standardized Activities Interviewer
Administered) scores.
The demographics and baseline characteristics for VOYAGE are provided in Table 20 below.
Table 20:

Demographics and Baseline Characteristics for VOYAGEParameter

VOYAGE(N=408)Mean age (years) (SD)9 (2)% Female36% White88
Mean body weight (kg)36
Mean exacerbations in previous year (± SD)
2.4 (2.2)
High dose ICS use (%)
44
Pre-dose FEV1 (L) at baseline (± SD)
1.48 (0.41)
Mean percent predicted FEV1 (%) (±SD)
78 (15)
Mean % Reversibility (± SD)
20 (21)
Atopic Medical History % Overall
92(AD %, AR %)(36, 82)
Mean FeNO ppb (± SD)
28 (24)% subjects with FeNO ppb ≥20
50
Median total IgE IU/mL (±SD)
792 (1093)
Mean baseline Eosinophil count (± SD) cells/mcL
502 (395)
ICS = inhaled corticosteroid; FEV1 = Forced expiratory volume in 1 second; AD = atopic dermatitis; AR = allergic
rhinitis; FeNO = fraction of exhaled nitric oxide

DUPIXENT significantly reduced the annualized rate of severe asthma exacerbation events
during the 52-week treatment period compared to placebo in populations with an eosinophilic
phenotype as indicated by elevated blood eosinophils and/or the population with elevated FeNO.
Subgroup analyses for results of DUPIXENT treatment based upon either baseline eosinophil
level or baseline FeNO level were similar to the pediatric (12 to 17 years of age) and adult trials
and are described for the adult and pediatric (12 to 17 years of age) asthma population above. In
subjects with baseline blood eosinophil count <150 cells/mcL and FeNO <20 ppb, similar severe
asthma exacerbation rates were observed between DUPIXENT and placebo.
Significant improvements in percent predicted pre-bronchodilator FEV1 were observed at Week
12. Significant improvements in percent predicted FEV1 were observed as early as Week 2 andwere maintained through Week 52 in VOYAGE (Figure 10).
The efficacy results for VOYAGE are presented in Table 21.

Page 44 of 57

Table 21:

Efficacy Results of DUPIXENT in VOYAGETreatment
Annualized Severe Exacerbations Rate over 52 Weeks
N
DUPIXENT
100 mg Q2Wb (<30 kg)/
200 mg Q2W (≥30 kg)
Placebo

175

EOS ≥300 cells/mcLa
Rate(95% CI)
0.24(0.16, 0.35)

0.67(0.47, 0.95)
Mean Change from Baseline in Percent Predicted FEV1 at Week 12
N
LS mean Δ from Baseline

Rate Ratio(95% CI)
0.35(0.22, 0.56)84

LS meandifference vs. Placebo(95% CI)
5.32(1.76, 8.88)

DUPIXENT
168
10.15
100 mg Q2Wb (<30 kg)/
200 mg Q2W (≥30 kg)
Placebo80
4.83
aThis reflects the prespecified primary analysis population for VOYAGE in the United States.
b
The effectiveness of DUPIXENT 300 mg Q4W was extrapolated from efficacy of 100 mg Q2W.

Figure 10:

Mean Change from Baseline in Percent Predicted Pre-bronchodilator FEV1
(L) Over Time in Pediatric Subjects 6 to 11 Years of Age in VOYAGE(Baseline Blood Eosinophils ≥300 cells/mcL)

Improvements were also observed for ACQ-7-IA and PAQLQ(S)-IA at Week 24 and were
sustained at Week 52. Greater responder rates were observed for ACQ-7-IA and PAQLQ(S)-IA
compared to placebo at Week 24. The responder rate was defined as an improvement in score of
0.5 or more (scale range 0-6 for ACQ-7-IA and 1-7 for PAQLQ(S)-IA). In the subgroup of
subjects with baseline blood eosinophil count ≥300 cells/mcL, DUPIXENT led to a higher
proportion of subjects with a response in ACQ-7-IA (80.6% versus 64.3% for placebo) with an

Page 45 of 57

OR of 2.79 (95% CI: 1.43, 5.44), and in PAQLQ(S)-IA (72.8% versus 63.0% for placebo) withan OR of 1.84 (95% CI: 0.92, 3.65) at Week 24.

14.3

Chronic Rhinosinusitis with Nasal Polyps

The efficacy of DUPIXENT as an add-on maintenance treatment in adults with inadequately
controlled chronic rhinosinusitis with nasal polyps (CRSwNP) was evaluated in two randomized,
double-blind, parallel-group, multicenter, placebo-controlled studies (SINUS-24(NCT02912468) and SINUS-52 (NCT02898454)) in 724 adult subjects 18 years of age and older
on background intranasal corticosteroids (INCS). These studies included subjects with CRSwNP
despite prior sino-nasal surgery or treatment with, or who were ineligible to receive or wereintolerant to, systemic corticosteroids in the past 2 years. Subjects with chronic rhinosinusitis
without nasal polyps were not included in these trials. Rescue with systemic corticosteroids orsurgery was allowed during the studies at the investigator’s discretion. In SINUS-24, a total of
276 subjects were randomized to receive either 300 mg DUPIXENT (N=143) or placebo(N=133) every other week for 24 weeks. In SINUS-52, 448 subjects were randomized to receive
either 300 mg DUPIXENT (N=150) every other week for 52 weeks, 300 mg DUPIXENT(N=145) every other week until Week 24 followed by 300 mg DUPIXENT every 4 weeks until
Week 52, or placebo (N=153). All subjects had evidence of sinus opacification on the Lund
Mackay (LMK) sinus CT scan and 73% to 90% of subjects had opacification of all sinuses.
Subjects were stratified based on their histories of prior surgery and co-morbid
asthma/nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NSAID-ERD). A
total of 63% of subjects reported previous sinus surgery, with a mean number of 2.0 priorsurgeries, 74% used systemic corticosteroids in the previous 2 years with a mean number of 1.6
systemic corticosteroid courses in the previous 2 years, 59% had co-morbid asthma, and 28%
had NSAID-ERD.
The co-primary efficacy endpoints were change from baseline to Week 24 in bilateralendoscopic nasal polyps score (NPS; 0-8 scale) as graded by central blinded readers, and change
from baseline to Week 24 in nasal congestion/obstruction score averaged over 28 days (NC; 0-3
scale), as determined by subjects using a daily diary. For NPS, polyps on each side of the nose
were graded on a categorical scale (0=no polyps; 1=small polyps in the middle meatus notreaching below the inferior border of the middle turbinate; 2=polyps reaching below the lower
border of the middle turbinate; 3=large polyps reaching the lower border of the inferior turbinate
or polyps medial to the middle turbinate; 4=large polyps causing complete obstruction of theinferior nasal cavity). The total score was the sum of the right and left scores. Nasal congestion
was rated daily by the subjects on a 0 to 3 categorical severity scale (0=no symptoms; 1=mild
symptoms; 2=moderate symptoms; 3=severe symptoms).
In both studies, key secondary end-points at Week 24 included change from baseline in: LMK
sinus CT scan score, daily loss of smell, and 22-item sino-nasal outcome test (SNOT-22). The
LMK sinus CT scan score evaluated the opacification of each sinus using a 0 to 2 scale(0=normal; 1=partial opacification; 2=total opacification) deriving a maximum score of 12 perside and a total maximum score of 24 (higher scores indicate more opacification). Loss of smell
was scored reflectively by the subject every morning on a 0-3 scale (0=no symptoms, 1=mild
symptoms, 2=moderate symptoms, 3=severe symptoms). SNOT-22 includes 22 items assessing
symptoms and symptom impact associated with CRSwNP with each item scored from 0 (noPage 46 of 57

problem) to 5 (problem as bad as it can be) with a global score ranging from 0 to 110. SNOT-22
had a 2 week recall period. In the pooled efficacy results, the reduction in the proportion ofsubjects rescued with systemic corticosteroids and/or sino-nasal surgery (up to Week 52) were
evaluated.
The demographics and baseline characteristics of these 2 trials are provided in Table 22 below.
Table 22:

Demographics and Baseline Characteristics of CRSwNP Trials

Parameter

SINUS-24(N=276)50 (13)57
11 (9)
72
65

SINUS-52(N=448)52 (12)62
11 (10)5880Mean age (years) (SD)% MaleMean CRSwNP duration (years) (SD)
Subjects with ≥1 prior surgery (%)
Subjects with systemic corticosteroid use in the previous 2 years(%)
Mean Bilateral endoscopic NPSa (SD), range 0-8
5.8 (1.3)
6.1 (1.2)
Mean Nasal congestion (NC) scorea (SD), range 0-3
2.4 (0.6)
2.4 (0.6)
Mean LMK sinus CT total scorea (SD), range 0-24
19 (4.4)
18 (3.8)
Mean loss of smell scorea (AM), (SD) range 0-3
2.7 (0.5)
2.8 (0.5)
Mean SNOT-22 total scorea (SD), range 0-110
49.4 (20.2)
51.9 (20.9)
Mean blood eosinophils (cells/mcL) (SD)440 (330)
430 (350)
Mean total IgE IU/mL (SD)212 (276)
240 (342)
Atopic Medical History% Overall
75
82
Asthma (%)
58
60
NSAID-ERD (%)
30
27
aHigher scores indicate greater disease severity
SD = standard deviation; AM = morning; NPS = nasal polyps score; SNOT-22 = 22-item sino-nasal outcome test;
NSAID-ERD = asthma/nonsteroidal anti-inflammatory drug exacerbated respiratory disease

Clinical Response (SINUS-24 and SINUS-52)
The results for primary endpoints in CRSwNP studies are presented in Table 23.
Table 23:

Results of the Primary Endpoints in CRSwNP Trials
Placebo(n=133)

SINUS-24
DUPIXENT
300 mg Q2W(n=143)

Primary Endpoints at Week 24
Scores BaselineLS
Baseline
mean
mean
mean
changeLS meandifference vs.
Placebo(95% CI)LS
meanchange

NPS

5.86

0.17

5.64

-1.89

NC

2.45

-0.45

2.26

-1.34

-2.06
(-2.43, -1.69)-0.89(-1.07, -0.71)

Placebo(n=153)

SINUS-52
DUPIXENT
300 mg Q2W(n=295)Baseline
mean

LS
mean
changeBaseline
mean

LS
mean
change

5.96

0.10

6.18

-1.71

2.38

-0.38

2.46

-1.25

A reduction in score indicates improvement.
NPS = nasal polyps score; NC = nasal congestion/obstruction

Statistically significant efficacy was observed in SINUS-52 with regard to improvement inbilateral endoscopic NPS score at week 24 and week 52 (see Figure 11).
Page 47 of 57

LS meandifference vs.
Placebo(95% CI)-1.80(-2.10, -1.51)-0.87(-1.03, -0.71)

Figure 11:

LS Mean Change from Baseline in Bilateral Nasal Polyps Score (NPS) up to
Week 52 in Subjects 18 Years of Age and Older with CRSwNP (SINUS-52 ITT Population)

Similar results were seen in SINUS-24 at Week 24. In the post-treatment period when subjects
were off DUPIXENT, the treatment effect diminished over time (see Figure 12).
Figure 12:

LS Mean Change from Baseline in Bilateral Nasal Polyps Score (NPS) up to
Week 48 in Subjects 18 Years of Age and Older with CRSwNP (SINUS-24 ITT Population)

At Week 52, the LS mean difference for nasal congestion in the DUPIXENT group versus
placebo was -0.98 (95% CI -1.17, -0.79). In both studies, significant improvements in nasal
Page 48 of 57

congestion were observed as early as the first assessment at Week 4. The LS mean difference fornasal congestion at Week 4 in the DUPIXENT group versus placebo was -0.41 (95% CI: -0.52,-0.30) in SINUS-24 and -0.37 (95% CI: -0.46, -0.27) in SINUS-52.
A significant decrease in the LMK sinus CT scan score was observed. The LS mean difference
for LMK sinus CT scan score at Week 24 in the DUPIXENT group versus placebo was -7.44(95% CI: -8.35, -6.53) in SINUS-24 and -5.13 (95% CI: -5.80, -4.46) in SINUS-52. At Week 52,
in SINUS-52 the LS mean difference for LMK sinus CT scan score in the DUPIXENT groupversus placebo was -6.94 (95% CI: -7.87, -6.01).
Dupilumab significantly improved the loss of smell compared to placebo. The LS meandifference for loss of smell at Week 24 in the DUPIXENT group versus placebo was -1.12 (95%
CI: -1.31, -0.93) in SINUS-24 and -0.98 (95% CI: -1.15, -0.81) in SINUS-52. At Week 52, theLS mean difference for loss of smell in the DUPIXENT group versus placebo was -1.10 (95% CI-1.31, -0.89). In both studies, significant improvements in daily loss of smell severity wereobserved as early as the first assessment at Week 4.
Dupilumab significantly decreased sino-nasal symptoms as measured by SNOT-22 compared toplacebo. The LS mean difference for SNOT-22 at Week 24 in the DUPIXENT group versus
placebo was -21.12 (95% CI: -25.17, -17.06) in SINUS-24 and -17.36 (95% CI: -20.87, -13.85)
in SINUS-52. At Week 52, the LS mean difference in the DUPIXENT group versus placebo
was -20.96 (95% CI -25.03, -16.89).
In the pre-specified multiplicity-adjusted pooled analysis of two studies, treatment with
DUPIXENT resulted in significant reduction of systemic corticosteroid use and need forsino-nasal surgery versus placebo (HR of 0.24; 95% CI: 0.17, 0.35) (see Figure 13). The
proportion of subjects who required systemic corticosteroids was reduced by 74% (HR of 0.26;
95% CI: 0.18, 0.38). The total number of systemic corticosteroid courses per year was reducedby 75% (RR of 0.25; 95% CI: 0.17, 0.37). The proportion of subjects who required surgery was
reduced by 83% (HR of 0.17; 95% CI: 0.07, 0.46).

Page 49 of 57

Figure 13:

Kaplan Meier Curve for Time to First Systemic Corticosteroid Use and/or
Sino-Nasal Surgery During Treatment Period in Subjects 18 Years of Ageand Older with CRSwNP (SINUS-24 and SINUS-52 Pooled - ITT
Population)

The effects of DUPIXENT on the primary endpoints of NPS and nasal congestion and the key
secondary endpoint of LMK sinus CT scan score were consistent in subjects with prior surgery
and without prior surgery.
In subjects with co-morbid asthma, improvements in pre-bronchodilator FEV1 were similar to
subjects in the asthma program.

14.4

Eosinophilic Esophagitis

Adult and Pediatric Subjects 12 Years of Age and Older with EoE
A single randomized, double-blind, parallel-group, multicenter, placebo-controlled trial,
including two 24-week treatment periods (Study EoE-1 Parts A and B) was conducted in adultand pediatric subjects 12 years of age and older, weighing at least 40 kg, with EoE(NCT03633617). In both parts, subjects were randomized to receive 300 mg DUPIXENT every
week or placebo. Eligible subjects had ≥15 intraepithelial eosinophils per high-power field(eos/hpf) following a treatment course of a proton pump inhibitor (PPI) either prior to or during
the screening period and symptoms of dysphagia as measured by the Dysphagia Symptom
Questionnaire (DSQ). At baseline, 43% of subjects in Part A and 37% of subjects in Part B had ahistory of prior esophageal dilations.
Demographics and baseline characteristics were similar in Parts A and B. A total of 81 subjects(61 adults and 20 pediatric subjects) were enrolled in Part A and 159 subjects (107 adults and 52
pediatric subjects) were enrolled in Part B. The mean age in years was 32 years (range 13 to 62
Page 50 of 57

years) in Part A and 28 years (range 12 to 66 years) in Part B. The majority of subjects weremale (60% in Part A and 68% in Part B) and White (96% in Part A and 90% in Part B). The
mean baseline DSQ score (SD) was 33.6 (12.4) in Part A and 37.2 (10.7) in Part B.
The coprimary efficacy endpoints in Parts A and B were the (1) proportion of subjects achieving
histological remission defined as peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf
at Week 24; and (2) the absolute change in the subject-reported DSQ score from baseline to
Week 24.
Efficacy results for Parts A and B are presented in Table 24.
Table 24:

Efficacy Results of DUPIXENT at Week 24 in Adult and Pediatric Subjects
12 Years of Age and Older with EoE (Study EoE-1 Parts A and B)
Study EoE-1 Part A
DUPIXENT
Placebob
Differenceb
300 mg QW
vs. Placebo(95% CI)b
N = 42
N = 39Study EoE-1 Part B
DUPIXENT
Placebob
Differenceb
300 mg QW
vs. Placebo(95% CI)b
N = 80N = 79Co-primary Endpoints
Proportion of subjects
achieving histological
25
2
57.0
47
5
53.5
remission (peak esophageal(59.5)(5.1)(40.9, 73.1)(58.8)(6.3)(41.2, 65.8)
intraepithelial eosinophil count≤6 eos/hpf), n (%)
Absolute change from baseline
-21.9
-9.6
-12.3
-23.8
-13.9
-9.9
in DSQ score (0-84a), LS mean
(2.5)
(2.8)
(-19.1, -5.5)
(1.9)
(1.9)
(-14.8, -5.0)(SE)aTotal biweekly DSQ scores range from 0 to 84; higher scores indicate greater frequency and severity of dysphagiab
For histological remission, the difference in percentages is estimated using the Cochran Mantel Haenszel method,
adjusting for randomization stratification factors. For absolute change in DSQ score, the LS mean changes, standard
errors, and differences are estimated using an ANCOVA model with treatment group, randomization stratification factors,
and baseline measurement as covariates.

In Parts A and B, a greater proportion of subjects randomized to DUPIXENT achieved
histological remission (peak esophageal intraepithelial eosinophil count ≤6 eos/hpf) compared toplacebo. Treatment with DUPIXENT also resulted in a significant improvement in LS meanchange in DSQ score compared to placebo at Week 24. The results of the anchor-based analyses
that incorporated the subjects’ perspectives indicated that the observed improvement indysphagia from Parts A and B is representative of a clinically meaningful within-subject
improvement.
Pediatric Subjects 1 to 11 Years of Age, Weighing at Least 15 kg, with EoE
The efficacy and safety of DUPIXENT was evaluated in pediatric subjects 1 to 11 years of age,weighing at least 15 kg, with EoE in a randomized, blinded, parallel-group, multicenter trial(Study EoE-2 Parts A and B; NCT04394351). Eligible subjects had ≥15 intraepithelial
eosinophils per high-power field (eos/hpf) despite a treatment course of a proton pump inhibitor(PPI) either prior to or during the screening period and a history of EoE signs and symptoms.
Part A evaluated weight-based dosing regimens of DUPIXENT, 200 mg Q2W (≥15 to <30 kg)
and 300 mg Q2W (≥30 to <60 kg), or placebo in 61 subjects during the 16-week treatment
period.

Page 51 of 57

The recommended dosage of 300 mg QW for pediatric subjects 1 to 11 years of age weighing≥40 kg is based on modeled pharmacokinetic data to provide comparable exposures to the 300
mg QW dosage in adult and pediatric subjects 12 years of age and older weighing ≥40 kg with
EoE [see Dosage and Administration (2.6) and Pharmacokinetics (12.3)].
Forty-seven subjects who completed Part A were evaluated in the 36-week extended active
treatment period (Study EoE-2 Part B). All subjects in Part B were treated with the weight-based
dosing regimens of DUPIXENT described for Part A.
Of the total subjects evaluated in Part A, the mean age was 8 years, the median weight was 28kg, and 75% were male. Seven percent identified as Hispanic or Latino; 85% identified as White,
12% as Black, 2% as Asian, and 2% identified as another racial subgroup.
The primary efficacy endpoint in Part A was the proportion of subjects achieving histologicalremission defined as peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf at Week 16.
Efficacy results for Part A are presented in Table 25.
Table 25:

Efficacy Results of DUPIXENT at Week 16 in Subjects 1 to 11 Years of Agewith EoE, Weighing at Least 15 kg (Study EoE-2 Part A)
DUPIXENTa
N=32

Placebo
N=29

Difference vs Placebo(95% CI)

Proportion of subjects achieving
histological remission (peak
21
1
62.0
esophageal intraepithelial(65.6)(3.4)(44.00, 79.95)
eosinophil count ≤6 eos/hpf), n(%)ba
DUPIXENT was evaluated at tiered dosing regimens based on body weight: ≥15 to <30 kg (200 mg Q2W) and ≥30 to<60 kg (300 mg Q2W). The 300 mg Q2W dosing regimen is lower than the recommended dosage of DUPIXENT insubjects ≥40 kg [see Dosage and Administration (2.6)].
b
The difference in percentages is estimated using the Mantel-Haenszel method, adjusting for baseline weight group (≥15 to<30 kg and ≥30 to <60 kg).

In Part B, histological remission was achieved at Week 52 in 17/32 subjects treated with
DUPIXENT in Parts A and B and 8/15 subjects treated with placebo in Part A and DUPIXENTin Part B.
In Study EoE-2 Part A, an observer-reported outcome, the Pediatric EoE Sign/Symptom
Questionnaire-Caregiver (PESQ-C), was used to measure signs of EoE. A greater decrease in the
proportion of days with 1 or more signs of EoE (based on the PESQ-C) was observed for
subjects treated with DUPIXENT compared to placebo after 16 weeks of treatment.

14.5

Prurigo Nodularis

The prurigo nodularis (PN) development program included two 24-week randomized, doubleblind, placebo-controlled, multicenter, parallel-group trials (PRIME (NCT04183335) and
PRIME 2 (NCT04202679)) in 311 adult subjects 18 years of age and older with pruritus (WINRS ≥ 7 on a scale of 0 to 10) and greater than or equal to 20 nodular lesions. PRIME and
PRIME 2 assessed the effect of DUPIXENT on pruritus improvement as well as its effect on PN
lesions.

Page 52 of 57

In these two trials, subjects received either subcutaneous DUPIXENT 600 mg (two 300 mg
injections) on day 1, followed by 300 mg once every other week (Q2W) for 24 weeks, ormatching placebo.
In these trials, the mean age was 49.5 years, the median weight was 71 kg, 65% of subjects werefemale, 57% were White, 6% were Black, and 34% were Asian. At baseline, the mean Worst
Itch-Numeric Rating Scale (WI-NRS) was 8.5, 66% had 20 to 100 nodules (moderate), and 34%
had greater than 100 nodules (severe). Eleven percent (11%) of subjects were taking stable dosesof antidepressants at baseline and were instructed to continue taking these medications during thetrial. Forty-three percent (43%) had a history of atopy (defined as having a medical history ofAD, allergic rhinitis/rhinoconjunctivitis, asthma, or food allergy).
The WI-NRS is comprised of a single item, rated on a scale from 0 (“no itch”) to 10 (“worst
imaginable itch”). Subjects were asked to rate the intensity of their worst pruritus (itch) over the
past 24 hours using this scale. The Investigator’s Global Assessment for Prurigo Nodularis-Stage(IGA PN-S) is a scale that measures the approximate number of nodules using a 5-point scalefrom 0 (clear) to 4 (severe).
Efficacy was assessed with the proportion of subjects with improvement (reduction) in WI-NRS
by ≥4 points, the proportion of subjects with IGA PN-S 0 or 1 (the equivalent of 0-5 nodules),and the proportion of subjects who achieved a response in both WI-NRS and IGA PN-S per thecriteria described above.
The efficacy results for PRIME and PRIME2 are presented in Table 26 and Figures 14, 15, and16.
Table 26:

Efficacy Results of DUPIXENT in PRIME and PRIME2
Placebo(N=76)

Proportion of subjects with both an
improvement (reduction) in WINRS by ≥4 points from baseline to
Week 24 and an IGA PN-S 0 or 1 at
Week 24b
Proportion of subjects withimprovement (reduction) in WINRS by ≥4 points from baseline at
Week 24b
Proportion of subjects with IGA
PN-S 0 or 1 at Week 24b

9.2%

PRIME
DUPIXENT Difference
300 mg Q2W (95% CI) for
DUPIXENT vs.
(N=75)
Placebo

38.7%

18.4%

60.0%

18.4%

48.0%

29.6%
(16.4, 42.8)

42.7%(27.8, 57.7)
28.3%(13.4, 43.2)

Placebo(N=82)

8.5%

PRIME2
DUPIXENT
Difference
300 mg Q2W (95% CI) for
DUPIXENT vs.
(N=78)
Placebo

32.1%

19.5%

57.7%

15.9%

44.9%

Proportion of subjects with
29.2%
improvement (reduction) in WI15.8%a
44.0%a22.0%
37.2%
NRS by ≥4 points from baseline at(14.5, 43.8)aWeek 12ba
Not adjusted for multiplicity in PRIME.
b
Subjects who received rescue treatment earlier or had missing data were considered as non-responders.

Page 53 of 57

25.5%(13.1, 37.9)

42.6%(29.1, 56.1)
30.8%(16.4, 45.2)
16.8%(2.3, 31.2)

Figure 14:

Proportion of Adult Subjects with PN with Both WI-NRS ≥4-point
Improvement and IGA PN-S 0 or 1 Over Time in PRIME and PRIME2

Figure 15:

Proportion of Adult Subjects with PN with WI-NRS ≥4-point Improvement
Over Time in PRIME and PRIME2

Page 54 of 57

Figure 16:

Proportion of Adult Subjects with IGA PN-S 0 or 1 Over Time in PRIME
and PRIME 2

The efficacy data did not show differential treatment effect across demographic subgroups.

16

HOW SUPPLIED/STORAGE AND HANDLINGHow Supplied
DUPIXENT (dupilumab) Injection is a clear to slightly opalescent, colorless to pale yellow
solution, supplied in single-dose pre-filled syringes with needle shield or pre-filled pens.
The pre-filled syringe with needle shield is designed to deliver:

300 mg of DUPIXENT in 2 mL solution (NDC 0024-5914-00)



200 mg of DUPIXENT in 1.14 mL solution (NDC 0024-5918-00)

The pre-filled pen is designed to deliver:

300 mg of DUPIXENT in 2 mL solution (NDC 0024-5915-00)



200 mg of DUPIXENT in 1.14 mL solution (NDC 0024-5919-00)

DUPIXENT is available in cartons containing 2 pre-filled syringes with needle shield or 2 prefilled pens.
Pack Size

300 mg/2 mL Pre-filled Syringe with
Needle Shield

200 mg/1.14 mL Pre-filled Syringe with
Needle Shield

Pack of 2 syringes

NDC 0024-5914-01

NDC 0024-5918-01

Pack Size
Pack of 2 pens

300 mg/2 mL Pre-filled Pen
NDC 0024-5915-02

200 mg/1.14 mL Pre-filled Pen
NDC 0024-5919-02

Page 55 of 57

Storage and Handling
DUPIXENT is sterile and preservative-free. Discard any unused portion.
Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.
If necessary, DUPIXENT may be kept at room temperature up to 25°C (77°F) for a maximum of
14 days. Do not store above 25°C (77°F). After removal from the refrigerator, DUPIXENT must
be used within 14 days or discarded.
Do not expose DUPIXENT to heat or direct sunlight.
Do NOT freeze. Do NOT shake.

17

PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information andInstructions for Use).
Pregnancy Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to
DUPIXENT during pregnancy. Encourage participation and advise patients about how they may
enroll in the registry [see Use in Specific Populations (8.1)].
Administration Instructions
Provide proper training to patients and/or caregivers on proper subcutaneous injection technique,including aseptic technique, and the preparation and administration of DUPIXENT prior to use.
Advise patients to follow sharps disposal recommendations [see Dosage and Administration(2.1) and Instructions for Use].
Hypersensitivity
Advise patients to discontinue DUPIXENT and to seek immediate medical attention if theyexperience any symptoms of systemic hypersensitivity reactions [see Warnings and Precautions(5.1)].
Conjunctivitis and Keratitis
Advise patients to consult their healthcare provider if new onset or worsening eye symptoms
develop [see Warnings and Precautions (5.2)].
Eosinophilic Conditions
Advise patients to notify their healthcare provider if they present with clinical features of
eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis withpolyangiitis [see Warnings and Precautions (5.3)].
Not for Acute Asthma Symptoms or Deteriorating Disease
Inform patients that DUPIXENT does not treat acute asthma symptoms or acute exacerbations.
Inform patients to seek medical advice if their asthma remains uncontrolled or worsens after
initiation of treatment with DUPIXENT [see Warnings and Precautions (5.4)].

Page 56 of 57

Reduction in Corticosteroid Dosage
Inform patients to not discontinue systemic or inhaled corticosteroids except under the directsupervision of a healthcare provider. Inform patients that reduction in corticosteroid dose may be
associated with systemic withdrawal symptoms and/or unmask conditions previously suppressedby systemic corticosteroid therapy [see Warnings and Precautions (5.5)].
Patients with Co-morbid Asthma
Advise patients with co-morbid asthma not to adjust or stop their asthma treatment without
talking to their healthcare providers [see Warnings and Precautions (5.6)].
Arthralgia
Advise patients to report new onset or worsening joint symptoms to their healthcare provider[see Warnings and Precautions (5.7)].
Parasitic (Helminth) Infections
Advise patients to notify their healthcare provider if they present with clinical features consistent
with helminthic infection [see Warnings and Precautions (5.8)].
Vaccinations
Advise patients that vaccination with live vaccines is not recommended immediately prior to andwhile they are receiving DUPIXENT. Instruct patients to inform their healthcare provider thatthey are taking DUPIXENT prior to a potential vaccination [see Warnings and Precautions(5.9)].
Manufactured by:Regeneron Pharmaceuticals, Inc.
Tarrytown, NY 10591
U.S. License No. 1760
Marketed by:sanofi-aventis U.S. LLC (Bridgewater, NJ 08807) andRegeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591)
For patent information: www.dupixent-patents.com
DUPIXENT® is a registered trademark of Sanofi Biotechnology© 2024 Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC. All rights reserved.

Page 57 of 57

Patient Information
DUPIXENT® (DU-pix-ent)(dupilumab)
injection, for subcutaneous use
What is DUPIXENT?
DUPIXENT is a prescription medicine used:o to treat adults and children 6 months of age and older with moderate-to-severe eczema (atopic dermatitis or AD) that is
not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT
can be used with or without topical corticosteroids.
o with other asthma medicines for the maintenance treatment of moderate-to-severe asthma in adults and children 6 yearsof age and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe
asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oralcorticosteroids you need while preventing severe asthma attacks and improving your breathing.
DUPIXENT is not used to treat sudden breathing problems.
o with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adults andchildren 12 years of age and older whose disease is not controlled.
o to treat adults and children 1 year of age and older with eosinophilic esophagitis (EoE), who weigh at least 33 pounds(15 kg).
o to treat adults with prurigo nodularis (PN).
 DUPIXENT works by blocking two proteins that contribute to a type of inflammation that plays a major role in atopic dermatitis,
asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and prurigo nodularis.
 It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 months of age.
 It is not known if DUPIXENT is safe and effective in children with asthma under 6 years of age.
 It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyps under 12 years ofage.
 It is not known if DUPIXENT is safe and effective in children with eosinophilic esophagitis under 1 year of age, or who weighless than 33 pounds (15 kg).
 It is not known if DUPIXENT is safe and effective in children with prurigo nodularis under 18 years of age.
Do not use DUPIXENT if you are allergic to dupilumab or to any of the ingredients in DUPIXENT. See the end of this Patient
Information leaflet for a complete list of ingredients in DUPIXENT.
Before using DUPIXENT, tell your healthcare provider about all your medical conditions, including if you: have eye problems.
 have a parasitic (helminth) infection.
 are scheduled to receive any vaccinations. You should not receive a “live vaccine” right before and during treatment with
DUPIXENT.
 are pregnant or plan to become pregnant. It is not known whether DUPIXENT will harm your unborn baby.
Pregnancy Exposure Registry. There is a pregnancy exposure registry for women who use DUPIXENT during pregnancy.
The purpose of this registry is to collect information about the health of you and your baby. Your healthcare provider can enroll
you in this registry. You may also enroll yourself or get more information about the registry by calling 1-877-311-8972 or goingto https://mothertobaby.org/ongoing-study/dupixent/.
 are breastfeeding or plan to breastfeed. It is not known whether DUPIXENT passes into your breast milk.
Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins,
and herbal supplements.
Especially tell your healthcare provider if you:
 are taking oral, topical, or inhaled corticosteroid medicines have asthma and use an asthma medicine
 have atopic dermatitis, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, or prurigo nodularis and also haveasthmaDo not change or stop your corticosteroid medicine or other asthma medicine without talking to your healthcare provider. Thismay cause other symptoms that were controlled by the corticosteroid medicine or other asthma medicine to come back.
How should I use DUPIXENT?
 See the detailed “Instructions for Use” that comes with DUPIXENT for information on how to prepare and inject
DUPIXENT and how to properly store and throw away (dispose of) used DUPIXENT pre-filled syringes and pre-filledpens.
 Use DUPIXENT exactly as prescribed by your healthcare provider.
 Your healthcare provider will tell you how much DUPIXENT to inject and how often to inject it.
 DUPIXENT comes as a single-dose pre-filled syringe with needle shield or as a pre-filled pen.
o The DUPIXENT pre-filled pen is only for use in adults and children 2 years of age and older.
o The DUPIXENT pre-filled syringe is for use in adults and children 6 months of age and older.
 DUPIXENT is given as an injection under the skin (subcutaneous injection).

 If your healthcare provider decides that you or a caregiver can give the injections of DUPIXENT, you or your caregiver should
receive training on the right way to prepare and inject DUPIXENT. Do not try to inject DUPIXENT until you have been shown
the right way by your healthcare provider. In children 12 years of age and older, it is recommended that DUPIXENT be given
by or under the supervision of an adult. In children 6 months to less than 12 years of age, DUPIXENT should be given by acaregiver.
 If your dose schedule is every week and you miss a dose of DUPIXENT: Give the DUPIXENT injection as soon as
possible and start a new every week dose schedule from the time you remember to take your DUPIXENT injection.
 If your dose schedule is every other week and you miss a dose of DUPIXENT: Give the DUPIXENT injection within 7 days
from the missed dose, then continue with your original schedule. If the missed dose is not given within 7 days, wait until thenext scheduled dose to give your DUPIXENT injection.
 If your dose schedule is every 4 weeks and you miss a dose of DUPIXENT: Give the DUPIXENT injection within 7 days
from the missed dose, then continue with your original schedule. If the missed dose is not given within 7 days, start a new
every 4 week dose schedule from the time you remember to take your DUPIXENT injection.
 If you inject too much DUPIXENT, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest
hospital emergency room right away.
 Your healthcare provider may prescribe other medicines to use with DUPIXENT. Use the other prescribed medicines exactly
as your healthcare provider tells you to.
What are the possible side effects of DUPIXENT?
DUPIXENT can cause serious side effects, including: Allergic reactions. DUPIXENT can cause allergic reactions that can sometimes be severe. Stop using DUPIXENT and tell
your healthcare provider or get emergency help right away if you get any of the following signs or symptoms:o breathing problems or wheezingo swelling of the face, lips, mouth,
o fainting, dizziness, feelingo fast pulse
tongue, or throat
lightheadedo fevero hiveso joint paino general ill feelingo itchingo skin rasho swollen lymph nodes
o nausea or vomitingo cramps in your stomach-area
 Eye problems. Tell your healthcare provider if you have any new or worsening eye problems, including eye pain or changes invision, such as blurred vision. Your healthcare provider may send you to an ophthalmologist for an eye exam if needed.
 Inflammation of your blood vessels. Rarely, this can happen in people with asthma who receive DUPIXENT. This may
happen in people who also take a steroid medicine by mouth that is being stopped or the dose is being lowered. It is not known
whether this is caused by DUPIXENT. Tell your healthcare provider right away if you have:o chest paino rasho worsening shortness of breatho a feeling of pins and needles or numbness of your arms or legso persistent fever Joint aches and pain. Joint aches and pain can happen in people who use DUPIXENT. Some people have had trouble walking
or moving due to their joint symptoms, and in some cases needed to be hospitalized. Tell your healthcare provider about any
new or worsening joint symptoms. Your healthcare provider may stop DUPIXENT if you develop joint symptoms.
The most common side effects of DUPIXENT include: injection site reactions
 dizziness upper respiratory tract infections
 muscle pain eye and eyelid inflammation, including redness, swelling, and diarrhea
itching, sometimes with blurred vision pain in the throat (oropharyngeal pain)
 dry eye gastritis
 herpes virus infections
 joint pain (arthralgia)
 common cold symptoms (nasopharyngitis)
 trouble sleeping (insomnia)
 cold sores in your mouth or on your lips
 toothache high count of a certain white blood cell (eosinophilia)
 parasitic (helminth) infections
The following additional side effects have been reported with DUPIXENT: facial rash or redness
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all of the possible side effects of DUPIXENT.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store DUPIXENT?
 Store DUPIXENT in the refrigerator between 36ºF to 46ºF (2ºC to 8ºC).
 Store DUPIXENT in the original carton to protect from light.
 DUPIXENT can be stored at room temperature up to 77°F (25°C) up to 14 days. Throw away (dispose of) any DUPIXENT thathas been left at room temperature for longer than 14 days.
 Do not heat or put DUPIXENT into direct sunlight.
 Do not freeze. Do not shake.
Keep DUPIXENT and all medicines out of the reach of children.

General information about the safe and effective use of DUPIXENT.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use DUPIXENT
for a condition for which it was not prescribed. Do not give DUPIXENT to other people, even if they have the same symptoms thatyou have. It may harm them. You can ask your pharmacist or healthcare provider for information about DUPIXENT that is written
for health professionals.
What are the ingredients in DUPIXENT?
Active ingredient: dupilumab
Inactive ingredients: L-arginine hydrochloride, L-histidine, polysorbate 80, sodium acetate, sucrose, and water for injection.
Manufactured by: Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591 U.S. License No. 1760
Marketed by: sanofi-aventis U.S. LLC (Bridgewater, NJ 08807) and Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591)
DUPIXENT® is a registered trademark of Sanofi Biotechnology / © 2024 Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC. All rights reserved.
For more information about DUPIXENT, go to www.DUPIXENT.com or call 1-844-DUPIXENT (1-844-387-4936).
This Patient Information has been approved by the U.S. Food and Drug Administration.

Revised: September 2024