Nirsevimab for the 

prevention of RSV in 

all infants

October 20, 2022

1

AstraZeneca and Sanofi
2

Topics

Additional data from clinical trials

Duration of protection

Implementation
Term and Preterm Healthy Infants 29+ wGA

Infants Eligible to Receive 

Palivizumab

Similar Study Design Across Complementary Populations

STUDY 

POPULATION

• Infants ≥35 wGA

• Not eligible to receive 

palivizumab (AAP or other 

national/local guidelines)

• Infants 29-<35 wGA

• Not eligible to receive 

palivizumab (AAP or other 

national/local guidelines)

• Preterm Infants <35 wGA

Infants with CLD/CHD

• Eligible to receive palivizumab 

(AAP or other national/local 

guidelines)

COMPARATOR 2:1 Nirsevimab: Placebo 2:1 Nirsevimab: Placebo 2:1 Nirsevimab: Palivizumab 

Efficacy, Safety and PK Safety and PK

(Efficacy via PK)

3

Nirsevimab: A Development Program Conducted Across All Infants

PK, pharmacokinetics.

1 Hammitt LL,et al N Engl J Med. 2022 Mar 3;386(9):837-846. 2. Griffin MP, et al. N Engl J Med. 2020 Jul 30;383(5):415-425. 3. Domachowske Joseph et al. N Engl J 

Med 2022 Mar 386:9, 892-894. 

PHASE 3 Pivotal1

(N ~ 3000)

PHASE 2b POC/Pivotal2

(N ~ 1500)

PHASE 2/3 Pivotal3

(N ~ 1500)
4

Impact of COVID-19 Pandemic on the Phase 3 MELODY Trial

1. Hammitt LL et al. N Engl J Med 2022;386:837-46.

* EMA consultation in parallel

MELODY (Primary) 

Enrollment (N=1490)

FDA consultation 

for MELODY*

MELODY 

Enrollment (N=1522)

MELODY All Subjects Analysis

(N=3012)

Covid-19 

Pandemic 

declared

2019 2020 2021 2022

Study enrollment and location

• Enrollment began 23 July 2019 

• 150 sites (20 countries) in the 

Northern Hemisphere enrolled 1028 

subjects in 2019 and experienced a typical 

RSV season 

• 10 sites (in South Africa) in the 

Southern Hemisphere enrolled 462 subjects 

in early 2020

Situation and mitigation 

• Onset of the COVID-19 pandemic in March 2020 led to several 

operational challenges leading to a pause in enrollment for MELODY

• No RSV cases occurred during the typical 2020 Southern 

Hemisphere

• After consultation with FDA, decision was made to analyze the 

primary endpoint after first 1490 enrolled (Primary).

• Study enrollment resumed in 2021.

MELODY enrollment 

resumed

MELODY Primary

Analysis
FOR DISCUSSION ONLY. DO NOT COPY OR DISTRIBUTE

Term and Preterm Healthy Infants 29+ wGA Infants Eligible to Receive 

Palivizumab

STUDY 

POPULATION

• 1490 Infants ≥35 wGA (Primary 

cohort only)

• Not eligible to receive palivizumab 

(AAP or other national/local guidelines)

• 1453 Infants 29-<35 wGA

• Not eligible to receive palivizumab 

(AAP or other national/local guidelines)

• 615 preterm infants <35 wGA

• 310 infants with CLD/CHD

(196 from both <29 wGA)

COMPARATOR 2:1 Nirsevimab:Placebo 2:1 Nirsevimab:Placebo 2:1 Nirsevimab:Palivizumab

ENDPOINT 

RESULTS

• Primary Endpoint (N=1490):

Incidence of RSV confirmed MA-LRTI 

through 150 days after dosing

• Efficacy: 74.5% (49.6, 87.1)

• Secondary Endpoint (N=1490): 

• Incidence of RSV-LRTI hospitalization 

through 150 days after dosing

• Safety, PK, and ADA

• Efficacy: 62.1% (-8.6, 86.8)

• Primary Endpoint: 

Incidence of RSV confirmed MA-LRTI 

through 150 days after dosing

• Efficacy: 70.1% (52.3, 81.2)

<5kg-50mg: 86.2% (68.1, 94.0)

• Secondary Endpoint: 

Incidence of RSV-LRTI hospitalization 

through 150 days after dosing

• Safety†, PK, and ADA

• Efficacy: 78.4% (51.9, 90.3)

<5kg-50mg: 86.5% (53.5, 96.1)

• Primary Endpoint:

Safety profile of nirsevimab was 

similar to palivizumab

• Nirsevimab Efficacy Extrapolated 

via PK

• Secondary Endpoint: 

Incidence of RSV-LRTI 

hospitalization through 150 days 

after dosing

• Safety†, PK, and ADA

5

Nirsevimab: A Development Program Across All Infants

MA LRTI, medically attended lower respiratory tract infection; PK, pharmacokinetics.

1 Hammitt LL,et al N Engl J Med. 2022 Mar 3;386(9):837-846.. 2. Griffin MP, et al. N Engl J Med. 2020 Jul 30;383(5):415-425. 3. Domachowske Joseph et al. N Engl

J Med 2022 Mar 386:9, 892-894. 5

PHASE 3 Pivotal1 PHASE 2b POC/Pivotal2 PHASE 2/3 Pivotal3
6

• MELODY All Subjects through D151 efficacy and safety

• Pooled MELODY All Subjects AND Phase 2b recommended dose

• Efficacy through D151

• Efficacy by subgroup

• Efficacy by subtype RSV A and RSV B 

• MELODY (primary cohort) 2nd season RSV incidence D361 - D511

Additional Data
MELODY All Subjects
8

MELODY All Subjects – Efficacy through D151

Definition

Placebo

(N=1003)

Nirsevimab

(N=2009) Efficacy

n % n % Efficacy 95% CI

MA RSV LRTI 54 5.4 24 1.2 76.4 62.3-85.2

MA RSV LRTI 

with 

hospitalization

20 2.0 9 0.4 76.8 49.4-89.4

MA RSV LRTI 

(very severe) 17 1.7 7 0.3 78.6 48.8-91.0

LRTI, lower respiratory tract infection; MA, medically attended; RSV, respiratory syncytial virus.

Very severe = hospitalization + requirement for supplemental oxygen and/or intravenous fluids
9

• No SAEs or deaths were considered related to nirsevimab by the investigator

• No anaphylaxis or serious allergic reactions attributable to nirsevimab

MELODY All Subjects – Safety Summary

Safety through D151

Uncommon = frequency ≥ 1/1000 to <1/100
CONFIDENTIAL FOR ACIP RSV WORKING GROUP DISCUSSION ONLY, DO NOT COPY OR DISTRIBUTE

Pooled MELODY All Subjects 

AND 

Phase 2b recommended dose
11

Complementary and Similar Study Designs

Primary endpoint

• Incidence of MA LRTI (inpatient and outpatient) caused by 

RT-PCR confirmed RSV through 150 days

Secondary and exploratory endpoints

• Incidence of hospitalization due to RT-PCR-confirmed RSV 

through 150 days

• Safety (evaluated through one-year post-dose)

• Pharmacokinetics and anti-drug antibodies

• In MELODY, infants were followed for LRTI through 511 

days

Treatment

• Infants were randomized 2:1 to receive a single IM dose of 

nirsevimab or placebo

− MELODY: if <5 kg, 50 mg; if ≥5 kg, 100 mg

− Phase 2b: all infants received 50 mg, regardless of 

weight

MA, medically attended; RT-PCR, reverse-transcriptase polymerase chain reaction. 1. Hammitt et al, N Engl J Med 2022;386:837-46; 2. Griffin et al, N 

Engl J Med 2020;383:415

N ~ 1000

N ~ 500

Monitor for LRTI

endpoint

Monitor for LRTI

Monitor for LRTI

endpoint

Monitor for LRTI

Day 1 31 151 361

Day 1 15 151 361

Nirsevimab group: single IM dose 

<5 kg, 50 mg; ≥5kg, 100 mg 

Placebo group: ingle IM dose of saline

Participant randomization (2:1) and dosing

Post dose follow-up visits Informed consent Screening

N ~ 1000

N ~ 500

Day 1 91 151 361

Day 1 91 151 361

Nirsevimab group: Single 50 mg IM dose

Placebo group: single IM dose of saline

Participant randomization (2:1) and dosing

Post dose follow-up visits Informed consent Screening

Phase 3 MELODY1

Phase 2b2

31 91 511

15 91 511

8 31

8 31

Monitored for RSV 

cases in 2nd season
Pooled MELODY All Subjects AND Phase 2b Recommended Dose 

Definition

Placebo

(N=1293)

Nirsevimab

(N=2579) Efficacy

n % n % Efficacy 95% CI

MA RSV LRTI 80 6.2 31 1.2 79.0 68.5-86.1

MA RSV LRTI 

with 

hospitalization

33 2.6 12 0.5 80.6 62.3-90.1

MA RSV LRTI 

(very severe) 28 2.2 7 0.3 86.2 68.1-94.0

Efficacy through D151 MELODY subjects N=3012

Ph 2b recommended dose subjects N=860

LRTI, lower respiratory tract infection; MA, medically attended; RSV, respiratory syncytial virus.

Very severe = hospitalization + requirement for supplemental oxygen and/or intravenous fluids
13 |

p-value Infants Events Infants Events Placebo Nirsevimab RRR (95% CI)

Interaction Number of O bserved Number of O bserved Favors Favors

Placebo (N = 1293) Nirsevimab (N = 2579)

80.6 (70.8, 87.1)

79.5 (66.8, 87.3)

83.0 (62.8, 92.3)

73.8 (58.1, 83.6)

96.1 (83.5, 99.1)

68.7 (-28.3, 92.3)

72.0 (52.5, 83.5)

88.1 (76.4, 94.0)

78.7 (65.2, 86.9)

85.6 (29.6, 97.1)

82.7 (59.7, 92.6)

77.6 (61.8, 86.9)

84.0 (69.6, 91.6)

79.9 (54.7, 91.1)

76.7 (48.9, 89.3)

82.8 (68.7, 90.5)

76.4 (62.3, 85.2)

-100 -50 0 50 100

31 ( 1.2)

23 ( 1.2)

8 ( 1.2)

26 ( 1.5)

2 ( 0.3)

3 ( 1.6)

21 ( 1.5)

10 ( 0.8)

22 ( 1.5)

2 ( 0.5)

7 ( 1.0)

19 ( 1.4)

12 ( 1.0)

8 ( 1.6)

9 ( 1.1)

14 ( 1.1)

24 ( 1.2)

2579

1890

689

1679

717

183

1369

1210

1447

419

709

1370

1206

505

799

1275

2009

80 ( 6.2)

55 ( 5.9)

25 ( 6.9)

49 ( 5.9)

26 ( 7.1)

5 ( 5.3)

36 ( 5.5)

44 ( 6.9)

53 ( 7.1)

6 ( 3.4)

21 ( 5.7)

42 ( 6.2)

38 ( 6.2)

19 ( 7.9)

19 ( 4.8)

42 ( 6.4)

54 ( 5.4)

1293

929

364

834

365

94

653

640

747

178

368

682

611

241

396

656

1003

N/A

0.6720

0.0031

0.0458

0.8561

0.4288

0.8335

0.3010

O verall

Subgroup

Hemisphere

Age at randomization

Sex

Ancestry

Weight on Day 1

Region

Study Group

Northern Hemisphere

Southern Hemisphere

<= 3.0 months

> 3.0 months to <= 6.0 months

> 6.0 months

Male

Female

White

Black or African American

Other

< 5 kg

>= 5 kg

North American

Europe

Rest of World

MELODY

Pooled MELODY All Subjects AND Phase 2b Recommended Dose 

Efficacy through D151 for MA RSV LRTI by subgroup
14

Pooled MELODY All Subjects and Phase 2b Recommended Dose

Efficacy against MA LRTI for RSV A and RSV B through D151

Placebo

N=1293

Nirsevimab

N=2579 Efficacy

n % n % Efficacy 95% CI

RSV A 39 3.0 16 0.6 78.1 61.1-87.7

RSV B 41 3.2 15 0.6 80.0 63.7-89.0
2nd season RSV incidence D361 - D511 

after single dose prior to 1st season

MELODY (PRIMARY COHORT)
LRTI, lower respiratory tract infection; MA, medically attended; RSV, respiratory syncytial virus.

Very severe = hospitalization + requirement for supplemental oxygen and/or intravenous fluids

A low incidence of RSV LRTI was observed during 

season two with no hospitalized cases

Definition, n (%)

RSV Season 1 

(2019-2020):

To Day 151

RSV Season 2 

(2020-2021):

Days 361 – 511

Placebo

(n=496)

Nirsevimab

(n=994)

Placebo

(n=482)

Nirsevimab

(n=964)

MA RSV LRTI (protocoldefined) 25 (5.0) 12 (1.2) 2 (0.4) 7 (0.7)

MA RSV LRTI with 

hospitalization

(protocol-defined)

8 (1.6) 6 (0.6) 0 (0.0) 0 (0.0)

MA RSV LRTI (very severe) 7 (1.4) 5 (0.5) 0 (0.0) 0 (0.0)

Increasing severity

16 |
*Any medically attended LRTI; includes cases of MA RSV LRTI.

LRTI, lower respiratory tract infection; MA, medically attended; RSV, respiratory syncytial virus. 

Cases of any cause MA RSV LRTI were balanced by 

group

Definition, n (%)

RSV Season 1 

(2019-2020):

To Day 151

RSV Season 2 

(2020-2021):

Days 361 – 511

Placebo

(n=496)

Nirsevimab

(n=994)

Placebo

(n=482)

Nirsevimab

(n=964)

All MA LRTI (any cause)* 77 (15.5) 92 (9.3) 22 (4.6) 37 (3.8)

All MA respiratory illness with 

hospitalization (any cause)* 16 (3.2) 24 (2.4) 3 (0.6) 4 (0.4)

17 |
Duration of Protection
19

• Primary and secondary endpoints for MELODY evaluated the efficacy of 

nirsevimab through 150 days

• Efficacy did not decline over the time period of this evaluation

• There is some evidence that suggests that this protection extends beyond 

150 days although the degree of this protection is yet to be determined

• An analysis of the data from the South African cohort, that experienced a 

delayed RSV season, showed a hazard ratio of 0.491 (95% CI 0.158, 

1.523)

• Neutralizing antibody titers where 7x higher than baseline at day 361 in 

nirsevimab treated subjects and were significantly higher than those with 

natural infection

Duration of Protection
Implementation
Nirsevimab Vaccine-Like Implementation Can Provide Direct Protection of 

Infants for their first RSV Season

21

Protect infants born... Before the RSV season

April - October

During the RSV season

November to March

When Prior to start of the season At birth before hospital discharge

Where In office, during an existing well visit 

before the start of the season In hospital

How Intramuscular Injection with a Pre-Filled Syringe 

Similarity to Current 

Vaccine 

Implementation

Recommended Pediatric Immunizations 

administered during well visits* Birth Dose of Hepatitis B Vaccine*

Regardless of the time of year they are born 

*Birth-18 Years Immunization Schedule | CDC
Nirsevimab – Consistent Efficacy and Safety Across Studies/ 

Populations

22 |

• New data confirms safety and efficacy against medically attended RSV LRTI and 

hospitalization

• MELODY all subjects safety and efficacy against MA-LRTI is consistent with the primary cohort 

analysis

• MELODY all subjects analysis has demonstrated efficacy against hospitalization endpoints with an 

efficacy of 76.8% (49.4-89.4)

• Efficacy without waning over 150 days and suggestion of extended efficacy

• Safety profile favorable

• Low levels of reactogenicity

• Implementation of an all infant program for nirsevimab would be a combination of 

office administration for those born before the season and in-hospital administration 

for those born during the season

•
Thank You
24

Time to first RSV-confirmed MA LRTI in South Africa (ITT)

South Africa: Delayed Onset of RSV Season

Hazard ration (95% CI) = 0,491 (0.158, 1.523)

1.00

0.98

0.96

0.94

0.92

0.90

0.00

0 30 60 30 120 150 180 210 240 270 300 330 360

No. at Risk

Placebo

Nirsevimab

154 153 153 153 153 153 151 149 148 145 144 142 123

308 307 307 306 306 305 304 303 302 299 297 292 257

Time (days)

Proportion Free of Medically

Attended RSV LRTI

Placebo Nirsevimab

ITT population–participants from South Africa. Kaplan–Meier curve from a time-to-event analysis shows an estimate of the proportion of participants who were free from a medically attended RSV-associated LRTI. The hazard ratio and corresponding 

95% CIs were obtained from a proportional-hazard model. Tick marks indicate censored data. ITT, intent-to-treat.

• Unseasonal RSV transmission 

• South African participants remained 

unexposed to RSV until D151 due to 

COVID-19 pandemic1-2.

• Case differentials in RSV LRTI after D151 

is supportive of efficacy extended 

beyond 5 months1.

• 12 cases occurred up to 

Day 3611: 

• Nirsevimab: 6/308 (1.9%) 

• Placebo: 6/154 (3.9%)

MELODY Primary Cohort

1. Hammitt LL, et al. N Engl J Med. 2022;386:837-46. 2. Tempia S, et al. Euro Surveill. 2021;26(29):2001600.
RSV NAb levels higher in nirsevimab recipients versus placebo, 

regardless of presence or absence RSV infection

BL, baseline; GMC, geometric mean concentration; LLOQ, lower limit of quantification; with RSV, with confirmed RSV infection; without RSV, without 

confirmed RSV infection

MELODY

Nirsevimab with RSV

Nirsevimab without RSV

Placebo with RSV

Phase 2b Placebo without RSV

100

100000

10000

10

GMC RSV NAb, IU/mL

(95% CI)

BL 91 361

1000

Visit, days

151

100

100000

10000

10

GMC RSV NAb, IU/mL 

(95% CI)

BL 361

1000

Visit, days

31 151

• In nirsevimab recipients, RSV NAb levels vs baseline were >50 fold 

higher at Day 151 and ~7-fold higher at Day 361

• This suggests a level of protection extending beyond 5 months

n=737

n=21

n=37

n=347

n=433

n=29

n=31

LLOQ n=202 LLOQ
Phase 2b MELODY

1

1000

100

0.1

GMFR RSV NAb (95% 

CI)

BL 91 361

10

Visit, days

151

1

1000

100

0.1

GMFR RSV NAb (95% 

CI)

BL 361

10

Visit, days

31 151

LLOQ

BL, baseline; GMFR, geometric mean fold rise; LLOQ, lower limit of quantification; with RSV, with confirmed RSV infection; without RSV, without 

confirmed RSV infection

n=433

n=29

n=31

n=202

n=737

n=21

n=37

n=347

LLOQ

Nirsevimab with RSV

Nirsevimab without RSV

Placebo with RSV

Placebo without RSV

RSV NAb levels in infants with and without RSV infections

• In nirsevimab recipients, RSV NAb levels vs baseline were 

>50 fold higher at Day 151 and ~7-fold higher at Day 361
Potential Implementation of Nirsevimab for Routine Use

mAb, monoclonal antibody; mo, month; RSV, respiratory syncytial virus.

References: 1. American Academy of Pediatrics Periodicity schedule (updated March 2021) https://www.aap.org/periodicityschedule

[Accessed December 8, 2021]. 2. Janet S, et al. Hum Vaccin Immunother. 2018;14(1):234-244.

zzz

Nov Dec Jan Feb Mar

First RSV season

Birth month

Apr

May

Jun

Jul

Sep

Oct

Aug

In-season

births

Out-ofseason 

births

7mo

6mo

5mo

4mo

3mo

2mo

1mo

0mo

0mo

0mo

0mo

For infants born during RSV 

season administration during 

birth hospitalization

For infants born prior to RSV 

season administration in 

office/clinic during well child 

visit prior to season start

Nov

Dec

Jan

Feb

Mar 0mo

Birth month and age relative to RSV season and timing of administration 

27