Luxturna

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

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This medicinal product is subject to additional monitoring. This will allow quick identification of 

new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 

See section 4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT 
 

Luxturna 5 x 1012 vector genomes/mL concentrate and solvent for solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

2.1 General description 

 

Voretigene neparvovec is a gene transfer vector that employs an adeno-associated viral vector 

serotype 2 (AAV2) capsid as a delivery vehicle for the human retinal pigment epithelium 65 kDa 

protein (hRPE65) cDNA to the retina. Voretigene neparvovec is derived from naturally occurring 

AAV using recombinant DNA techniques. 

 

2.2 Qualitative and quantitative composition 

 

Each mL of concentrate contains 5 x 1012 vector genomes (vg). 

 

Each single-dose 2 mL vial of Luxturna contains 0.5 extractable mL of concentrate which requires a 

1:10 dilution prior to administration, see section 6.6. 

 

After dilution each dose of Luxturna contains 1.5 x 1011 vg in a deliverable volume of 0.3 mL. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Concentrate and solvent for solution for injection. 

 

Following thaw from their frozen state, both the concentrate and the solvent are clear, colourless 

liquids with a pH of 7.3. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Luxturna is indicated for the treatment of adult and paediatric patients with vision loss due to inherited 

retinal dystrophy caused by confirmed biallelic RPE65 mutations and who have sufficient viable 

retinal cells. 

 

4.2 Posology and method of administration 

 

Treatment should be initiated and administered by a retinal surgeon experienced in performing 

macular surgery. 

 



 

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Posology 

 

Patients will receive a single dose of 1.5 x 1011 vg voretigene neparvovec in each eye. Each dose will 

be delivered into the subretinal space in a total volume of 0.3 mL. The individual administration 

procedure to each eye is performed on separate days within a close interval, but no fewer than 6 days 

apart. 

 

Immunomodulatory regimen 

Prior to initiation of the immunomodulatory regimen and prior to administration of Luxturna, the 

patient must be checked for symptoms of active infectious disease of any nature, and in case of such 

infection the start of treatment must be postponed until after the patient has recovered. 

 

Starting 3 days prior to the administration of Luxturna to the first eye, it is recommended that an 

immunomodulatory regimen is initiated following the schedule below (Table 1). Initiation of the 

immunomodulatory regimen for the second eye should follow the same schedule and supersede 

completion of the immunomodulatory regimen of the first eye. 

 

Table 1 Pre- and post-operative immunomodulatory regimen for each eye 
 

Pre-operative 
3 days prior to Luxturna 

administration 

Prednisone (or equivalent) 

1 mg/kg/day 

(maximum of 40 mg/day) 

Post-operative 

4 days 

(including the day of 

administration) 

Prednisone (or equivalent) 

1 mg/kg/day 

(maximum of 40 mg/day) 

Followed by 5 days 

Prednisone (or equivalent) 

0.5 mg/kg/day 

(maximum of 20 mg/day) 

Followed by 5 days of one dose 

every other day 

Prednisone (or equivalent) 

0.5 mg/kg every other day 

(maximum of 20 mg/day) 

 

Special populations 

Elderly 

The safety and efficacy of voretigene neparvovec in patients ≥65 years old have not been established. 

However, no adjustment in dosage is necessary for elderly patients. 

 

Hepatic and renal impairment 

The safety and efficacy of voretigene neparvovec have not been established in patients with hepatic or 

renal impairment. No dose adjustment is required in these patients (see section 5.2). 

 

Paediatric population 

The safety and efficacy of voretigene neparvovec in children aged up to 4 years have not been 

established. No data are available. No adjustment in dosage is necessary for paediatric patients. 

 

Method of administration 

 

Subretinal use. 

 

Luxturna is a sterile concentrate solution for subretinal injection that requires thawing and dilution 

prior to administration (see section 6.6). 

 

This medicinal product must not be administered by intravitreal injection. 

 

Luxturna is a single-use vial for a single administration in one eye only. The product is administered 

as a subretinal injection after vitrectomy in each eye. It should not be administered in the immediate 

vicinity of the fovea to maintain foveal integrity (see section 4.4). 



 

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The administration of voretigene neparvovec should be carried out in the surgical suite under 

controlled aseptic conditions. Adequate anaesthesia should be given to the patient prior to the 

procedure. The pupil of the eye to be injected must be dilated and a broad-spectrum microbicide 

should be topically administered prior to the surgery according to standard medical practice. 

 

Precaution to be taken before manipulating or administering the medicinal product 

This medicinal product contains genetically modified organisms. Personal protective equipment (to 

include laboratory coat, safety glasses and gloves) should be worn while preparing or administering 

voretigene neparvovec (see section 6.6). 

 

For instructions for preparation, accidental exposure to and disposal of Luxturna, see section 6.6. 

 

Administration 

Follow the steps below to administer voretigene neparvovec to patients: 

 Diluted Luxturna should be inspected visually prior to administration. If particulates, 

cloudiness, or discoloration are visible, the medicinal product must not be used. 

 Connect the syringe containing the diluted product to the tubing and microcannula. The product 

is slowly injected through the tubing and microcannula to eliminate any air bubbles in the 

system. 

 The volume of product available for injection is confirmed in the syringe, by aligning the 

plunger tip with the line that marks 0.3 mL. 

 After vitrectomy is completed, Luxturna is administered by subretinal injection using a 

subretinal injection cannula introduced via pars plana (Figure 1A). 

 Under direct visualisation, the tip of the subretinal injection cannula is placed in contact with 

the retinal surface. The recommended site of injection should be located along the superior 

vascular arcade, at least 2 mm distal to the centre of the fovea (Figure 1B). A small amount of 

the product is slowly injected until an initial subretinal bleb is observed, and then the remaining 

volume is slowly injected until the total 0.3 mL is delivered. 

 

Figure 1A Subretinal injection cannula introduced via pars plana 
 

 
 



 

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Figure 1B Tip of the subretinal injection cannula placed within the recommended site of 

injection (surgeon’s view) 
 

 
 

 At the completion of the injection, the subretinal injection cannula is removed from the eye. 

 After injection, any unused product must be discarded. The back-up syringe may not be 

retained. Refer to local biosafety guidelines applicable for disposal of the product. 

 Fluid-air exchange is performed, carefully avoiding fluid drainage near the retinotomy created 

for the subretinal injection. 

 Supine head positioning is initiated immediately in the post-operative period and upon 

discharge should be maintained by the patient for 24 hours. 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1. 

Ocular or periocular infection. 

Active intraocular inflammation. 

 

4.4 Special warnings and precautions for use 

 

Proper aseptic techniques should always be used for the preparation and administration of Luxturna. 

 

The following adverse reactions have been observed with the administration procedure: 

 Eye inflammation (including endophthalmitis), retinal tear and retinal detachment. Patients 

should be instructed to report any symptoms suggestive of endophthalmitis or retinal 

detachment without delay and should be managed appropriately. 

 Retinal disorder (foveal thinning, loss of foveal function), macular hole, maculopathy (epiretinal 

membrane, macular pucker) and eye disorder (foveal dehiscence). 

 Increase in intraocular pressure. Intraocular pressure should be monitored prior to and following 

administration of the medicinal product and managed appropriately. Patients should be 

instructed to avoid air travel or other travel to high elevations until the air bubble formed as a 

result of administration of Luxturna has completely dissipated from the eye. A time period of up 

to one week or more following injection may be required before dissipation of the air bubble; 

this should be verified on ophthalmic examination. A rapid increase in altitude while the air 

bubble is still present can cause a rise in eye pressure and irreversible vision loss. 

 

Temporary visual disturbances, such as blurred vision and photophobia, may occur during the weeks 

that follow the treatment. Patients should be instructed to contact their healthcare professional if visual 

disturbances persist. Patients should avoid swimming because of an increased risk of infection in the 

eye. Patients should avoid strenuous physical activity because of an increased risk of injury to the eye. 

Patients may resume swimming and strenuous activity, after a minimum of one to two weeks, on the 

advice of their healthcare professional. 



 

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Shedding 

 

Transient and low-level vector shedding may occur in patient tears (see section 5.2). 

Patients/caregivers should be advised to handle waste material generated from dressings, tears and 

nasal secretion appropriately, which may include storage of waste material in sealed bags prior to 

disposal. These handling precautions should be followed for 14 days after administration of voretigene 

neparvovec. It is recommended that patients/caregivers wear gloves for dressing changes and waste 

disposal, especially in case of underlying pregnancy, breast-feeding and immunodeficiency of 

caregivers. 

 

Patients treated with Luxturna should not donate blood, organs, tissues and cells for transplantation. 

 

Immunogenicity 

 

To reduce the potential for immunogenicity patients should receive systemic corticosteroids before 

and after the subretinal injection of voretigene neparvovec to each eye (see section 4.2). The 

corticosteroids may decrease the potential immune reaction to either vector capsid (adeno-associated 

virus serotype 2 [AAV2] vector) or transgene product (retinal pigment epithelial 65 kDa protein 

[RPE65]). 

 

Sodium content 

 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 

‘sodium-free’. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

There are no known clinically significant interactions. No interaction studies have been performed. 

 

4.6 Fertility, pregnancy and lactation 
 

Based on non-clinical studies and clinical data from trials of AAV2 vectors, and considering the 

subretinal route of administration of Luxturna, inadvertent germ-line transmission with AAV vectors 

is highly unlikely. 

 

Pregnancy 

 

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of voretigene 

neparvovec in pregnant women. Animal studies do not indicate direct or indirect harmful effects with 

respect to reproductive toxicity (see section 5.3). 

 

As a precautionary measure, it is preferable to avoid the use of voretigene neparvovec during 

pregnancy. 

 

Breast-feeding 

 

Luxturna has not been studied in breast-feeding women. It is unknown whether voretigene neparvovec 

is excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be 

made whether to discontinue breast-feeding or to discontinue/abstain from voretigene neparvovec 

therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the 

woman. 

 

Fertility 

 

No clinical data on the effect of the medicinal product on fertility are available. Effects on male and 

female fertility have not been evaluated in animal studies. 



 

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4.7 Effects on ability to drive and use machines 
 

Voretigene neparvovec has minor influence on the ability to drive and use machines. Patients may 

experience temporary visual disturbances after receiving subretinal injection of Luxturna. Patients 

should not drive or use heavy machines until visual function has recovered sufficiently, as advised by 

their ophthalmologist. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

There were three non-serious adverse reactions of retinal deposits in three of 41 (7%) subjects that 

were considered to be related to voretigene neparvovec. All three of these events were a transient 

appearance of asymptomatic subretinal precipitates inferior to the retinal injection site, 1-6 days after 

injection and resolved without sequelae. 

 

Serious adverse reactions related to the administration procedure were reported in three subjects 

during the clinical programme. One of 41 (2%) subjects reported a serious event of intraocular 

pressure increased (secondary to administration of depo-steroid) that was associated with treatment for 

endophthalmitis related to the administration procedure and resulted in optic atrophy, and one of 41 

(2%) subjects reported a serious event of retinal disorder (loss of foveal function) that was assessed as 

related to the administration procedure. One of 41 (2%) subjects reported a serious event of retinal 

detachment that was assessed as related to the administration procedure. 

 

The most common adverse reactions (incidence ≥5%) related to the administration procedure were 

conjunctival hyperaemia, cataract, increased intraocular pressure, retinal tear, dellen, macular hole, 

subretinal deposits, eye inflammation, eye irritation, eye pain and maculopathy (wrinkling on the 

surface of the macula). 

 

Tabulated list of adverse reactions 

 

The adverse reactions are listed by system organ class and frequency using the following convention: 

very common (≥1/10), common ≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to 

<1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). 

 

Table 2 Adverse reactions related to voretigene neparvovec 
 

System organ class / 

Frequency 
Adverse reactions 

Eye disorders 

Common Retinal deposits 

 



 

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Table 3 Adverse reactions related to administration procedure 
 

System organ class / 

Frequency 
Adverse reactions 

Psychiatric disorders 

Common Anxiety 

Nervous system disorders 

Common Headache, dizziness 

Eye disorders 

Very common Conjunctival hyperaemia, cataract 

Common 

Retinal tear, dellen, macular hole, eye inflammation, eye irritation, eye 

pain, maculopathy, choroidal haemorrhage, conjunctival cyst, eye 

disorder, eye swelling, foreign body sensation in eyes, macular 

degeneration, endophthalmitis, retinal detachment, retinal disorder, 

retinal haemorrhage 

Not known Vitreous opacities* 

Gastrointestinal disorders 

Common Nausea, vomiting, abdominal pain upper, lip pain 

Skin and subcutaneous disorders 

Common Rash, swelling face 

Investigations 

Very common Intraocular pressure increased 

Common Electrocardiogram T wave inversion 

Injury, poisoning and procedural complications 

Common Endotracheal intubation complication, wound dehiscence 

*This adverse reaction has been reported spontaneously during post-marketing experience. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

There is no clinical experience with overdose of voretigene neparvovec. Symptomatic and supportive 

treatment, as deemed necessary by the treating physician, is advised in case of overdose. 

 

 

  



 

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5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Ophthalmologicals, other ophthalmologicals, ATC code: S01XA27. 

 

Mechanism of action 

 

The retinal pigment epithelium-specific 65 kilodalton protein (RPE65) is located in the retinal pigment 

epithelial cells and converts all-trans-retinol to 11-cis-retinol, which subsequently forms the 

chromophore, 11-cis-retinal, during the visual (retinoid) cycle. These steps are critical in the biological 

conversion of a photon of light into an electrical signal within the retina. Mutations in the RPE65 gene 

lead to reduced or absent RPE65 all-trans-retinyl isomerase activity, blocking the visual cycle and 

resulting in vision loss. Over time, accumulation of toxic precursors leads to the death of retinal 

pigment epithelial cells, and subsequently to progressive photoreceptor cell death. Individuals with 

biallelic RPE65 mutation-associated retinal dystrophy exhibit vision loss, including impaired visual 

function parameters such as visual acuity and visual fields often during childhood or adolescence; this 

loss of vision ultimately progresses to complete blindness. 

 

Injection of voretigene neparvovec into the subretinal space results in transduction of retinal pigment 

epithelial cells with a cDNA encoding normal human RPE65 protein (gene augmentation therapy), 

providing the potential to restore the visual cycle. 

 

Clinical efficacy and safety 

 

The long-term safety and efficacy of Luxturna were assessed in a Phase 1 safety and dose escalation 

study (101), in which 12 subjects received unilateral subretinal injections of voretigene neparvovec; a 

follow-on study (102) in which voretigene neparvovec was administered to the contralateral eye in 11 

of the 12 subjects who participated in the dose escalation study; a one-year, open-label Phase 3 

controlled study (301) in which 31 subjects were randomised at two sites; and the continuation of the 

Phase 3 study, in which the 9 control subjects crossed over and received the intervention. A total of 

41 subjects (81 eyes injected [one Phase 1 subject did not meet eligibility criteria for a second 

injection]) participated in the clinical programme. All participants had a clinical diagnosis of Leber 

congenital amaurosis, and some may have also had prior or additional clinical diagnoses, including 

retinitis pigmentosa. Confirmed biallelic RPE65 mutations and the presence of sufficient viable retinal 

cells (an area of retina within the posterior pole of >100 micron thickness, as estimated by optical 

coherence tomography [OCT]) were established for all participants. 

 

Phase 3 study 

Study 301 was an open-label, randomised, controlled study. 31 subjects were enrolled, 13 males and 

18 females. The average age was 15 years (range 4 to 44 years), including 64% paediatric subjects 

(n=20, age from 4 to 17 years) and 36% adults (n=11). All subjects had a diagnosis of Leber’s 

congenital amaurosis owing to RPE65 mutations confirmed by genetic analysis in a certified 

laboratory. 

 

21 subjects were randomised to receive subretinal injection of voretigene neparvovec. Visual acuity 

(LogMAR) of the first eye of these subjects at baseline was 1.18 (0.14), mean (SE). One subject 

discontinued from the study prior to treatment. 10 subjects were randomised to the control 

(non-intervention) group. Visual acuity (LogMAR) of the first eye of these subjects at baseline was 

1.29 (0.21), mean (SE). One subject in the control group withdrew consent and was discontinued from 

the study. The nine subjects who were randomised to the control group were crossed over to receive 

subretinal injection of voretigene neparvovec after one year of observation. Each eye was administered 

a single subretinal injection of 1.5 x 1011 vg voretigene neparvovec in a total volume of 300 μL. The 

interval between injection to the eyes for each subject was from 6 to 18 days. 

 



 

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The primary endpoint of the Phase 3 study measured the mean change from baseline to one year in 

binocular multi-luminance mobility testing (MLMT) between the intervention and control groups. The 

MLMT was designed to measure changes in functional vision, specifically the ability of a subject to 

navigate a course accurately and at a reasonable pace at different levels of environmental illumination. 

This ability depends on the subject’s visual acuity, visual field and the extent of nyctalopia (decreased 

ability to perceive and/or see in dim light), each of which are functions specifically affected by the 

retinal disease associated with RPE65 mutations. In the Phase 3 study, the MLMT used seven levels of 

illumination ranging from 400 lux to 1 lux (corresponding to, for example, a brightly lit office down to 

a moonless summer night). The testing of each subject was videotaped and assessed by independent 

graders. A positive change score reflects passing the MLMT at a lower light level and a lux score of 6 

reflects the maximum possible MLMT improvement. Three secondary endpoints were also tested: 

full-field light sensitivity threshold (FST) testing using white light; the change in MLMT score for the 

first assigned eye; and visual acuity (VA) testing. 

 

At baseline, subjects achieved pass marks on the mobility test at between 4 and 400 ambient lux. 

 

Table 4 Changes in MLMT score: year 1, compared to baseline (ITT population: n=21 

intervention, n=10 control) 
 

Change in MLMT score 

Difference 

(95% CI) 

Intervention-Control 

p-value 

using binocular vision 1.6 (0.72, 2.41) 0.001 

using assigned first eye only 1.7 (0.89, 2.52) 0.001 

using assigned second eye only 2.0 (1.14, 2.85) <0.001 

 

The monocular MLMT change score significantly improved in the treatment group and was similar to 

the binocular MLMT results (see Table 4). 

 

  



 

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Figure 2 shows the effect of the medicinal product over the three-year period in the voretigene 

neparvovec treatment group, as well as the effect in the control group after crossing over to receive 

subretinal injection of voretigene neparvovec. Significant differences in binocular MLMT 

performance were observed for the voretigene neparvovec treatment group at day 30 and were 

maintained over the remaining follow-up visits throughout the three-year period, compared to no 

change in the control group. However, after crossing-over to receive subretinal injection of voretigene 

neparvovec, the subjects in the control group showed a similar response to the voretigene neparvovec 

as compared to the subjects in the voretigene neparvovec treatment group. 

 

Figure 2 Change in MLMT score using binocular vision versus time before / after exposure to 

voretigene neparvovec 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
 

Each box represents the middle 50% of distribution of MLMT score change. Vertical dotted lines represent 

additional 25% above and below the box. The horizontal bar within each box represents the median. The dot 

within each box represents the mean. The solid line connects the mean MLMT score changes over visits for the 

treatment group. The dotted line connects the mean MLMT score change over visits for the control group, 

including five visits during the first year without receiving voretigene neparvovec. The control group was 

administered voretigene neparvovec after 1 year of observation. 

BL: baseline; 

D30, D90, D180: 30, 90 and 180 days after start of study; 

Y1, Y2, Y3: one, two and three years after start of study; 

XBL; XD30; XD90; XD180: baseline, 30, 90 and 180 days after start of study for control crossover group; 

XY1; XY2: one and two years after start of study for control crossover group. 

 

BL D30 D90 D180 Y1 Y2 Y3 
XBL XD30 XD90 XD180 XY1 XY2 



 

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Results of full-field light sensitivity testing at the first study year: white light [Log10(cd.s/m2)] are 

shown in Table 5 below. 

 

Table 5 Full-field light sensitivity testing 
 

Full-field light sensitivity testing – First assigned eye (ITT) 

 Intervention, N = 21 

Baseline Year 1 Change 

N 20 20 19 

Mean (SE) -1.23 (0.10) -3.44 (0.30) -2.21 (0.30) 

 

 Control, N = 10 

N 9 9 9 

Mean (SE) -1.65 (0.14) -1.54 (0.44) 0.12 (0.45) 

 Difference (95% CI) (Intervention-Control) 

-2.33 (-3.44, -1.22), p<0.001 

Full-field light sensitivity testing – Second assigned eye (ITT) 

 Intervention, N = 21 

Baseline Year 1 Change 

N 20 20 19 

Mean (SE) -1.35 (0.09) -3.28 (0.29) -1.93 (0.31) 

 

 Control, N = 10 

N 9 9 9 

Mean (SE) -1.64 (0.14) -1.69 (0.44) 0.04 (0.46) 

 Difference (95% CI) (Intervention-Control) 

-1.89 (-3.03, -0.75), p=0.002 

Full-field light sensitivity testing - Averaged across both eyes (ITT) 

Difference (95% CI) (Intervention-Control): -2.11 (-3.19, -1.04), p<0.001 

 

Improvement in full-field light sensitivity was maintained for up to 3 years after exposure to 

voretigene neparvovec. 

 

At one year after exposure to voretigene neparvovec, improvement in visual acuity of at least 

0.3 LogMAR occurred in 11/20 (55%) of the first-treated eyes and 4/20 (20%) of the second-treated 

eyes in the intervention group; no one in the control group displayed such an improvement of visual 

acuity in either the first or second eye. 

 

5.2 Pharmacokinetic properties 

 

Voretigene neparvovec is expected to be taken up by cells through heparin sulphate proteoglycan 

receptors and be degraded by endogenous proteins and DNA catabolic pathways. 

 

Nonclinical biodistribution 

 

Biodistribution of Luxturna was evaluated at three months following subretinal administration in 

non-human primates. The highest levels of vector DNA sequences were detected in intraocular fluids 

(anterior chamber fluid and vitreous) of vector-injected eyes. Low levels of vector DNA sequences 

were detected in the optic nerve of the vector-injected eye, optic chiasm, spleen and liver, and 

sporadically in the stomach and lymph nodes. In one animal administered with Luxturna at 

7.5 x 1011 vg (5 times the recommended per eye dose), vector DNA sequences were detected in colon, 

duodenum and trachea. Vector DNA sequences were not detected in gonads. 

 



 

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Clinical pharmacokinetics and shedding 

 

The vector shedding and biodistribution were evaluated in tears from both eyes, serum and whole 

blood of subjects in the Phase 3 clinical study. In 13/29 (45%) subjects receiving bilateral 

administrations, Luxturna vector DNA sequences were detected in tear samples; most of these subjects 

were negative after the day 1 post-injection visit, however, four of these subjects had positive tear 

samples beyond the first day, one subject up to day 14 post-second eye injection. Vector DNA 

sequences were detected in serum in 3/29 (10%) subjects, including two with positive tear samples, 

and only up to day 3 following each injection. Overall, transient and low levels of vector DNA were 

detected in tear and occasional serum samples from 14/29 (48%) of subjects in the Phase 3 study. 

 

Pharmacokinetics in special populations 

 

No pharmacokinetic studies with voretigene neparvovec have been conducted in special populations. 

 

Hepatic and renal impairment 

Luxturna is injected directly into the eye. Liver and kidney function, cytochrome P450 polymorphisms 

and ageing are not expected to influence the clinical efficacy or safety of the product. Therefore, no 

adjustment in dosage is necessary for patients with hepatic or renal impairment. 

 

5.3 Preclinical safety data 
 

Ocular histopathology of dog and non-human primate eyes exposed to voretigene neparvovec showed 

only mild changes, which were mostly related to healing from surgical injury. In an earlier toxicology 

study, a similar AAV2 vector administered subretinally in dogs at a dose of 10 times the 

recommended dose resulted in focal retinal toxicity and inflammatory cell infiltrates histologically in 

regions exposed to the vector. Other findings from voretigene neparvovec non-clinical studies 

included occasional and isolated inflammatory cells in the retina, with no apparent retinal 

degeneration. Following a single vector administration, dogs developed antibodies to the AAV2 vector 

capsid which were absent in naïve non-human primates. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Concentrate 

 

Sodium chloride 

Sodium dihydrogen phosphate monohydrate (for pH adjustment) 

Disodium hydrogen phosphate dihydrate (for pH adjustment) 

Poloxamer 188 

Water for injections 

 

Solvent 

 

Sodium chloride 

Sodium dihydrogen phosphate monohydrate (for pH adjustment) 

Disodium hydrogen phosphate dihydrate (for pH adjustment) 

Poloxamer 188 

Water for injections 

 

6.2 Incompatibilities 
 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 

products. 

 



 

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6.3 Shelf life 
 

Unopened frozen vials 

 

2 years 

 

After thawing and dilution 

 

Once thawed, the medicinal product should not be re-frozen and be left at room temperature (below 

25 °C). 

 

Following dilution under aseptic conditions, the solution must be used immediately; if not used 

immediately, the storage time at room temperature (below 25 °C) should be no longer than 4 hours. 

 

6.4 Special precautions for storage 

 

Concentrate and solvent must be stored and transported frozen at ≤-65 ºC. 

 

For storage conditions after thawing and dilution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

0.5 mL extractable volume of concentrate in 2 mL cyclic olefin polymer vial with a chlorobutyl rubber 

stopper sealed in place with an aluminium flip-off seal. 

 

1.7 mL extractable volume of solvent in a 2 mL cyclic olefin polymer vial with a chlorobutyl rubber 

stopper sealed in place with an aluminium flip-off seal. 

 

Each foil pouch includes a carton containing 1 vial of concentrate and 2 vials of solvent. 

 

6.6 Special precautions for disposal and other handling 
 

Each carton containing 1 vial of concentrate and 2 vials of solvent is for single use only. 

 

Luxturna should be inspected visually prior to administration. If particulates, cloudiness, or 

discoloration are visible, the single-dose vial must not be used. 

 

Accidental exposure must be avoided. Local biosafety guidelines for preparation, administration and 

handling of voretigene neparvovec should be followed. 

 Personal protective equipment (to include laboratory coat, safety glasses and gloves) should be 

worn while preparing or administering voretigene neparvovec. 

 Accidental exposure to voretigene neparvovec, including contact with skin, eyes and mucous 

membranes, is to be avoided. Any exposed wounds should be covered before handling. 

 All spills of voretigene neparvovec must be treated with a virucidal agent such as 1% sodium 

hypochlorite and blot using absorbent materials. 

 All materials that may have come in contact with voretigene neparvovec (e.g. vial, syringe, 

needle, cotton gauze, gloves, masks or dressings) must be disposed of in accordance with local 

biosafety guidelines. 

 

Accidental exposure 

 

 In the event of an accidental occupational exposure (e.g. through a splash to the eyes or mucous 

membranes), flush with clean water for at least 5 minutes. 

 In the event of exposure to broken skin or needlestick injury, clean the affected area thoroughly 

with soap and water and/or a disinfectant. 

 



 

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This medicinal product contains genetically modified organisms. Unused medicinal product must be 

disposed of in compliance with the local biosafety guidelines. 

 

Preparation 

 

Preparation of Luxturna should be performed within 4 hours of beginning the administration 

procedure, in accordance with the following recommended procedure performed under aseptic 

conditions. 

 

Thaw one single-dose vial of concentrate and two vials of solvent at room temperature. Gently invert 

the vials five times to mix the contents. 

 

Inspect for any visual particulates or any anomalies. Any anomalies or appearance of visual 

particulates should be reported to the Marketing Authorisation Holder and product should not be used. 

 

Transfer 2.7 mL of solvent taken from the two thawed vials and dispense into a sterile 10 mL empty 

glass vial using a 3 mL syringe. 

 

For dilution, draw 0.3 mL of thawed concentrate into a 1 mL syringe and add it to the 10 mL sterile 

vial containing the solvent. Gently invert the vial at least five times for proper mixing. Inspect for any 

visual particulates. The diluted solution should be clear to slightly opalescent. Label the 10 mL glass 

vial containing the diluted concentrate as follows: ‘Diluted Luxturna’. 

 

Do not prepare syringe if the vial shows any damage or if any visual particulates are observed. Prepare 

the syringes for injection by drawing 0.8 mL of the diluted solution into a sterile 1 mL syringe. Repeat 

the same procedure to prepare a backup syringe. The product-filled syringes should then be transferred 

in a designated transport container to the surgical suite. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/18/1331/001 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

22 November 2018 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

  



 

16 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 

SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 

BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 



 

17 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer of the biological active substance 

 

Spark Therapeutics Inc. 

3737 Market Street, Suite 1300 

Philadelphia 

PA19104 

United States 

 

Name and address of the manufacturer responsible for batch release 

 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nuremberg 

Germany 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports 

 

The requirements for submission of periodic safety update reports for this medicinal product are 

set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 

Directive 2001/83/EC and any subsequent updates published on the European medicines web-

portal. 

 

The marketing authorisation holder shall submit the first periodic safety update report for this product 

within 6 months following authorisation. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk Management Plan (RMP) 

 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in 

the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 

subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 



 

18 

 Additional risk minimisation measures 

 

Prior to launch of LUXTURNA in each Member State the Marketing Authorisation Holder (MAH) 

must agree about the content and format of the educational programme, including communication 

media, distribution modalities, and any other aspects of the programme, with the National Competent 

Authority (NCA). 

 

The MAH shall ensure that in each Member State (MS) where LUXTURNA is marketed, the product 

is distributed through treatment centres where qualified staff (i.e. vitreoretinal surgeons and 

pharmacists) have participated in the mandatory educational program about use of the product and 

pharmacy training, in order to ensure LUXTURNA correct use so as to minimise the risks associated 

with its administration and/or the administration procedure (increased intraocular pressure, retinal tear, 

macular disorders, cataract, intraocular inflammation and/or infection related to the procedure and 

retinal detachment, third party transmission). 

 

Criteria for Study sites/treatment centres should include: 

1. Presence of a specialist ophthalmologist with expertise in care and treatment of patients with 

inherited retinal dystrophy (IRD); 

2. Presence  of or affiliation with a retinal surgeon experienced in sub-retinal surgery and capable 

of administrating LUXTURNA; 

3. Presence of a clinical pharmacy capable of handling and preparing AAV vector-based gene 

therapy products; 

 

Training and instructions for safe handling and disposal of affected materials for 14 days following 

product administration should also be provided along with information regarding exclusion from 

donation of blood, organs, tissues, and cells for transplantation after LUXTURNA administration. 

 

The qualified staff (i.e. vitreoretinal surgeons and pharmacists) at the treatment centres should be 

provided with educational materials including: 

 Summary of Product Characteristics (SmPC); 

 Surgical education for LUXTURNA administration, including description of materials and 

procedures needed to perform LUXTURNA subretinal injection 

or 

 Pharmacy training manual, including information on LUXTURNA preparation and storage; 

 

Patients and their caregivers should be provided with the patient information pack, including: 

 Patient Information Leaflet (PIL), which should also be available in alternative formats 

(including large print and as audio file); 

 A patient card 

o Highlights the importance of follow-up visits and reporting side effects to the patient’s 

physician. 

o Inform healthcare professionals that the patient has received gene therapy, and the 

importance of reporting adverse events. 

o Contact information for adverse event reporting. 

o Patient card will be available in alternative formats including large print and as an audio 

file. Information on how to obtain the special formats will be provided in the patient card. 

 



 

19 

 Obligation to conduct post-authorisation measures 

 

The MAH shall complete, within the stated timeframe, the below measures: 

 

Description Due date 

SPKRPE-EUPASS: Non-interventional PASS: In order to further characterise 

the safety including long-term safety of Luxturna, the applicant should 

conduct and submit a study based on data from a disease registry in patients 

vision loss due to inherited retinal dystrophy caused by confirmed biallelic 

RPE65 mutations. 

30 June 2030 

AAV2-hRPE65v2-LTFU-01: In order to further evaluate the long-term 

efficacy and safety outcomes of Luxturna in adult and paediatric patients with 

vision loss due to inherited retinal dystrophy caused by confirmed biallelic 

RPE65 mutations, the applicant should submit the long-term efficacy and 

safety follow-up of trial participants who received Luxturna in the clinical 

programme (15-year follow-up). 

31 December 

2031 

 

  



 

20 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



 

21 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



 

22 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

POUCH 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Luxturna 5 x 1012 vector genomes/mL concentrate and solvent for solution for injection 

voretigene neparvovec 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each mL of concentrate contains 5 x 1012 vector genomes of voretigene neparvovec. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen 

phosphate dihydrate, poloxamer 188, water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Concentrate and solvent for solution for injection 

 

1 vial concentrate 

2 vials solvent 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For single administration by subretinal injection into one (1) eye. 

Dilute before use. 

Read the package leaflet before use. 

Subretinal use after dilution. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



 

23 

9. SPECIAL STORAGE CONDITIONS 

 

Store and transport frozen at ≤-65 ºC. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Discard unused product. 

This medicine contains genetically modified organisms. 

Unused medicine must be disposed of in compliance with the local biosafety guidelines. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/18/1331/001 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



 

24 

 

PARTICULARS TO APPEAR ON THE INTERMEDIATE PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Luxturna 5 x 1012 vector genomes/mL concentrate and solvent for solution for injection 

voretigene neparvovec 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each mL of concentrate contains 5 x 1012 vector genomes of voretigene neparvovec. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen 

phosphate dihydrate, poloxamer 188, water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Concentrate and solvent for solution for injection 

 

1 vial concentrate 

2 vials solvent 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For single administration by subretinal injection into one (1) eye. 

Dilute before use. 

Read the package leaflet before use. 

Subretinal use after dilution. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



 

25 

9. SPECIAL STORAGE CONDITIONS 

 

Store and transport frozen at ≤-65 ºC. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Discard unused product. 

This medicine contains genetically modified organisms. 

Unused medicine must be disposed of in compliance with the local biosafety guidelines. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/18/1331/001 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

  



 

26 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL (CONCENTRATE) 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Luxturna 5 x 1012 vector genomes/mL concentrate for solution for injection 

voretigene neparvovec 

Subretinal use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

Single-dose vial, 0.5 mL extractable volume 

 

 

6. OTHER 

 

Dilute before use. 

Discard unused product. 

Store at ≤-65 ºC. 

  



 

27 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL (SOLVENT) 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Solvent for Luxturna 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

1.7 mL extractable volume 

 

 

6. OTHER 

 

Store at ≤-65 ºC. 

  



 

28 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 

29 

Package leaflet: Information for the patient 

 

Luxturna 5 x 1012 vector genomes/mL concentrate and solvent for solution for injection 

voretigene neparvovec 

 

This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 

for how to report side effects. 

 

Read all of this leaflet carefully before you are given this medicine because it contains important 

information for you. 
- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or nurse. 

- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 

 

What is in this leaflet: 

 

1. What Luxturna is and what it is used for 

2. What you need to know before you are given Luxturna 

3. How Luxturna is given to you 

4. Possible side effects 

5. How Luxturna is stored 

6. Contents of the pack and other information 

 

 

1. What Luxturna is and what it is used for 

 

Luxturna is a gene therapy product that contains the active substance voretigene neparvovec. 

 

Luxturna is used for the treatment of adults and children with vision loss due to inherited retinal 

dystrophy caused by mutations in the RPE65 gene. These mutations prevent the body from producing 

a protein needed for vision and so lead to loss of sight and eventual blindness. 

 

The active substance in Luxturna, voretigene neparvovec, is a modified virus that contains a working 

copy of the RPE65 gene. After injection it delivers this gene into the cells of the retina, the layer at the 

back of the eye that detects light. This enables the retina to produce the proteins needed for vision. The 

virus used to deliver the gene does not cause disease in humans. 

 

Luxturna will be given to you only if genetic testing shows that your vision loss is caused by 

mutations in the RPE65 gene. 

 

 

2. What you need to know before you are given Luxturna 

 

You will not be given Luxturna 

- if you are allergic to voretigene neparvovec or any of the other ingredients of this medicine 

(listed in section 6) 

- if you have an eye infection 

- if you have eye inflammation 

 

If any of the above applies to you, or if you are unsure of any of the above, please talk to your doctor 

before you receive Luxturna. 

 



 

30 

Warnings and precautions 

Before receiving treatment with Luxturna: 

 Tell your doctor if you have signs of an eye infection or eye inflammation, for example if you 

have eye redness, sensitivity to light, eye swelling or eye pain. 

 Tell your doctor if you have an active infection of any sort. Your doctor may delay your 

treatment until your infection is gone because this medicine may make it more difficult for you 

to fight an infection. See also section 3. 

 

After receiving Luxturna: 

 Get immediate care from your doctor if your eye or eyes become red, painful, sensitive to light, 

you see flashes or floaters in your vision, or if you notice any worsening or blurred vision. 

 You should avoid air travel or other travel to high elevations until advised by your doctor. 

During treatment with this medicine, the doctor inserts an air bubble in the eye, which is slowly 

absorbed by your body. Until the bubble is fully absorbed, air travel or other travel to high 

elevations may make the bubble expand and lead to eye damage, including vision loss. Please 

talk to your doctor before travelling. 

 You should avoid swimming because of an increased risk of infection in the eye. Please talk to 

your doctor before going to swim after receiving treatment with Luxturna. 

 You should avoid strenuous physical activity because of an increased risk of injury to the eye. 

Please talk to your doctor before beginning to engage in strenuous physical activity after 

receiving Luxturna. 

 Some people develop cataracts. A cataract is clouding of the natural lens inside the eye that can 

make it harder to see clearly. The development or worsening of cataracts is a known 

complication of the eye surgery that will be required before you receive Luxturna. There is an 

additional risk of cataract if the lens inside the eye is damaged by the needle used to inject the 

medicine into the back of the eye. 

 You may have temporary visual disturbances, such as light sensitivity, and blurred vision. Tell 

your doctor about any visual disturbances that you experience. Your doctor may be able to help 

reduce any discomfort caused by these temporary disturbances. 

 Some medicine may be present in your tears. You and your caregiver should place any used 

dressings and waste material with tears and nasal secretions in sealed bags before disposing of 

them. You should follow these precautions for 14 days. 

 You and your caregiver, especially if pregnant, breast-feeding or with a suppressed immune 

system, should wear gloves during dressing changes and when disposing of the dressings and 

other waste material. Follow these precautions for 14 days after the treatment. 

 You will not be able to donate blood, organs, tissues and cells for transplantation after you have 

been treated with Luxturna. This is because Luxturna is a gene therapy product. 

 

Children and adolescents 

Luxturna has not been studied in children under four years of age. 

 

Other medicines and Luxturna 

Please tell your doctor if you are taking, have recently taken or might take any other medicines. 

 

Pregnancy and breast-feeding and fertility 

If you are pregnant or breast-feeding, think you might be pregnant, or are planning to have a baby, ask 

your doctor or nurse for advice before being treated with Luxturna. 

 

The effects of this medicine on pregnancy and the unborn child are not known. As a precaution, you 

should not receive Luxturna while you are pregnant. 

 

Luxturna has not been studied in breast-feeding women. It is not known whether it passes into breast 

milk. Ask your doctor whether you should stop breast-feeding after receiving Luxturna. 

 

There is no information on the effect of Luxturna on male or female fertility. 

 



 

31 

Driving and using machines 

You may have temporary visual disturbances after receiving Luxturna. Do not drive or use heavy 

machines until your vision has recovered. Talk to your doctor before resuming these activities. 

 

Important information about some of the ingredients of Luxturna 

Luxturna contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’. 

 

 

3. How Luxturna is given to you 

 

Luxturna will be given to you in an operating room by surgeons experienced in performing eye 

surgery. 

 

Luxturna is given under anaesthesia. Your doctor will talk to you about the anaesthesia and how it will 

be given to you. 

 

Your doctor will carry out eye surgery to remove the clear gel inside the eye, and then inject Luxturna 

directly under your retina, the thin light-sensing layer at the back of that eye. This will be repeated on 

your other eye at least 6 days afterwards. You will need to stay for post-operative observation for a 

few hours after each procedure to monitor your recovery and watch for any side effects from the 

surgery or the anaesthesia. 

 

Before Luxturna treatment is started, your doctor may prescribe a medicine that will suppress your 

immune system (the body’s natural defences) so that it will not try to fight the Luxturna when it is 

given. It is important that you take this medicine according to the instructions given. Do not stop 

taking the medicine without first talking to your doctor. 

 

If you are given more Luxturna than you should be 

As this medicine is given to you by a doctor, it is unlikely that you will be given too much. If it does 

occur, your doctor will treat the symptoms as necessary. Tell your doctor or nurse if you have any 

visual problems. 

 

If you have any further questions on the use of this medicine, ask your doctor or nurse. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

The following side effects may happen with Luxturna: 

 

Common (may affect up to 1 in 10 people) 

 Deposits under the retina 

 

The following side effects may happen with the injection procedure: 

 

Very common (may affect more than 1 in 10 people) 

 Redness of the eye 

 Cataract (clouding of the lens) 

 Increased pressure in the eye 

 

  



 

32 

Common (may affect up to 1 in 10 people) 

 Break in the retina 

 Eye pain 

 Eye swelling 

 Detachment of the retina 

 Nausea (feeling sick), vomiting, abdominal (belly) pain, lip pain 

 Change of the electrical activity of the heart 

 Headache, dizziness 

 Rash, facial swelling 

 Anxiety 

 Problems associated with the placement of a breathing tube in the windpipe 

 Breakdown of the surgical wound 

 

Not known (frequency cannot be estimated from the available data) 

 Clouding in the gel-like substance inside the eye (vitreous opacities) 

 

Damage to the tissues of the eye may be accompanied by bleeding and swelling and an increased risk 

of infection. There is reduced vision in the days after surgery that usually improves; tell your doctor if 

vision does not return. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via the national reporting system listed in  

Appendix V. By reporting side effects, you can help provide more information on the safety of this 

medicine. 

 

 

5. How Luxturna is stored 

 

Luxturna will be stored by the healthcare professionals at your healthcare facility. 

Concentrate and solvent must be stored and transported frozen at ≤-65 ºC. Once thawed, the medicine 

should not be re-frozen and should be left at room temperature (below 25 °C). 

Do not use this medicine after the expiry date which is stated on the label and carton after EXP. 

 

 

6. Contents of the pack and other information 

 

What Luxturna contains 

- The active substance is voretigene neparvovec. Each mL of concentrate contains 5 x 1012 vector 

genomes (vg). The concentrate (0.5 mL extractable volume in a single-dose 2 mL vial) requires 

a 1:10 dilution prior to administration. 

- Each dose of diluted solution contains 1.5 x 1011 vector genomes of voretigene neparvovec in a 

deliverable volume of 0.3 mL. 

- The other ingredients of the concentrate are sodium chloride (see end of section 2), sodium 

dihydrogen phosphate monohydrate (for pH adjustment), disodium hydrogen phosphate 

dihydrate (for pH adjustment), poloxamer 188 and water for injections. 

- The solvent contains sodium chloride (see end of section 2), sodium dihydrogen phosphate 

monohydrate (for pH adjustment), disodium hydrogen phosphate dihydrate (for pH adjustment), 

poloxamer 188 and water for injections. 

 

What Luxturna looks like and contents of the pack 

Luxturna is a clear, colourless concentrate for solution for subretinal injection, supplied in a clear 

plastic vial. The solvent is a clear, colourless liquid supplied in a clear plastic vial. 

 

Each foil pouch includes a carton containing 1 vial of concentrate and 2 vials of solvent. 

 



 

33 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 

SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел: +359 2 489 98 28 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 

Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 

Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 



 

34 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 

 

Other sources of information 
This leaflet is available as an audio file and in a large print from the web site: 

http://www.voretigeneneparvovec.support 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu. 

 

 

------------------------------------------------------------------------------------------------------------------------ 

 

The following information is intended for healthcare professionals only: 

 

Instructions for preparation, accidental exposure and disposal of Luxturna 

 

Each carton containing 1 vial of concentrate and 2 vials of solvent is for single use only. 

 

Accidental exposure must be avoided. Local biosafety guidelines for preparation, administration and 

handling of Luxturna should be followed. 

- Personal protective equipment (to include laboratory coat, safety glasses and gloves) should be 

worn while preparing or administering voretigene neparvovec. 

- Accidental exposure to voretigene neparvovec, including contact with skin, eyes and mucous 

membranes, is to be avoided. Any exposed wounds should be covered before handling. 

- Treat all Luxturna spills with a virucidal agent such as 1% sodium hypochlorite and blot using 

absorbent materials. 

- All materials that may have come in contact with Luxturna (e.g. vial, syringe, needle, cotton 

gauze, gloves, masks or dressings) must be disposed of in accordance with local biosafety 

guidelines. 

 

  



 

35 

Accidental exposure 

 

- In the event of an accidental occupational exposure (e.g. through a splash to the eyes or mucous 

membranes), flush with clean water for at least 5 minutes. 

- In the event of exposure to broken skin or needlestick injury, clean the affected area thoroughly 

with soap and water and/or a disinfectant. 

 

This medicine contains genetically modified organisms. Unused medicinal product must be disposed 

of in compliance with the local biosafety guidelines. 

 

Preparation 

 

Preparation of Luxturna should be performed, within 4 hours of beginning the administration 

procedure, in accordance with the following recommended procedures performed under aseptic 

conditions. 

 

Thaw one single-dose vial of concentrate and two single-use vials of solvent at room temperature. 

Gently invert the thawed solvent vials five times to mix the contents. 

 

Inspect for any visual particulates. Any anomalies or appearance of visual particulates should be 

reported to the Marketing Authorisation Holder and product should not be used. 

 

Transfer 2.7 mL of the solvent taken from the two thawed vials and dispense into a sterile 10 mL glass 

vial using a 3 mL syringe. 

 

For dilution, transfer 0.3 mL of thawed concentrate into a 1 mL syringe and add it to the 10 mL sterile 

vial containing the solvent. Gently invert the 10 mL glass vial at least five times for proper mixing. 

Label the 10 mL glass vial containing the diluted concentrate as follows: ‘Diluted Luxturna’. 

 

Do not prepare syringes for injection if the vials show any damage or if any visual particulates are 

observed. Prepare the syringes for injection by drawing 0.8 mL of the diluted solution into each sterile 

1 mL syringe. The product filled syringes should then be transferred in a designated transport 

container to the surgical suite. 

 

Posology 

 

Treatment should be initiated and administered by a retinal surgeon experienced in performing 

macular surgery. 

 

Luxturna is a single-use vial for a single administration in one eye only. Each single dose of 

1.5 x 1011 vg will be delivered into the subretinal space in a total volume of 0.3 mL per eye. The 

individual administration procedure to each eye should be performed on separate days within a close 

interval, but no fewer than 6 days apart. 

 

Immunomodulatory regimen 

Prior to initiation of the immunomodulatory regimen and prior to administration of Luxturna, the 

patient must be checked for symptoms of active infectious disease of any nature, and in case of such 

infection the start of treatment must be postponed until after the patient has recovered. 

 

Starting 3 days prior to the administration of Luxturna to the first eye, it is recommended that an 

immunomodulatory regimen is initiated following the schedule below (Table 1). Initiation of the 

immunomodulatory regimen for the second eye should follow the same schedule and supersede 

completion of the immunomodulatory regimen of the first eye. 

 



 

36 

Table 1 Pre- and post-operative immunomodulatory regimen for each eye 
 

Pre-operative 
3 days prior to Luxturna 

administration 

Prednisone (or equivalent) 

1 mg/kg/day 

(maximum of 40 mg/day) 

Post-operative 

4 days 

(including the day of 

administration) 

Prednisone (or equivalent) 

1 mg/kg/day 

(maximum of 40 mg/day) 

Followed by 5 days 

Prednisone (or equivalent) 

0.5 mg/kg/day 

(maximum of 20 mg/day) 

Followed by 5 days of one dose 

every other day 

Prednisone (or equivalent) 

0.5 mg/kg every other day 

(maximum of 20 mg/day) 

 

Special populations 

Elderly 

The safety and efficacy of voretigene neparvovec in patients ≥65 years old have not been established. 

However, no adjustment in dosage is necessary for elderly patients. 

 

Hepatic and renal impairment 

The safety and efficacy of voretigene neparvovec have not been established in patients with hepatic or 

renal impairment. No dose adjustment is required in these patients (see section 5.2). 

 

Paediatric population 

The safety and efficacy of voretigene neparvovec in children aged up to 4 years have not been 

established. No data are available. No adjustment in dosage is necessary for paediatric patients. 

 

Method of administration 

 

Subretinal use. 

 

Luxturna is a concentrate for solution for subretinal injection that requires thawing and dilution prior 

to administration. 

 

This medicinal product must not be administered by intravitreal injection. 

 

The product is administered as a subretinal injection after vitrectomy in each eye. It should not be 

administered in the immediate vicinity of the fovea to maintain foveal integrity. 

 

The administration of voretigene neparvovec should be carried out in the surgical suite under 

controlled aseptic conditions. Adequate anaesthesia should be given prior to the procedure. The pupil 

of the eye to be injected must be dilated, and a broad-spectrum microbiocide should be topically 

administered prior to the surgery according to standard medical practice. 

 

Precaution to be taken before manipulating or administering the product 

Personal protective equipment (to include laboratory coat, safety glasses and gloves) should be worn 

while preparing or administering voretigene neparvovec. 

 

Intraocular pressure should be monitored prior to and following administration of the product, and 

managed appropriately. 

 

Following the administration, patients should be instructed to report any symptoms suggestive of 

retinal detachment or endophthalmitis without delay and should be managed appropriately. 

 



 

37 

Follow the steps below to administer Luxturna to patients: 

 Diluted Luxturna should be inspected visually prior to administration. If particulates, 

cloudiness, or discoloration are visible, the product must not be used. 

 Connect the syringe containing the diluted product to the extension tube and subretinal injection 

cannula. The product is slowly injected through the extension tube and subretinal injection 

cannula to eliminate any air bubbles. 

 The volume of product available for injection is confirmed in the syringe, by aligning the 

plunger tip with the line that marks 0.3 mL. 

 After vitrectomy is completed, Luxturna is administered by subretinal injection using a 

commercially available subretinal injection cannula introduced via pars plana. 

 Under direct visualisation, the tip of the subretinal injection cannula is placed in contact with 

the retinal surface. The recommended site of injection is located along the superior vascular 

arcade, at least 2 mm distal to the centre of the fovea. A small amount of the product is slowly 

injected until an initial subretinal bleb is observed, and then, the remaining volume is slowly 

injected until the total 0.3 mL is delivered (Figure 1). 

 

Figure 1 Tip of the subretinal injection cannula placed within recommended injection site 

(surgeon’s view) 
 

 
 

 At the completion of the injection, the subretinal injection cannula is removed from the eye. 

 Fluid-air exchange is performed, carefully avoiding fluid drainage near the retinotomy created 

for the subretinal injection. 

 Supine head positioning is initiated immediately in the post-operative period and, upon 

discharge, patients should be advised to rest in a supine position as much as possible for 

24 hours. 

After injection, any unused product must be discarded. The back-up syringe may not be 

retained. Refer to local biosafety guidelines applicable for disposal of the product. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET