Voretigene Neparvovec

LUXTURNA is designed to deliver a normal copy of the gene encoding the human retinoid isomerohydrolase RPE65 (RPE65) to cells of the retina in persons with reduced or absent levels of biologically active RPE65. The RPE65 is produced in the retinal pigment epithelial (RPE) cells and converts all- trans -retinol to 11- cis -retinol, which subsequently forms the chromophore, 11- cis -retinal, during the visual (retinoid) cycle.

• LUXTURNA (voretigene neparvovec-rzyl) is an adeno-associated virus vector-based gene therapy indicated for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. Patients must have viable retinal cells as determined by the treating physician(s).

• None. None.contraindicated

For subretinal injection only. The recommended dose of LUXTURNA for each eye is 1.5 x 10 11 vector genomes (vg), administered by subretinal injection in a total volume of 0.3 mL. (2.1 ) Perform subretinal administration of LUXTURNA to each eye on separate days within a close interval, but no fewer than 6 days apart. ( 2.1 ) Recommend systemic oral corticosteroids equivalent to prednisone at 1 mg/kg/day (maximum of 40 mg/day) for a total of 7 days (starting 3 days before administration of LUXTURNA to each eye), and followed by a tapering dose during the next 10 days. ( 2.1 ) For subretinal injection only. 2.1 Dose The recommended dose of LUXTURNA for each eye is 1.5 x 10 11 vector genomes (vg), administered by subretinal injection in a total volume of 0.3 mL. Perform subretinal administration of LUXTURNA to each eye on separate days within a close interval, but no fewer than 6 days apart. Recommend systemic oral corticosteroids equivalent to prednisone at 1 mg/kg/day (maximum of 40 mg/day) for a total of 7 days (starting 3 days before administration of LUXTURNA to the first eye), and followed by tapering the dose during the following 10 days. The same corticosteroid dosing regimen applies for the administration of LUXTURNA to the second eye. If the corticosteroid taper following LUXTURNA administration to the first eye is not complete three days prior to the planned LUXTURNA administration to the second eye, then the corticosteroid regimen for the second eye replaces the taper for the first eye.

Endophthalmitis: Use proper aseptic injection technique and monitor for signs and symptoms of infection. ( 5.1 ) Permanent decline in visual acuity: Monitor for visual disturbances. ( 5.2 ) Retinal abnormalities: Monitor for macular abnormalities, retinal tears or breaks and chorioretinal atrophy. Do not inject in the immediate vicinity of the fovea. ( 5.3 ) Increased intraocular pressure: Monitor and manage intraocular pressure elevations. ( 5.4 ) Expansion of intraocular air bubbles: Air travel and/or scuba diving is not recommended until any intraocular air bubbles have been absorbed. ( 5.5 ) Cataract: Subretinal injection of LUXTURNA may result in cataract formation or increase in the rate of cataract progression. ( 5.6 ) 5.1 Endophthalmitis Endophthalmitis may occur following any intraocular surgical procedure or injection. Use proper aseptic injection technique when administering LUXTURNA. Following the injection, monitor patients to permit early treatment of any infection. Advise patients to report any signs or symptoms of infection or inflammation without delay. 5.2 Permanent Decline in Visual Acuity Permanent decline in visual acuity may occur following subretinal injection of LUXTURNA. Monitor patients for visual disturbances. 5.3 Retinal Abnormalities Retinal abnormalities may occur during or following the subretinal injection of LUXTURNA, including macular holes, foveal thinning, loss of foveal function, foveal dehiscence, chorioretinal atrophy, and retinal hemorrhage. Monitor and manage these retinal abnormalities appropriately.

The most common adverse reactions (incidence ≥ 5%) were conjunctival hyperemia, cataract, increased intraocular pressure, retinal tear, dellen (thinning of the corneal stroma), macular hole, subretinal deposits, eye inflammation, eye irritation, eye pain, and maculopathy (wrinkling on the surface of the macula). The most common adverse reactions (incidence ≥ 5%) in the clinical trials were conjunctival hyperemia, cataract, increased intraocular pressure, retinal tear, dellen (thinning of the corneal stroma), macular hole, subretinal deposits, eye inflammation, eye irritation, eye pain, and maculopathy (wrinkling on the surface of the macula). ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Spark Therapeutics, Inc. at 1-855-SPARKTX, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 trials of other products and may not reflect the rates observed in practice. The safety data described in this section reflect exposure to LUXTURNA in two clinical trials consisting of 41 subjects (81 eyes) with confirmed biallelic RPE65 mutation-associated retinal dystrophy. Forty of the 41 subjects received sequential subretinal injections of LUXTURNA to each eye. One subject received LUXTURNA in only one eye. Seventy-two of the 81 eyes were exposed to the recommended dose of LUXTURNA at 1.5 x 10 11 vg; 9 eyes were exposed to lower doses of LUXTURNA.

Pediatric use: Use in infants under 12 months of age is not recommended because of potential dilution or loss of LUXTURNA after administration due to the active retinal cell proliferation occurring in this age group. ( 8.4 ) 8.1 Pregnancy Risk Summary Adequate and well-controlled studies with LUXTURNA have not been conducted in pregnant women. Animal reproductive studies have not been conducted with LUXTURNA. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. 8.2 Lactation Risk Summary There is no information regarding the presence of LUXTURNA in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LUXTURNA and any potential adverse effects on the breastfed infant from LUXTURNA. 8.3 Females and Males of Reproductive Potential No nonclinical or clinical studies were performed to evaluate the effect of LUXTURNA on fertility. 8.4 Pediatric Use Treatment with LUXTURNA is not recommended for patients younger than 12 months of age, because the retinal cells are still undergoing cell proliferation, and LUXTURNA would potentially be diluted or lost during cell proliferation.

Metabolism

Biodistribution (within the body) and Vector Shedding (excretion/secretion) LUXTURNA vector DNA levels in various tissues and secretions were determined using a quantitative polymerase chain reaction (qPCR) assay. Nonclinical data Biodistribution of LUXTURNA was evaluated at three months following subretinal administration in non-human primates.

1. 1Intraocular Pressure Increased2214%
2. 2Retinal Degeneration159.9%
3. 3Eye Pain127.9%
4. 4Visual Impairment127.9%
5. 5Cataract85.3%
6. 6Chorioretinal Atrophy85.3%
7. 7Retinal Depigmentation85.3%
8. 8Retinal Tear85.3%
9. 9Ocular Hyperaemia74.6%
10. 10Vision Blurred74.6%
11. 11Drug Ineffective63.9%
12. 12Eye Inflammation63.9%
13. 13Ocular Hypertension63.9%
14. 14Blindness53.3%
15. 15Discomfort53.3%

The 6 most recently updated of 6 ClinicalTrials.gov registrations naming Voretigene Neparvovec as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study of Efficacy and Safety of Voretigene Neparvovec in Japanese Patients With Biallelic RPE65 Mutation-associated Retinal Dystrophy
  Completed · Phase 3 · Interventional · 4 enrolled · Novartis Pharmaceuticals
  NCT04516369updated 2026-06-04
• A Patient Registry Study for Patients Treated With Voretigene Neparvovec in US
  Completed · Observational · 87 enrolled · Spark Therapeutics, Inc.
  NCT03597399updated 2025-09-22
• Phase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 12 enrolled · Spark Therapeutics, Inc.
  NCT01208389updated 2025-04-29
• Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
  Active not recruiting · Phase 3 · Interventional · 31 enrolled · Spark Therapeutics, Inc.
  NCT00999609updated 2025-04-23
• Long-term Follow-up Study in Subjects Who Received Voretigene Neparvovec-rzyl (AAV2-hRPE65v2)
  Active not recruiting · Observational · 41 enrolled · Spark Therapeutics, Inc.
  NCT03602820updated 2025-04-18
• Safety Study in Subjects With Leber Congenital Amaurosis
  Completed · Phase 1 · Interventional · 12 enrolled · Spark Therapeutics, Inc.
  NCT00516477updated 2020-11-02

Frequently asked questions

How does Voretigene Neparvovec work?

LUXTURNA is designed to deliver a normal copy of the gene encoding the human retinoid isomerohydrolase RPE65 (RPE65) to cells of the retina in persons with reduced or absent levels of biologically active RPE65. The RPE65 is produced in the retinal pigment epithelial (RPE) cells and converts all- trans -retinol to 11- cis -retinol, which subsequently forms the chromophore, 11- cis -retinal, during the visual (retinoid) cycle.

What is Voretigene Neparvovec used for?

According to FDA labeling, Voretigene Neparvovec carries indications including: LUXTURNA (voretigene neparvovec-rzyl) is an adeno-associated virus vector-based gene therapy indicated for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. Patients must have viable retinal cells as determined by the treating physician(s).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Voretigene Neparvovec?

Voretigene Neparvovec is classified as Other ophthalmologicals, Adeno-associated Virus Vector, Gene Transduction or Replacement, Increased Retinal Pigment Epithelium Function.

What are the brand names for Voretigene Neparvovec?

Voretigene Neparvovec is marketed under brand names including Luxturna.

What are the contraindications for Voretigene Neparvovec?

Voretigene Neparvovec labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.