Get to know RPE65

The RPE65 gene is essential to the visual cycle1

The RPE65 gene encodes the RPE65 protein. RPE65 is necessary for vitamin A metabolism in photoreceptor cells. The RPE65 protein is located in the retinal pigment epithelial (RPE) cells and converts all-trans-retinol to 11-cis-retinol, which subsequently forms 11-cis-retinal during the visual cycle. The visual cycle is critical in the biological conversion of light into electrical signals.2,3

Mutations in the RPE65 gene lead to vision loss due to loss of function (or death) of RPE cells and eventual degeneration of photoreceptors.3,4

Illustration of the visual cycle being restored

It’s time for a genetic diagnosis—and it starts with you

Clinical diagnoses based on phenotype, such as retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), are not definitive. These diagnoses describe variation in onset, degree of severity, and progression of disease.3,5-8

Symptoms may differ depending on when a patient presents with biallelic RPE65 mutation-associated retinal dystrophy. The hallmark of this disease is rod dysfunction that leads to night blindness, or the inability to see in dim lighting, in almost all patients. Take a look below for some symptoms commonly associated with biallelic RPE65 gene mutations.4,8,9

Woman smiling Photographs are not of actual patients.

Adolescents & Adults:

  • Nyctalopia9
  • Prolonged dark adaptation10
  • Peripheral visual field loss9
  • Severely reduced/undetectable ERG10
  • Severe loss of visual acuity (≥20/200)10
Young boy smiling

Young Children:*

  • Nyctalopia8
  • Nystagmus2
  • Prolonged dark adaptation11
  • Reduced ERG2
  • Failure to fix and follow2
  • Sensitivity to light8
  • Mild loss of visual acuity (<20/200)8

*LUXTURNA is not recommended for children under 12 months of age.

Graphic icon of test tubes

These symptoms are not exclusive to RPE65
mutation-associated retinal dystrophy, which is why
genotyping is the only way to reach a definitive diagnosis3,5-8

INDICATION

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 physicians.

IMPORTANT SAFETY INFORMATION FOR LUXTURNA

Warnings and Precautions

  • Endophthalmitis may occur following any intraocular surgical procedure or injection. Use proper aseptic injection technique when administering

INDICATION

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 physicians.

IMPORTANT SAFETY INFORMATION FOR LUXTURNA

Warnings and Precautions

  • Endophthalmitis may occur following any intraocular surgical procedure or injection. Use proper aseptic injection technique when administering LUXTURNA, and monitor for and advise patients to report any signs or symptoms of infection or inflammation to permit early treatment of any infection.

  • Permanent decline in visual acuity may occur following subretinal injection of LUXTURNA. Monitor patients for visual disturbances.

  • Retinal abnormalities may occur during or following the subretinal injection of LUXTURNA, including macular holes, foveal thinning, loss of foveal function, foveal dehiscence, and retinal hemorrhage. Monitor and manage these retinal abnormalities appropriately. Do not administer LUXTURNA in the immediate vicinity of the fovea. Retinal abnormalities may occur during or following vitrectomy, including retinal tears, epiretinal membrane, or retinal detachment. Monitor patients during and following the injection to permit early treatment of these retinal abnormalities. Advise patients to report any signs or symptoms of retinal tears and/or detachment without delay.

  • Increased intraocular pressure may occur after subretinal injection of LUXTURNA. Monitor and manage intraocular pressure appropriately.

  • Expansion of intraocular air bubbles Instruct patients to avoid air travel, travel to high elevations or scuba diving until the air bubble formed following administration of LUXTURNA has completely dissipated from the eye. It may take one week or more following injection for the air bubble to dissipate. A change in altitude while the air bubble is still present can result in irreversible vision loss. Verify the dissipation of the air bubble through ophthalmic examination.

  • Cataract Subretinal injection of LUXTURNA, especially vitrectomy surgery, is associated with an increased incidence of cataract development and/or progression.

Adverse Reactions

  • In clinical studies, ocular adverse reactions occurred in 66% of study participants (57% of injected eyes), and may have been related to LUXTURNA, the subretinal injection procedure, the concomitant use of corticosteroids, or a combination of these procedures and products.

  • The most common adverse reactions (incidence ≥5% of study participants) were conjunctival hyperemia (22%), cataract (20%), increased intraocular pressure (15%), retinal tear (10%), dellen (thinning of the corneal stroma) (7%), macular hole (7%), subretinal deposits (7%), eye inflammation (5%), eye irritation (5%), eye pain (5%), and maculopathy (wrinkling on the surface of the macula) (5%).

Immunogenicity

Immune reactions and extra-ocular exposure to LUXTURNA in clinical studies were mild. No clinically significant cytotoxic T-cell response to either AAV2 or RPE65 has been observed.

In clinical studies, the interval between the subretinal injections into the two eyes ranged from 7 to 14 days and 1.7 to 4.6 years. Study participants received systemic corticosteroids before and after subretinal injection of LUXTURNA to each eye, which may have decreased the potential immune reaction to either AAV2 or RPE65.

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 the cell proliferation. The safety and efficacy of LUXTURNA have been established in pediatric patients. There were no significant differences in safety between the different age subgroups.

Please see US Full Prescribing Information for LUXTURNA.

References:

1. Cai X, Conley SM, Naash MI. RPE65: Role in the visual cycle, human retinal disease, and gene therapy. Ophthalmic Genet. 2009;30(2):57-62. 2. Cideciyan AV. Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog Retin Eye Res. 2010;29(5):398-427. 3. LUXTURNA [package insert]. Philadelphia, PA: Spark Therapeutics, Inc; 2017. 4. Russell S, Bennett J, Wellman JA, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017;390(10097):849-860. 5. Lee K, Garg S. Navigating the current landscape of clinical genetic testing for inherited retinal dystrophies. Genet Med. 2015;17(4):245-252. 6. Nash BM, Wright DC, Grigg JR, Bennetts B, Jamieson RV. Retinal dystrophies, genomic applications in diagnosis and prospects for therapy. Transl Pediatr. 2015;4(2):139-163. 7. Data on File. CSR RPE65 NHx:16,61. Jan 11, 2017. Spark Therapeutics, Inc. Philadelphia, PA. 8. Chacon-Camacho OF, Zenteno JC. Review and update on the molecular basis of Leber congenital amaurosis. World J Clin Cases. 2015;3(2):112-124. 9. Genetics Home Reference, US National Library of Medicine, National Institutes of Health. Retinitis pigmentosa. https://ghr.nlm.nih.gov/condition/retinitis-pigmentosa. Accessed May 18, 2017. 10. Fahim AT, Daiger SP, Weleber RG. Nonsyndromic Retinitis Pigmentosa Overview. Gene Reviews [serial online]. August 4, 2000. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1417/. Accessed May 18, 2017. 11. Felius J, Thompson DA, Khan NW, et al. Clinical course and visual function in a family with mutations in the RPE65 gene. Arch Ophthalmol. 2002;120(1):55-61.