Adeno-associated virus vector-based gene therapy via subretinal injection with voretigene neparvovec is considered medically necessary for individuals with vision loss due to biallelic RPE65 variant-associated retinal dystrophy if they meet all of the following criteria:
Are adults (age <65 years) or children (age ≥3 years) Documentation of the following: Genetic testing confirming presence of biallelic RPE65 pathogenic variant(s) or likely pathogenic variants (see Policy Guidelines for additional details) Single RPE65 pathogenic variant or likely pathogenic variant found in the homozygous state Two RPE65 pathogenic variants or likely pathogenic variants found in the trans configuration (compound heterozygous state) by segregation analysis Presence of viable retinal cells as determined by treating physicians as assessed by optical coherence tomography imaging and/or ophthalmoscopy: An area of retina within the posterior pole of >100 μm thickness shown on optical coherence tomography, OR
≥3 disc areas of retina without atrophy or pigmentary degeneration within the posterior pole, OR
Remaining visual field within 30° of fixation as measured by III4e isopter or equivalent.
Do not have any of the following:
Pregnancy in females.
Breastfeeding.
Use of retinoid compounds or precursors that could potentially interact with the biochemical activity of the RPE65 enzyme; individuals who discontinue use of these compounds for 18 months may become eligible.
Prior intraocular surgery within 6 months.
Preexisting eye conditions or complicating systemic diseases that would preclude the planned surgery or interfere with the interpretation of the study. Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (eg, radiotherapy of the orbit; leukemia with central nervous system/optic nerve involvement). Subjects with diabetes or sickle cell disease would be excluded if they had any manifestation of advanced retinopathy (eg, macular edema, proliferative changes). Also excluded would be subjects with immunodeficiency (acquired or congenital) because they could be susceptible to opportunistic infection (eg, cytomegalovirus retinitis).
Other applications of voretigene neparvovec are considered investigational.
