RPE65 mutation-associated RD is estimated to affect 1,000 to 3,000 people in the United States. It can be diagnosed as Leber congenital amaurosis type 2, early onset severe retinal dystrophy, severe early childhood-onset retinal dystrophy, and retinitis pigmentosa type 20 among others.
Diagnostic confirmation through genetic testing is mandatory for identifying patients who would be eligible for voretigene. Spark Therapeutics is offering access to the evaluation.
“RPE65 mutation-associated RD presents with a spectrum of symptoms, which makes it difficult for anyone to establish the diagnosis clinically,” said Dr. Falabella.
“Ophthalmologists who suspect a patient has RD-affecting rods should refer that individual for genetic testing,” Dr. Falabella added. “Night blindness, which may manifest as light-seeking behavior in very young patients, has been consistently linked to RPE65-mutation associated RD.”
Entry into the premarketing clinical trial was limited to children aged ≥3 years as a practical consideration so enrolled participants had the ability to perform the study assessments. However, the gene therapy was approved for treatment of children aged ≥1 year, recognizing that RPE65-mutation associated RD is a progressive degenerative disease and that efficacy of the gene therapy depends on the presence of viable cells.
“It is important to treat affected patients as early as possible, given the progressive nature of the disease, although age was not a clear predictor of response in the clinical trial and even the oldest patient in the study showed significant improvement after intervention,” Dr. Falabella said. “Our youngest participant was 4 years old, and so we will see if there is any trend after younger patients are treated.”
Dr. Falabella added that for all eligible patients, the potential treatment benefit has to be balanced against the potential risks of the delivery procedure. The 1-year age limit considered that retinal cells are still undergoing cell proliferation during the first year of life, which would potentially cause dilution or loss of voretigene.