Voretigene Neparvovec: An Emerging Gene Therapy for the Treatment of Inherited Blindness

Inherited retinal dystrophies (IRDs) are a major cause of early-onset blindness. Biallelic RPE65-mediated IRD, the most severe form of IRD, occurs when there are mutations in both alleles of the RPE65 gene in retinal pigment epithelium (RPE) cells. Voretigene neparvovec, developed by Spark Therapeutics, Inc., Pennsylvania, US, is a gene therapy designed to deliver a normal copy of the RPE65 gene to the RPE cells that are lacking a normally functioning RPE65 gene. This is the first gene therapy that has completed a phase III clinical trial — a randomized, open-label, controlled trial assessing the safety and efficacy of voretigene neparvovec for the treatment of biallelic RPE65-mediated IRD. In the phase III trial, patients treated with voretigene neparvovec showed significant improvement in navigational ability in dimly light conditions, compared with the control group, at one year. This treatment was associated with mild to moderate ocular adverse events; one patient experienced a loss of visual acuity in the first assigned eye. Improvement in visual function appears to remain durable for up to three years based on current data. Longer-term safety and efficacy data for voretigene neparvovec are needed to confirm its duration of effect, its impact on retinal degeneration, and the impact on the quality of life of participants treated with this therapy. The US FDA approved voretigene neparvovec (voretigene neparvovec-rzyl as per the FDA label) on December 19, 2017 under the trade name Luxturna. The drug is also currently under review by the European Medicines Agency, with a decision expected in the latter half of 2018. In the US, the price of voretigene neparvovev-rzyl has been set to US$425,000 per eye (US$850,000 for bilateral disease); this is a one-time treatment.