Voretigene Neparvovec: A Review in RPE65 Mutation-Associated Inherited Retinal Dystrophy.

Voretigene neparvovec (Luxturna®), a recombinant adeno-associated virus vector-based gene therapy, delivers a functioning copy of the human retinal pigment epithelium-specific 65 kDa (RPE65) gene into retinal cells of patients with reduced or absent levels of RPE65 protein, providing the potential to restore the visual cycle. A single-dose subretinal injection of voretigene neparvovec administered in each eye is approved in several countries worldwide for the treatment of vision loss in adult and paediatric patients with confirmed biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD) and with sufficient viable retinal cells. In the pivotal phase III trial, significant improvements from baseline were seen in the mean bilateral multi-luminance mobility test scores in the voretigene neparvovec group compared with the control group at 1 year. The beneficial effects of voretigene neparvovec treatment were maintained after up to 4 years of follow-up (with follow-up continuing for 15 years). Control recipients were eligible to receive voretigene neparvovec at 1 year, and showed improvements at subsequent follow-ups (≤ 3 years post injection) consistent with those in patients who received voretigene neparvovec at baseline. Most adverse reactions in voretigene neparvovec recipients were transient, asymptomatic and non-serious, and resolved without sequelae (may have been related to voretigene neparvovec, the subretinal injection procedure, concomitant corticosteroid use or a combination thereof). Retinal detachment occurred in one patient at year 4. Although ongoing additional long-term efficacy and safety data are required, voretigene neparvovec is an important novel gene therapy for patients with RPE65 mutation-associated IRD and sufficient viable retinal cells.