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 biallelicRPE65mutation-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 withRPE65mutation-associated IRD and sufficient viable retinal cells.