Efficacy and Safety of Voretigene Neparvovec in RPE65-Retinopathy: Results of a Phase III Trial in Japan

Le résumé fourni par la source

Purpose We report the efficacy and safety of voretigene neparvovec (VN) as an adeno-associated viral vector-based gene therapy for Japanese patients with inherited retinal dystrophy (IRD) caused by biallelic pathogenic RPE65 variants ( RPE65 -retinopathy). Design Open-label, single arm, phase 3 clinical trial. Participants Four Japanese subjects were recruited following the criteria: (1) a clinical and molecular genetic diagnosis of RPE65 -retinopathy; (2) age four years or older; (3) a best-corrected visual acuity (BCVA) worse than 20/60 and/or a visual field (VF) less than 20 degrees by a III4e isopter or equivalent; and (4) sufficient viable retinal cells by optical coherence tomography and/or ophthalmoscopy. Methods All subjects received subretinal injections of VN (1.5 × 10 11 vg in 0.3 mL) after vitrectomy in both eyes. Main Outcome Measures The primary efficacy endpoint was a change from baseline in full-field light sensitivity threshold (FST) (white light, averaged over both eyes) at Days 30, 90, 180, and 270, and Year 1. The secondary efficacy endpoints included changes from baseline in VF testing by Goldmann kinetic perimetry (GP) and BCVA in the logarithm of the minimum angle of resolution (logMAR) unit. Safety was evaluated by adverse events (AEs), laboratory evaluations, and ophthalmological examinations. Results The mean baseline age of four subjects was 31.3 years (10, 17, 49, and 49 years). The homozygous pathogenic variants (c.1543C>T, p.Arg515Trp) were identified in three subjects. The mean (range) FST averaged over both eyes improved by -1.831 (-3.54 to -0.56) log 10 (cd.s/m 2 ) from baseline to Year 1 after treatment. The mean changes in VF as measured by (GP III4e) and logMAR BCVA, averaged across both eyes, were 427.8 (-11 to 1014) sum total degrees and -0.033 (-0.15 to 0.17) logMAR from baseline to Year 1, respectively. None of the AEs, including one serious AE (ovarian cyst torsion), were judged to be related to VN. Conclusions Overall, these data from a phase 3 trial showed improvements in FST and VF and well-tolerated safety profiles of VN for one year, with ongoing follow-up of up to five years in Japanese patients with RPE65 -retinopathy. These results support the further applicability of VN to the Japanese population.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.