Voretigene neparvovec in patients with RPE65 mutation-associated inherited retinal dystrophy: Baseline characteristics from the real-world, prospective, observational PERCEIVE study

ABSTRACT

Purpose: Voretigene neparvovec (VN) is the first ocular gene therapy approved in multiple countries including the USA and Europe for treating patients (pts) with visual impairment due to confirmed biallelic RPE65 mutation-associated inherited retinal dystrophy having sufficient viable retinal cells. PERCEIVE, a registry-based post-authorization safety study, is designed to assess long-term safety of VN in a real-world (RW) setting. Here, baseline characteristics of participating pts treated with VN up to August 2020 are reported. Methods: PERCEIVE is an ongoing, prospective, longitudinal, multicenter (ex-US), observational, safety study, which commenced December 2019 with the aim to enroll a minimum of 40 pts. All VN-treated pts are encouraged to participate in the study to maximize data collection, including those treated prior to study inception. After receiving VN as per local prescribing information, pts are followed-up as per the routine medical care for 5 years. The objectives are to characterize the long-term safety profile of VN via systematic collection of adverse event data, to follow pregnancy outcomes and assess visual function over time. Results: Until data cut-off (Aug 2020), of the 15 pts enrolled, 10 pts (16 eyes) have received VN (6 bilateral;4 unilateral). All treated pts are from Europe (Germany 6;France 3;Austria 1). At the time of enrollment, the mean (standard deviation [SD]) age was 27.6 (9.81) years with a range of 15-51 years (1 adolescent;9 adults). The majority of treated pts are female (n=7;70%). For the treated eyes (n=16), baseline mean (SD) visual acuity was 0.96 (0.37) logMAR (n=14;range 0.5-1.6 logMAR) and full-field stimulus threshold (white light) was -4.32 (9.40) dB (n=15;range -34.9 to 3.2 dB). Optical coherence tomography (OCT) revealed a mean foveal thickness of 150.5 (41.07) μm (n=15;range 76- 216 μm). Central OCT showed that 11 eyes had an outer nuclear layer with a thickness range of 36-74 μm (n=9), while it was absent in 4 eyes. The ellipsoid zone line was disrupted in 9 eyes and was undetected in 6. Conclusions: While enrollment and in person follow-up of VN-treated pts has been impacted due to COVID-19, PERCEIVE has started to provide valuable information on baseline characteristics of this vision-impaired population, and effect of VN therapy in a RW setting.