PERCEIVE study report: Real-world safety and effectiveness of voretigene neparvovec

Abstract

Purpose : Voretigene neparvovec (VN) is the first approved ocular gene therapy for patients with RPE65-mediated inherited retinal dystrophy and sufficient viable retinal cells. PERCEIVE is a post-authorization safety study assessing long-term safety and effectiveness of VN in a real-world setting.

Methods : PERCEIVE is an ongoing (2019–2029), prospective, longitudinal, multicenter (ex-US), registry-based observational study. All VN-treated patients, including those treated prior to enrollment, were considered eligible. Patients are treated according to local prescribing information and followed-up as per the routine clinical practice for 5 years. The primary objective is to collect adverse events (AEs), including AEs of special interest (AESIs). Secondary objectives include assessment of pregnancy outcomes and visual function over time.

Results : Up to August 2021, 106 patients were enrolled, of whom 103 received VN (mean age [SD]: 19.5 [10.85] years; females: 52 [50.5%]). Mean (SD) duration of follow-up was 0.8 (0.64) years (maximum: 2.3 years). A total of 35 patients (34.0%) reported ≥1 ocular AEs including those with ocular AESIs (number of patients [n] = 17 [16.5%]). Events of chorioretinal atrophic changes (at injection site and/or elsewhere, n = 13) were the most common ocular AEs. Ocular AESIs included foveal degeneration (n = 4), vitritis (n = 4), eye inflammation (n = 3), retinal tear (n = 2) and increased intraocular pressure (IOP; n = 5). Two patients had ocular serious AEs (SAEs: eye inflammation, n = 1; increased IOP, n = 1). Non-ocular AEs occurred in 8 patients; most frequent AE was headache (n = 4). One patient, with no previous history, reported 3 events of psychiatric disorder (non-ocular SAEs). Visual function improved in terms of full-field light sensitivity threshold, and best-corrected visual acuity (LogMAR) at Year 2 with a mean (SD) change from baseline of −13.67 (22.62) decibels and −0.03 (0.55), respectively (Table).

Conclusions : Overall, the safety and effectiveness of VN observed in the PERCEIVE study, with up to 2-years data, are consistent with the findings of VN clinical trials. Chorioretinal atrophy has been identified as a new adverse drug reaction, which so far has not been associated with loss of visual function. These events and overall longer-term safety will be further characterized in the ongoing study.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Table. Effectiveness of VN following up to 2 years of administration