Author: M. Dominik Fischer
Co-authors: Rainer Maier, Andrea Suhner, Daniel Stiehl, Christina Fasser, Bart P. Leroy
Abstract
Purpose: Inherited retinal dystrophies (IRDs) are rare heterogeneous disorders caused by mutation in any of >250 genes. Biallelic RPE65 mutation-associated IRDs result in progressive vision loss, ultimately leading to complete blindness. Voretigene neparvovec (VN) is a recombinantadeno-associated virus type 2 vector containing human RPE65 complementary DNA, that expresses the RPE65 protein. It is the first ocular gene therapy available for patients with
RPE65-associated IRDs with sufficient viable retinal cells. PERCEIVE is a post-authorization study evaluating the long-term safety and effectiveness of VN in a real-world setting. Findings from the study until August 2021 are presented here.
Setting: PERCEIVE is an ongoing, prospective, longitudinal, multicenter (ex-US), registry-based, observational study. The study was initiated in December 2019 with a 5-year enrollment period and is planned for completion by December 2029. Patients are treated as per routine clinical practice.
Methods: Patients are considered eligible if they have or are planning to receive VN in at least one eye, including those treated prior to study enrollment, and have not participated, or are currently participating, in any interventional trial with VN. VN is administered according to local prescribing information and patients are followed-up for 5 years as per routine clinical practice. The primary objective of this study is to collect information on adverse events (AEs) of special interest (AESIs), and any other AEs. Secondary objectives included assessment of pregnancy outcomes and visual function (e.g., as measured by full-field light sensitivity threshold [FST; white light], best-corrected visual acuity [BCVA], and visual field) over time. The full analysis set, including all enrolled patients who have received VN in at least one eye, was used for the analysis.
Results: At the 2-year cut-off, 106 patients were enrolled, of whom 103 had received VN. The mean age (standard deviation [SD]) of patients was 19.5 (10.85) years and 52 (50.5%) were women. The mean (SD) length of follow-up was 0.8 (0.64) years (maximum: 2.3 years). At least 1 ocular AE was reported in 35 patients (34.0%). The most common ocular AE was chorioretinal atrophy (at the injection site and/or elsewhere, number of patients [n]=13). Ocular AESIs occurred in
17 (16.5%) patients, which included foveal degeneration (n=4), vitritis (n=4), eye inflammation (n=3), retinal tear (n=2), and increased intraocular pressure (IOP; n=5). Ocular serious AEs (SAEs) were reported in 2 patients (eye inflammation, n=1; increased IOP, n=1). Eight patients had non-ocular AEs; the most frequent was headache (n=4). Three events of psychiatric disorder (SAE) occurred in 1 patient with no previous history of such events. Visual function improved at Years1 and 2 with a mean (SD) change from baseline of −15.84 (14.10; n=10) and −13.67 (22.62; n=13) decibels in FST, and −0.07 (0.18; n=19) and −0.03 (0.55; n=24) in BCVA (LogMAR), respectively.
Conclusions: Based on this Year 2 interim analysis, the PERCEIVE study demonstrates the safety and effectiveness of VN, which is consistent with those observed in the pivotal VN clinical trials. Chorioretinal atrophy has been identified as a new adverse drug reaction from post-marketing experience. In patients in which chorioretinal atrophy was reported as an AE following VN administration, visual function has not been affected thus far. As the study progresses, such AEs and the long-term safety profile of VN will be better characterized. Furthermore, PERCEIVE will provide real-world evidence on the long-term durability of vision improvements observed with VN therapy.
