Journal article
Durability of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease: Phase 3 Results at 3 and 4 Years
Ophthalmology (Rochester, Minn.), Vol.128(10), pp.1460-1468
03/30/2021
DOI: 10.1016/j.ophtha.2021.03.031
PMID: 33798654
Abstract
To determine whether functional vision and visual function improvements after voretigene neparvovec (VN; Luxturna [Spark Therapeutics, Inc]) administration in patients with biallelic RPE65 mutation-associated inherited retinal disease are maintained at 3 to 4 years and to review safety outcomes.
Open-label, randomized, controlled phase 3 trial.
Thirty-one individuals were enrolled and randomized 2:1 to intervention (n = 21) or control (n = 10). One participant from each group withdrew before, or at, randomization.
Patients in the original intervention (OI) group received bilateral subretinal VN injections. Delayed intervention (DI) patients served as control participants for 1 year then received VN.
Change from injection baseline in bilateral performance on the multiluminance mobility test (MLMT), a measure of ambulatory navigation, and change from injection baseline in full-field light sensitivity threshold white light, visual field (VF), and visual acuity (VA).
Mean bilateral MLMT change scores at year 4 for OI patients and year 3 for DI patients were 1.7 and 2.4, respectively, with 71% of patients with a year 3 visit able to pass MLMT at the lowest light level. Mean change in full-field light sensitivity threshold white light, averaged over both eyes at year 4 for OI patients and year 3 for DI patients, was -1.90 log
(cd.s/m
) and -2.91 log
(cd.s/m
), respectively. Mean change in Goldmann kinetic VF III4e sum total degrees, averaged across both eyes, was 197.7 at year 4 for OI patients and 157.9 at year 3 for DI patients. Mean change in VA (Holladay scale), averaged across both eyes, was -0.003 logarithm of the minimum angle of resolution (logMAR) at year 4 for OI patients and -0.06 logMAR at year 3 for DI patients. One OI patient experienced retinal detachment at approximately year 4 that impacted VA for the OI group. No product-related serious adverse events (AEs) occurred, nor did any deleterious immune responses.
Improvements in ambulatory navigation, light sensitivity, and VF were consistent in both intervention groups. Overall, improvements were maintained up to 3 to 4 years, with ongoing observation. The safety profile of VN was consistent with vitrectomy and the subretinal injection procedure and was similar between intervention groups, with no product-related serious AEs reported.
Details
- Title: Subtitle
- Durability of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease: Phase 3 Results at 3 and 4 Years
- Creators
- Albert M Maguire - Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Cellular and Molecular Therapeutics, Inc., Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Electronic address: amaguire@pennmedicine.upenn.eduStephen Russell - Department of Ophthalmology and Visual Sciences, University of Iowa Institute for Vision Research, University of Iowa, Iowa City, IowaDaniel C Chung - Spark Therapeutics, Inc., Philadelphia, PennsylvaniaZi-Fan Yu - SparingVision, Philadelphia, PennsylvaniaAmy Tillman - SparingVision, Philadelphia, PennsylvaniaArlene V Drack - Department of Ophthalmology and Visual Sciences, University of Iowa Institute for Vision Research, University of Iowa, Iowa City, IowaFrancesca Simonelli - Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania "Luigi Vanvitelli", Naples, ItalyBart P Leroy - Division of Ophthalmology and Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Ophthalmology and Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, BelgiumKathleen Z Reape - Spark Therapeutics, Inc., Philadelphia, PennsylvaniaKatherine A High - Spark Therapeutics, Inc., Philadelphia, PennsylvaniaJean Bennett - Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Cellular and Molecular Therapeutics, Inc., Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
- Resource Type
- Journal article
- Publication Details
- Ophthalmology (Rochester, Minn.), Vol.128(10), pp.1460-1468
- DOI
- 10.1016/j.ophtha.2021.03.031
- PMID
- 33798654
- ISSN
- 0161-6420
- eISSN
- 1549-4713
- Language
- English
- Electronic publication date
- 03/30/2021
- Academic Unit
- Stead Family Department of Pediatrics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984101612902771
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