The new positive data on the AAV based gene therapy builds upon real-world data presented at ARVO’s conference in 2022.
Spark Therapeutics’ voretigene neparvovec (Luxturna), a commercially available adeno-associated virus vector-based gene therapy intended to treat inherited retinal dystrophy (IRD) related to mutations in the RPE65 gene, has demonstrated improvements in 8 Belgian patients, according to data presented in a poster at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, held April 23-27, in New Orleans, Louisiana.1
Among the 8 patients and 16 eyes in the observational study, treatment was received in a total of 15 eyes. Significant improvements in light sensitivity were reported at 6 months posttreatment for red light (µ = –1.70; s = 2.30 log cd/m2; P = .014), blue light (µ = –2.49; s = 2.06 log cd/m2; P = .007), and white light (µ = –2.63; s = 3.09 log cd/m2; P = .021). Beyond the improvements in light sensitivity, statistically significant improvement was also observed in visual field using object III4 (µ = 305.79; s = 411.57 TSD; P = .029). There were no statistically significant improvements in best-corrected visual acuity (BCVA) nor any other statistically significant changes in the patients’ vision reported.
Leen Hertens, Msc, a clinical research coordinator at Ghent University Hospital, who presented the poster, and colleagues had hypothesized based on previous studies that improvements in light sensitivity and visual field would be observed in the patients while BCVA would not be impacted by treatment with the gene therapy. They noted that the results of the study were in line with this hypothesis but pointed out that because of the small samples sizes, there may have been other changes that were not detected. The prospective, longitudinal study required included patients to have the presence of photoreceptor cells detectable on optical coherence tomography images, a molecularly confirmed diagnosis of RPE65-associated IRD, and vision capable of light perception or better. The findings at 6 months posttreatment were compared to the patients’ measurements at screening.
This positive data builds upon positive real-world data that was presented at the 2022 ARVO Annual Meeting.2 PERCEIVE, a postmarketing clinical trial launched in 2019 that will follow patients for up to 5 years, had treated 103 patients as of the August 2021 data cutoff. The efficacy results included a mean change from baseline in BCVA of –0.03 at 2 years posttreatment and a mean change from baseline in full-field light sensitivity threshold of –13.67 decibels at 2 years posttreatment. In terms of safety, 1 or more ocular adverse events (AEs) were reported in 35% of the patients. The most common AE was chorioretinal atrophic changes at the injection site or elsewhere; there were 13 cases of this AE.
Luxturna was originally approved by the FDA in December 2017 for the treatment of patients with mutations in both copies of RPE65 who have sufficient viable retinal cells for the treatment as assessed by their physician.3 It was the first gene therapy approved by the FDA for the treatment of a genetic disease. About 1 year later, in November 2018, Spark Therapeutics announced that Luxturna had received marketing authorization from the European Commission (EC) in all member states of the European Union, Iceland, Liechtenstein, and Norway.4 This decision made it the first gene therapy for a genetic disease to be approved by both the FDA and the EC.
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