Luxturna’s Safety and Efficacy Profile Supported by Retrospective Data in Patients With RPE65-Associated Inherited Retinal Dystrophy

The commercially available gene therapy, developed by Spark Therapeutics, was evaluated in multiple studies presented at ARVO’s 2023 conference.

A retrospective study evaluating Spark Therapeutics’ voretigene neparvovec (Luxturna), a commercially available adeno-associated virus vector-based gene therapy intended to treat RPE65-mediated inherited retinal dystrophy (IRD), has produced safety and efficacy results consistent with previous studies.1 The findings were 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.

Among the 5 patients included in the retrospective study, treatment with the gene therapy was received in 10 eyes. Improvements in Goldmann visual field were reported in 7 of the 10 treated eyes. Furthermore, the average full-field light sensitivity threshold (FST; white) reached –8.97 db (±14.12) at the last follow-up, an improvement from the averages FST of –0.64 db (±7.29) recorded at baseline (trend towards a statistical significance, P = .09). On the other hand, the mean best-corrected visual acuity (BCVA) for the treated patients was similar at the last follow-up (1.17 LogMAR; ±0.38) to the mean BCVA at baseline (1.15 LogMAR; ±0.47; P = .93). All participants in the study reported subjective improvements in their vision following treatment with Luxturna.

In terms of safety, transient increases in intraocular pressure (IOP) were reported in 4 of the treated eyes. These adverse events (AEs) were treated with IOP lowering drops and oral acetazolamide; it was noted that this controlled the IOP. In addition, subtle intraocular inflammation in the anterior chamber was observed in 2 treated eyes; an extended topical steroid regimen was used to control these AEs. Additional AEs reported included cataract development in 3 eyes and areas of retinal atrophy in 8 eyes.

“In 6 eyes, retinal atrophy was subtle and inside the area of the raised bleb,” presenter Peter Kiraly, MD, PhD, a clinical research fellow at Oxford University Hospitals NHS Foundation Trust, and colleagues, wrote.1 “In a young patient with significant and stable FST improvements, atrophic changes also appear outside the bleb area in both eyes in a symmetric fashion.”

The ages of the patients included in the study ranged from 19 to 51 years (mean, 35.6). The group included 4 men and 1 woman. All 5 of the patients received treatment at the Oxford Eye Hospital. Kiraly and colleagues concluded that the safety and efficacy results of this study were consistent with results seen in previous studies of Luxturna. “The atrophic changes previously identified as a new adverse drug reaction have been observed in a majority of treated eyes in our cohort, but were not associated with loss of visual function,” Kiraly and colleagues added.1

A separate observational study, which was also presented at the ARVO 2023 Annual Conference, reported findings from 8 patients and 16 eyes treated with Luxturna in Belgium.2 This study reported statistically significant improvements in light sensitivity and in visual field using object III4. Similar to the study reported by Kiraly and colleagues, this study also found no statistically significant improvements in BCVA among the treated patients.

Luxturna was approved by the FDA in 2017 and in the European Union (EU) in 2018 and was the first gene therapy for a genetic disease to be approved in both the United States and the EU.3,4 In addition to the previously mentioned studies, Luxturna is also being evaluated for safety and efficacy in the ongoing PERCEIVE clinical trial, a postmarketing study which began in 2019.5 PERCEIVE will follow patients for up to 5 years after treatment with the gene therapy.

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1. Kiraly P, Cottriall C, Taylor LJ, et al. Functional outcomes and adverse effects of voretigene neparvovec for biallelic RPE65-mediated inherited retinal dystrophies in a cohort of patients from a single centre. Presented at: Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting. April 23-27, 2023; New Orleans, LA. Abstract #801 - C0402
2. Hertens L, Cauwenbergh CV, den Broeck FV, et al. Results of Belgian patients with RPE65-related inherited retinal dystrophy 6 months after treatment with voretigene neparvovec. Presented at: Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting. April 23-27, 2023; New Orleans, LA. Abstract #762 – C0363
3. FDA approves Spark Therapeutics’ LUXTURNA™ (voretigene neparvovec-rzyl), a one-time gene therapy for patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. News release. Spark Therapeutics. December 19, 2017. Accessed April 24, 2023.
4. European Commission approves Spark Therapeutics’ LUXTURNA® (voretigene neparvovec), a one-time gene therapy for inherited retinal disease caused by confirmed biallelic RPE65 mutations. News release. Spark Therapeutics. November 23, 2018. Accessed April 24, 2023.
5. Fischer MD, Maier R, Suhner A, et al. PERCEIVE study report: Real-world safety and effectiveness of voretigene neparvovec. Presented at: Association for Research in Vision and Ophthalmology (ARVO) 2022 Annual Meeting. May 1-4, 2022; Denver, CO.
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