The study found significant improvements in BCVA, in contrast to several other studies evaluating Luxturna.
Spark Therapeutics’ voretigene neparvovec (Luxturna), an FDA-approved adeno-associated virus vector-based gene therapy intended to treat RPE65-mediated inherited retinal dystrophy, demonstrated statistically significant improvements on several measures of visual outcome, including best-corrected visual acuity (BCVA), in a real-world setting, according to data presented at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, held April 23-27, in New Orleans, Louisiana.1
The study evaluated all consecutive patients (n = 12) who received bilateral treatment with Luxturna at a single site and who had at least 1 year of follow-up. The group had a mean age of 13.5 years (± 7.9). Among these patients, a significant improvement from baseline was observed in BCVA of -0.21 (± 0.14; P <.001) at 12 months posttreatment. On a full-field stimulus threshold (FST) test white light sensitivity thresholds showed a statistically significant improvement of –26.3 (± 10.7, P <.001). Furthermore, using chromatic pupillometry, the investigators observed significant improvements in maximum pupillary constriction in response to blue and white stimulus at 10 lux level (P <.05). Francesco Testa, of the Multidisciplinary Department of Medical, Surgical, and Dental Sciences, Universitadegli Studi della Campania Luigi Vanvitelli, who presented the data, and colleagues noted that they observed a significant relationship between improvements in sensitivity threshold and maximum pupillary constriction at 10 Lux with both white and blue light. The study also evaluated semi-automated kinetic visual field (SKVF); the investigators reported a significant enlargement of SKVF area using I4e (1921.7 ± 3247.3°2; P = .011) and III4e (2478 ± 3659.7°2; P <.001).
Testa and colleagues also pointed out that they observed bilateral retinal atrophy in 4 of the patients at 6 months of follow-up. They reported that this adverse event was not associated with worst outcomes on the efficacy measures, excepting SKVF using I4e stimulus size, in which patients with retinal atrophy showed significantly less improvement in their eyes (159.9 ± 1309.9°2) compared to the eyes of patients who were not experiencing retinal atrophy (2802.6 ± 3589.6°2; P = .033).
“Our findings showed significant improvements in visual outcomes, even in the case of retinal atrophy, after voretigene neparvovectreatment,” Testa and colleagues wrote.1 “Moreover, our results show, for the first time, the usefulness of chromatic pupillometry as an objective outcome measurement to evaluate treatment effects in patients with inherited retinal dystrophies.”
The improvements observed in BCVA in this study stand in contrast to results seen in several other studies of Luxturna which did not find significant improvement in BCVA, a common primary outcome in ophthalmologic clinical trials. For example, a retrospective study of 5 patients treated with Luxturna at the Oxford Eye Hospital, data from which were also presented at the ARVO 2023 annual meeting, found that 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), although improvements were observed in FST testing.2 The ages of the patients included in the study ranged from 19 to 51 years (mean, 35.6).
Likewise, data from a postmarketing observational study of 8 Belgian patients treated with Luxturna, also presented at the conference, showed no statistically significant improvement in BCVA, but improvements in FST testing.3 The ages of the patients included in the study ranged from 6 to 54 years (mean, 27.5).
Bart P. Leroy, MD, PhD, the head of the Department of Ophthalmology at the Center for Medical Genetics, Ghent University Hospital, who co-authored the poster on the study of the 8 Belgian patients, stated in an interview with CGTLive™ that the lack of improvement seen in BCVA in that study was expected based on results observed in the phase 3 clinical trial for Luxturna. Although, he clarified that the improvements observed in other efficacy measures have a meaningful impact on patients’ lives.
“The essence of the results of our study showed that the best corrected visual acuity indeed does not improve,” Leroy said during the interview. “We're talking about 19 eyes of 10 patients after 6 months—so this is early, and we have more data in the meantime—but this was when a certain cutoff was possible [because] we had to submit the abstract to ARVO. But I can definitely tell you what we've been obtaining since is showing that the results are very similar.”