Bart P. Leroy, MD, PhD, on Aligning IRD Gene Therapy Outcome Measures With Activities of Daily Living

“...Although we did have a lot of success in getting Luxturna to market, other innovative therapies that are being developed and are very much under study currently have failed sometimes to reach the stage where they get market authorization—and this is often not because they don't work.”

Currently, the FDA typically requires investigational treatments that use best-corrected visual acuity (BCVA) as an outcome measure in clinical trials to demonstrate an improvement of at least 3 lines in BCVA to qualify for commercial approval. Similarly, the European Medicines Agency typically requires such treatments to demonstrate an improvement of 2 lines on a LogMAR scale.

Bart P. Leroy, MD, PhD, the head of the Department of Ophthalmology at the Center for Medical Genetics at Ghent University Hospital, coauthored a poster entitled, “Results of Belgian patients with RPE65-related inherited retinal dystrophy 6 months after treatment with voretigene neparvovec,” which was presented at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, held April 23-27, 2023, in New Orleans, Louisiana. The poster described results from 8 Belgian patients who were treated with 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. The results showed that the patients did not obtain a statistically significant improvement in BCVA, but they did experience clinically meaningful improvements in light sensitivity.

In an interview with CGTLive™, Leroy discussed the need to reevaluate the outcome measures used by regulatory agencies that determine whether gene therapy products for conditions like IRD should be given marketing authorization. He pointed out that even when improvements in BCVA are not possible, a gene therapy slowing or halting degeneration of vision is a meaningful change for patients. He also stressed the need to develop new outcome measures that correlate the effects of investigational gene therapies with improvements in activities of daily living.

REFERENCES
1. 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