AAV5-RPGR gene therapy for X-linked retinitis pigmentosa effective at 12 months
At 12 months, data from the phase 1/2 study of AAV5-RPGR gene therapy for RPGR-associated X-linked retinitis pigmentosa showed significant improvement in retinal sensitivity and functional mobility with the low and intermediate doses.
“Given the robust safety and efficacy signals observed, these doses are being further explored with analyses at additional data time points in the ongoing randomized controlled dose-expansion phase of the study,” Michel Michaelides, MD, said at the virtual American Academy of Ophthalmology annual meeting.
In the low- and intermediate-dose cohorts, significant improvement in retinal sensitivity was observed at 3 months and 9 months and was maintained at 1 year, both in terms of mean retinal sensitivity and volumetric analysis of the 30° hill of vision on the Octopus 900 perimeter (Haag-Streit).
“Looking at the point-by-point response, we could observe a significant difference between treated and untreated eyes in the number of points in the grid. Mesopic microperimetry data in the intermediate-dose cohort at month 12 showed a significant decrease of retinal sensitivity over time in the untreated eyes, while three out of four subjects showed improvement or stability in the treated eye,” Michaelides said.
Patients were also tested on their ability to walk through a maze at different illumination levels to determine the impact of the improvement in retinal sensitivity on real-world vision-guided activities of daily living.
For one patient, it took about 1 minute to complete the maze at baseline; he bumped into a barrier and groped along trying to locate the way out. At 9 months, the same patient was able to navigate the maze using the treated eye in 16 seconds and made no errors.
“We saw a tremendous improvement in function. In low light conditions, there was a statistically significant improvement in vision-guided mobility in the low- and intermediate-dose cohorts between the treated and untreated eye,” Michaelides said.
Safety data suggest that AAV5-RPGR (MeiraGTx/Janssen Pharmaceutical) is generally safe and well tolerated. Adverse events were mostly related to the surgical delivery procedure, were transient and resolved with intervention. No dose-limiting events were reported. Inflammation was observed in two out of three patients in the high-dose cohort and were treated with extension of steroid cover.
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Michaelides M, et al. Phase 1/2 trial of AAV5-RPGR gene therapy for RPGR-associated X-linked retinitis pigmentosa (XLRP): 12-month results. Presented at: American Academy of Ophthalmology annual meeting; Nov. 13-15, 2020 (virtual meeting).
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