Gene therapy developments

Nine months of follow-up in a phase I/II clinical trial of AAV-RPGR gene therapy for RPGR-associated X-linked retinitis pigmentosa show encouraging results, reported Michel Michaelides MD, at the EURETINA 2020 Virtual meeting. He presented findings from the dose-escalation phase of the study that enrolled adults and included low-, intermediate- and high-dose cohorts. The safety review showed that, so far, the treatment was safe and well-tolerated with no dose-limiting adverse events, with the majority of recorded adverse events being anticipated from the surgical procedure. Efficacy assessments in the low- and intermediate-dose cohorts showed patients achieved significant improvement in vision-guided mobility at low light levels and clinically meaningful improvements in retinal sensitivity across multiple metrics and modalities. “Given the robust safety and efficacy signals observed, the low and intermediate doses are being further explored with analyses at additional data time points in an ongoing, randomised, controlled dose expansion phase of the study,” said Dr Michaelides, Professor of Ophthalmology, University College London Institute of Ophthalmology and Moorfields Eye Hospital, London, UK. The dose-escalation phase of the phase I/II trial is the first of three parts. The trial is being undertaken at five sites in the United States and United Kingdom. The dose-escalation study enrolled three patients each into the low- and high-dose cohorts and four into the intermediate-dose cohort. All patients received a single injection into the worse seeing eye. Mean age of the 10 patients was 24 years and mean baseline BCVA was 69 ETDRS letters. The efficacy endpoints included measurements of retinal sensitivity with full field static perimetry that showed statistically significant differences between the treated and untreated eyes among patients in the low- and intermediate-dose cohorts in analyses of mean retinal sensitivity, the central 30º hill of vision, and also using a point-wise analysis. Dr Michaelides reported that a significant difference in retinal sensitivity between the treated and untreated eyes was observed by three months, which was the timing of the first post-treatment measurement. A strong indication of clinical activity in the low- and intermediate-dose cohorts was also evident in analyses of mesopic microperimetry, he said. Functional vision was assessed using data from mobility maze testing. The results showed time taken to navigate the maze was significantly improved from baseline to nine months at 1 lux, which was the lowest light level used for testing, and also at 4 lux.