Significant improvement observed in X-linked retinitis pigmentosa treated with AAV-RPGR
Nine-month data from a phase 1/2 clinical trial of AAV-RPGR gene therapy for X-linked retinitis pigmentosa showed clinically meaningful improvement in retinal sensitivity and vision-guided mobility.
“The most significant finding is that treatment can result in an improvement in vision in a way that went beyond our expectations,” Michel Michaelides, MD, said at the virtual Euretina congress.
Disease-causing variants in the RPGR gene account for more than 70% of cases of X-linked retinitis pigmentosa and up to 20% of all cases of retinitis pigmentosa. AAV-RPGR (MeiraGTx/Janssen Pharmaceutical) is designed to deliver functional copies of the RPGR gene to the subretinal space. In the dose-escalation phase of the ongoing trial, patients were treated with a low, intermediate or high dose in the worse eye, and the contralateral eye was used as a control.
Retinal sensitivity was assessed using Octopus 900 full-field static perimetry (Haag-Streit) and Maia microperimetry (CenterVue). At 9 months, a statistically significant improvement was observed in both the low- and intermediate-dose cohorts.
“The difference between treated and untreated eyes was statistically significant. While treated eyes showed improvement over time, from baseline to 6 months and from 6 to 9 months, untreated eyes had a steady decline,” Michaelides said.
For functional assessment, patients completed a vision-guided mobility maze to assess their ability to navigate through various configurations and light levels.
“We have been able to observe significant improvement, especially in the intermediate group and at the lower light levels. There was a significant difference between treated and untreated eyes,” Michaelides said.
The treatment was well tolerated. Adverse events were mostly related to the surgery, and there were no dose-limiting events.
“The low and intermediate doses have gone forward into the randomized controlled dose-expansion phase of the study,” Michaelides said.
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Michaelides M. FP-459972 - Phase 1/2 clinical trial of AAV-RPGR gene therapy for RPGR-associated X-Linked retinitis pigmentosa: 9-month results. Presented at: Euretina congress; Oct. 2-4, 2020 (virtual meeting).
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