AAV8-RGPR Demonstrates Safety, Efficacy in X-Linked Retinitis Pigmentosa


Results of a phase 1 study examining a potential gene therapy for x-linked retinitis pigmentosa showcased improvements in microperimetry and a favorable safety profile.

Paulo Stanga, MD

Paulo Stanga, MD

Results of a phase 1 study examining use of a subretinal gene therapy show an adeno-associated virus serotype 8(AAV8) viral vector encoding retinitis pigmentosa GTPase regulator(RGPR) could be effective at treating x-linked retinitis pigmentosa.

Six-month results of the 24-month phase 1 open-label 3+3 6-dose escalation study, which revealed the gene therapy was well tolerated and resulted in improvements in microperimetry in half of participants at 1 month, were presented by Paulo Stanga MD, retinal surgery specialist of the London Vision Clinic, at the American Academy of Ophthalmology (AAO) 2019 Annual Meeting in San Francisco

In an effort to determine whether the AAV8 viral vector encoding retinitis pigmentosa GTPase regulator, investigators designed a dose-escalation interventional study of AAV8-RPGR in male subjects with genetically confirmed x-linked retinitis pigmentosa. A total of 18 patients were included by investigators for the study.

Inclusion criteria for the study included being 18 years of age or older and having documentation of a mutation in the RPGR. Patients were excluded if they had participated in previous gene therapy trials or a clinical trial with an investigational drug in the 12 weeks prior.

Primary outcomes measures for the current study included the proportion of patients with incidence of dose limiting toxicities and the incidence of treatment emergent adverse events. Secondary outcome measures included BCVA change, microperimetry change, SD-OCT change, and fundus autofluorescence changes.

Upon study completion, investigators observed AAV8-RPGR was well tolerated in all 18 study participants. A total of 65 adverse events occurred over the course of the trial and 20 were unrelated non-ocular events.

In regard to adverse events, most adverse events were mild(52/65) and resolved(40/65). Additionally, 18 events were possibly related to surgery and 13 to the treatment itself. One serious adverse event occurred during the study, which was a moderately severe decrease in visual acuity of unknown relationship and this was resolved. Stanga noted there was no DLTs or early discontinuations in the trial.

Microperimetry improvements were noted in 50% of treated eyes compared to 8.3% of untreated eyes at 1 months. At 3 months, 33% of treated eyes experienced an improvement in microperimetry while 0 untreated eyes experienced improvement. At 6 months, 36.6% of treated eyes saw improvement and, similar to the 3-month assessments, 0 untreated eyes experiences improvements.

“To finalize, we’ve demonstrated the positive dose-related improvements seen as early as 1 month across multiple microperimetry analyses,” Stanga said.

Stanga added the improvements in microperimetry observed in x-linked retinitis pigmentosa patients treated with AAV8-RPGR have led to the continuation of clinical trials for the potential treatment. The phase 1 dose escalation study was a part of the Part 1 program and the ongoing Part 2 program will include a phase 2/3 trial.

This study, “Early Evidence of Safety and Efficacy of AAV8-RPGR Gene Therapy for X-Linked Retinitis Pigmentosa,” was presented by Paulo Stanga, MD, at AAO 2019.

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