Six Month Findings from a Phase 1/2 Clinical Study of Subretinal Gene Therapy Drug AGTC-501 for X-Linked Retinitis Pigmentosa Show Clinically Meaningful Improvement in Macular Sensitivity

Abstract

Purpose : X-linked retinitis pigmentosa (XLRP) is an inherited retinal disease (IRD) characterized by night blindness beginning in adolescence, and progressive loss of peripheral vision that eventually leads to central vision loss. Gene therapy approaches for treating XLRP have explored the use of recombinant adeno-associated viral (rAAV) vectors to deliver a normal copy of the mutated gene responsible for retina cell loss. This is an initial report from an ongoing, Phase 1/2, open label, dose escalation clinical trial using an rAAV2 viral vector to deliver a functioning gene copy of retinitis pigmentosa GTPase regulator (RPGR) via subretinal injection.

Methods : Male participants (n=29), age ≥6, received subretinal injection of AGTC-501 (rAAV2tYF-GRK1-RPGR) into the central or peripheral macula region of the study eye. Participants were sequentially assigned to one of five dose groups to assess safety (primary outcome) and changes in visual function (secondary outcome), measured by MAIA microperimetry and best-corrected visual acuity (BCVA) as assessed by ETDRS. Patient data was analyzed 6 months post-treatment.

Results : Subretinal administration of AGTC-501 was well-tolerated across a wide dose range. The majority of adverse events were mild-moderate in severity, consistent with the subretinal injection and vitrectomy procedures, and/or concomitant prophylactic steroid regimen used to mitigate inflammation. Among the 21 centrally dosed participants, 18 had evaluable microperimetry data of which there were 8 responders, classified as a ≥7 decibel improvement in at least 5 loci within the central 36 loci macular area (p ≤ 0.05). Eleven of the 20 participants with evaluable BCVA data demonstrated improvement of ≥5 letters in the treated eyes compared to the fellow eyes (p = 0.001). Among peripherally treated patients, BCVA remained stable.

Conclusions : Robust safety and efficacy signals in the study eyes of participants who underwent subretinal administration of AGTC-501 were observed through month 6. There was clinically meaningful improvement in macular sensitivity and statistically significant improvement in BCVA for the study eyes vs. untreated fellow eyes. Follow-up is ongoing through 5 years to assess long-term safety and durability of response.

This is a 2021 ARVO Annual Meeting abstract.