Charles C. Wykoff, MD, PhD: Interim Analysis on Ixo-Vec Gene Therapy for nAMD

Interim results from the LUNA study demonstrated the efficacy and tolerability of ixoberogene soroparvovec (Ixo-vec) intravitreal gene therapy for neovascular age-related macular degeneration (nAMD). These interim Phase 2 data were presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting.

These data showed a single Ixo-vec intravitreal injection led to a 90–95% reduction in annualized anti-VEGF injections and maintenance of visual and anatomic outcomes in treatment-experienced patients with nAMD.

“The core point of LUNA was the safety analysis. Overall, there were no serious adverse events that were related to Ixo-Vec, and all the related adverse events were mild or moderate, most commonly anterior chamber cellular inflammation response to the topical steroids,” presenting investigator Charles C. Wykoff, MD, PhD, director of clinical research at Retina Consultants of Texas, told HCPLive.

Ixo-vec, previously known as ADVM-02, has demonstrated vision preservation and sustained reduction in macular fluid through 3 years after a single intravitreal injection in the first-in-human trial, OPTIC. The ongoing multi-center, randomized, double-masked 6-month LUNA study evaluated the optimal dose of Ixo-vec combined with enhanced corticosteroid prophylactic regimens for nAMD.

Eligible participants were randomized between two Ixo-vec doses (6 x 1010 and 2 x 1011 vg/eye) and multiple prophylactic regimens, including local corticosteroids with and without oral prednisone. Primary endpoints were the incidence and severity of adverse events and the mean change in best-corrected visual acuity from baseline to Week 52.

This pre-specified interim analysis occurred after the completion of the Week 26 visit.

At the interim analysis cutoff, 58 participants were enrolled, with a mean follow-up duration of 35.2 weeks. Before Ixo-vec dosing, the mean number of annualized anti-VEGF injections was 10.1, and the mean BCVA and CST were 72.3 ETDRS letters and 350.6 µm, respectively.

Upon analysis, Ixo-vec showed a significant proportion of patients remained injection-free at both doses at Week 26. Of the dosing cohorts, 76% and 83% of participants, respectively, required no supplemental anti-VEGF injections through Week 26.

Ixo-vec also led to a significant reduction in mean annualized anti-VEGF injections at week 26. Notably, the mean annualized anti-VEGF injection frequency was reduced by 90% and 95% in the 6E10 and 2E11 vg/eye cohorts, respectively.

Visual acuity was maintained with a least-squares mean change from baseline to Week 26 of –1.1 and –2.2 ETDRS letters for the 6E10 and 2E11 vg/eye cohorts, respectively. Fluid control was also maintained, with a least-squares mean CST change of –12.6 µm and –12.0 µm in these cohorts, respectively.

Safety data showed Ixo-vec was well-tolerated at both doses and linked to no serious adverse events. All Ixo-vec-related adverse events were mild or moderate, with no cases of episcleritis, retinitis, vasculitis, choroiditis, vascular occlusive events, or hypotony.

A safety subgroup analysis of the Difluprednate-Alone prophylactic regimen showed that 100% (n = 20) of patients completed their prophylaxis. Inflammation was dose-dependent and responsive to local corticosteroids.

All (n = 10) patients at the 6E10 dose showed no or minimal inflammation (0 or 0.5+ anterior chamber cells) at the interim analysis timepoint. None of these participants received corticosteroids for inflammation beyond scheduled prophylaxis.

In the 2E11 dose group, 90% (n = 9) of patients showed no or minimal inflammation at 26 weeks. When present, topical difluprednate was reported to manage inflammation effectively.
LUNA is ongoing and will continue to evaluate the safety and efficacy profile of Ixo-vec in nAMD to inform future Phase 3 registrational trials.

"Overall, this is an interim analysis, pre-specified at Week 26 and ultimately this will be a 1-year trial and then a 4-year extension beyond that," Wykoff told HCPLive.

Disclosures: Relevant disclosures for Wykoff include Adverum Biotechnologies, Apellis, Genentech, Iveric, Regeneron, and others.

Reference

_{Wykoff CC. Ixoberogene Soroparvovec (Ixo-vec) IVT Gene Therapy for Neovascular AMD: First-Time 26-Week Interim Analysis Results From the Phase 2 LUNA Study. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}