Ixo-vec Yields Potentially Best-in-Class VEGF Injection Reduction for Wet AMD
The full 52-week analysis of the phase 2 LUNA trial are expected in the first half of 2025.
Charles Wykoff, MD, PhD
Credit: Retina Consultants of Texas
Ixoberogene soroparvovec (ixo-vec) gene therapy has demonstrated potentially best-in-class percentage of patients with wet age-related macular degeneration (AMD) remaining free of anti-vascular endothelial growth factor (VEGF) injections and reduction in annualized anti-VEGF injections.1
Updated, 26-week interim analysis data from the phase 2 LUNA trial (NCT05536973) were presented by Charles Wykoff, MD, PhD, Medical and Surgical Retina Specialist and ophthalmologist, Retina Consultants of Texas, and Member, scientific Advisory Board, Adverum, at the 42nd Annual Meeting of the American Society of Retinal Specialists in Stockholm, Sweden. These data were also shared in a webcast prior to the meeting.2
“In LUNA, the 26-week landmark analysis demonstrates that Ixo-vec has a potential best-in-class product profile, combining a favorable safety profile and an industry-leading proportion of patients who are free of injections, supporting our selection of the 6E10 dose with a local prophylactic regimen for Phase 3 pivotal studies,” Laurent Fischer, MD, president and chief executive officer, Adverum Biotechnologies, said in a statement.1 “Our pre-specified Patient Preference Survey, presented today for the first time, supports what we have long believed, that patients want to preserve long-term vision and be free of injections and are not deterred by corticosteroid prophylaxis. Over the next couple quarters, we plan to present data at important 9 month and 1-year timepoints. In OPTIC, nearly all patients who were injection free at 1 year continued to be injection free beyond 3 years.”
The ongoing, double-blind LUNA trial enrolled 60 patients with wet AMD to receive 6E10 or 2E11 vg/eye. The trial is also evaluating enhanced prophylactic regimens, with patients receiving 1 of 2 locally administered corticosteroid regimens, with or without oral prednisone. Enrolled participants had a mean annualized prior anti-VEGF injections of 10.1 (standard deviation [SD], 2.6), mean central subfield thickness of 350.6 (SD, 115.2), and mean best-corrected visual acuity (BCVA) of 72.3 (SD, 7.7).1
As of February 14, 2024, 58 patients had completed the 26-week study visit and 2 had discontinued due to AEs unrelated to study drug. Around one-third (35.6%) of patients in the Ozurdex + difluprednate prophylactic arm are not yet evaluable. Investigators have observed that 76% of patients in the 6E10 arm were injection free, with maintained visual acuity and fluid control. This arm also had a 90% reduction in mean annualized anti-VEGF injections.
“The LUNA trial was designed to answer a key question – whether lower doses of Ixo-vec combined with enhanced prophylactic regimens could demonstrate a product profile consistent with or better than that demonstrated in OPTIC. The landmark 6-month interim analysis has achieved this objective,” Star Seyedkazemi, PharmD, chief development officer, Adverum, added.1 “Importantly, at the LUNA 26-week interim analysis, 100% of 6E10 patients have no or minimal inflammation, and no participants received corticosteroids for treatment of inflammation beyond the scheduled prophylaxis. 76% of patients receiving 6E10 are injection free, with stable visual acuity and fluid control. In addition, in the 10 patients who were previously treated with the bi-specific therapyVabysmo™, all are free of injections, highlighting the ongoing unmet need even with recently approved anti-VEGF therapies.”
Based off positive data from the phase 2 trial, Adverum has selected the 6E10 vg dose combined with local prophylaxis for Phase 3 pivotal trials. In terms of safety, all participants on difluprednate alone had no or minimal inflammation and none received corticosteroids for inflammation beyond prophylaxis. There were no serious adverse events (AEs) related to treatment and no cases of episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion, or hypotony. A patient preference survey found that 88% of patients preferred ixo-vec over their prior anti-VEGF injections and 93% would opt to receive ixo-vec in the other eye.1
Adverum plans to present 9-month analysis data from LUNA in the fourth quarter of 2024 and 52-week analysis in the first quarter of 2025. The company plans to initiate the phase 3 trial in the first half of 2025.1
“Recent data demonstrating that up to 42% of patients stop treatment for wet AMD after 3 years highlights that difficulty with adherence to a regimen of repeated frequent intravitreal injections results in less-than-optimal vision outcomes. This underscores a tremendous unmet need for longer-acting anti-VEGF therapies. As a principal investigator in all of the Ixo-vec gene therapy clinical studies over the last 5+ years, I believe the latest data further demonstrate that Ixo-vec has the potential to shift the treatment paradigm for patients with wet AMD,” Wyckoff added.1 “From this LUNA landmark analysis and consistent with preclinical data, moving to the lower 6E10 dose resulted in less inflammation while maintaining clinical activity that would represent a significant reduction in treatment burden for many of my patients relative to the standard of care. Importantly, inflammation thus far appears to be clinically manageable and, when present, responsive to local corticosteroids that are well tolerated and routine to administer. I believe Ixo-vec has the potential to deliver a promising product profile for patients, and I look forward to working with the Adverum team as Ixo-vec advances toward pivotal studies next year.”
