Ixo-Vec Granted RMAT Designation for Wet AMD
At the selected phase 2 dose, 76% of patients were injection free, with maintained visual acuity and fluid control.
Laurent Fischer, MD
Credit: Adverum
The FDA has granted Regenerative Medicine Advanced Therapy Designation to Adverum Biotechnologies’ ixoberogene soroparvovec (ixo-vec) gene therapy for the potential treatment of wet age-related macular degeneration (AMD).1
“The RMAT designation is based on the clinical data from Ixo-vec to date and recognizes the transformative potential of our gene therapy for patients with wet AMD,” Laurent Fischer, MD, president and chief executive officer, Adverum, said in a statement.1 “This validates that Ixo-vec has the potential to address the significant unmet medical needs in treating nAMD. With both RMAT and PRIME designations, we look forward to continuing our close collaborations with both the FDA and EMA on our pivotal program and to sharing updates from regulatory discussions in the fourth quarter of this year.”
Ixo-vec uses the adeno-associated virus vector AAV.7m8 to deliver an aflibercept coding sequence under the control of a proprietary expression cassette and is designed to be administered as a 1-time intravitreal injection in the physician’s office.
Adverum recently announced positive data revealing a potential best-in-class reduction in anti-VEGF injections from the phase 2 LUNA trial (NCT05536973) at the 42nd Annual Meeting of the American Society of Retinal Specialists in Stockholm, Sweden. The data were presented by Charles Wykoff, MD, PhD, Medical and Surgical Retina Specialist and ophthalmologist, Retina Consultants of Texas, and Member, scientific Advisory Board, Adverum.
READ MORE: 4D Molecular Therapeutics’ Wet AMD Gene Therapy 4D-150 Reduces Need for antiVEGF Injections
Sixty patients have been enrolled in the ongoing, double-blind LUNA trial to receive 6E10 or 2E11 vg/eye along with 1 of 2 locally administered corticosteroid regimens, with or without oral prednisone. As of February 14, 2024, 58 patients had completed the 26-week study visit and 2 had discontinued due to adverse events (AEs) unrelated to study drug. 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 AEs related to treatment and no cases of episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion, or hypotony.2
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. At this dose, 76% of patients were injection free, with maintained visual acuity and fluid control. This arm also had a 90% reduction in mean annualized anti-VEGF injections. 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.2
“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, said in a statement at that time.2 “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 therapy Vabysmo™, all are free of injections, highlighting the ongoing unmet need even with recently approved anti-VEGF therapies.”
