Adverum’s Ixo-Vec for Wet AMD Evaluated in 3-Year Data from OPTIC Extension Study

Adverum Biotechnologies announced updated data from the OPTIC extension study of patients with wet age-related macular degeneration (AMD) and a summary of previously announced aflibercept protein levels from the LUNA study were presented during the Retina Subspecialty Day at AAO 2023 in San Francisco.

Adverum’s ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022) is a clinical-stage gene therapy product candidate for the treatment of wet AMD. Ixo-vec utilizes the company’s vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette.

According to the company, Ixo-vec is designed to be administered as a one-time intravitreal (IVT) injection in the physician’s office, deliver long-term efficacy, reduce the burden of frequent antivascular endothelial growth factor (VEGF) injections, optimize patient compliance, and improve vision outcomes for patients with wet AMD.

The presentation, “ADVM-022 Intravitreal Gene Therapy for Neovascular AMD: Preliminary Data from the Phase 2 LUNA Trial and 3-Year Results From the Phase 1 OPTIC-Extension Trial,” was delivered by Carl D. Regillo, MD, Chief of the Retina Service at Wills Eye Hospital in Philadelphia.

As summarized by the company, the OPTIC 3-year extension data include the following highlights:

• Patients in the OPTIC extension trial continue to experience long-term benefit from Ixo-vec through 3 years of follow-up, including maintenance of vision, durability of anatomical improvements, and sustained reduction in anti-VEGF treatment burden.
• Patients at the 2E11 dose had an 84% reduction in annualized anti-VEGF injections, with 53% of the participants at the 2E11 dose receiving no supplemental injections through 3 years.
• Aflibercept protein levels have been sustained through follow-up, which is up to 4.5 years post-treatment.
• Best corrected visual acuity (BCVA) was maintained and central subfield thickness (CST) was improved through 3 years.
• Ixo-vec was generally well tolerated with dose-dependent inflammation that was responsive to topical steroids.

The company outlined the LUNA aflibercept protein data highlights, baseline characteristics, and clinical program milestones that were presented by Dr. Regillo, as follows:

• Aflibercept protein data suggest Ixo-vec at the 2E11 and 6E10 doses deliver similar levels of aflibercept that are both within the therapeutically active range based on OPTIC and nonhuman primate data.
• The LUNA trial population has comparable injection frequency and other baseline characteristics, with slightly better visual acuity and fluid control, compared to the study population of OPTIC.
• In particular, the mean annualized anti-VEGF injection rate in the 12 months before Ixo-vec treatment in LUNA is 9.9 injections, indicating that these patients require frequent injections, administered approximately every 6 weeks.
• The LUNA preliminary efficacy and safety data are expected in Q4 2023; additional LUNA data, including the 26-week interim analysis, are expected in mid 2024.

“The long-term follow-up data from the OPTIC trial continue to affirm that Ixo-vec offers a potentially transformational treatment for wet AMD,” commented Dr. Regillo in the Adverum press release. “A favorable benefit-risk profile resulting in an 84% reduction in annualized anti-VEGF injections was demonstrated in participants receiving the 2E11 dose, with 53% of patients continuing to be free from supplemental injections at 3 years after a single IVT injection.”

Dr. Regillo continued, “Taken together, the efficacy and safety at the 2E11 dose in the OPTIC trial underscore Ixo-vec’s potential as a promising treatment option for wet AMD patients addressing real-world unmet needs. I look forward to learning more from the ongoing Phase 2 LUNA trial.”

Adverum advised that Ixo-vec has been granted FDA Fast Track designation for Ixo-vec for the treatment of wet AMD; additionally, it has received PRIME designation from the European Medicines Agency and the Innovation Passport from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency for the treatment of wet AMD.