Adverum Biotechnologies (ADVM) Study Update summary

Study design and objectives

• The LUNA Phase II trial evaluated Ixo-vec gene therapy in wet AMD patients, focusing on dose selection and corticosteroid prophylactic regimens to inform Phase III trials.

• The multicenter, double-masked, randomized trial enrolled 60 previously treated patients, split between 6E10 and 2E11 vg/eye doses, with a mean of 10 prior annualized anti-VEGF injections.

• Patients were randomized to four steroid prophylactic regimens, with primary endpoints including mean change in BCVA and incidence/severity of adverse events through 52 weeks; interim analysis at 26 weeks.

• Supplemental anti-VEGF injections were administered based on pre-specified criteria for disease activity.

• The study aimed to optimize efficacy, safety, and patient experience for future pivotal trials.

Efficacy results

• Ixo-vec achieved over 90% reduction in annualized anti-VEGF injections, with 76% (6E10) and 83% (2E11) of patients injection-free at 26 weeks.

• Visual acuity (BCVA) and central subfield thickness (CST) remained stable across both doses, with LS mean BCVA change at week 26 of -1.1 (6E10) and -2.2 (2E11) letters.

• Greater CST reduction was observed in patients with baseline CST >300 μm.

• In patients previously requiring multiple anti-VEGF agents, including VABYSMO, all were injection-free at six months.

• Aqueous aflibercept levels were consistent with long-term OPTIC data, supporting durable efficacy.

Safety and prophylactic regimens

• Ixo-vec was well tolerated at both doses, with no related serious adverse events; all related adverse events were mild or moderate, mainly dose-dependent anterior inflammation responsive to local corticosteroids.

• Enhanced local corticosteroid prophylaxis (difluprednate) minimized inflammation, with over 90% of patients experiencing no or minimal inflammation at all visits through week 26.

• Oral prednisone did not add benefit, and OZURDEX implant alone was insufficient; topical difluprednate alone was most effective.

• No cases of episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion, or hypotony were observed.

• No significant intraocular pressure issues were observed, and safety profile was improved over earlier studies.