Adverum Announces Postive LUNA Phase 2 and OPTIC Long-Term Data on Gene Therapy for Wet AMD
Adverum Biotechnologies has released 52-week topline results from its phase 2 LUNA trial and new 4-year follow-up data from the OPTIC phase 1/2 study on its wet AMD gene therapy candidate Ixo-vec (AAV.7m8-aflibercept).
“We are thrilled to report 52-week LUNA data and 4-year OPTIC data that continue to support Ixo-vec as a transformative and potential best-in-class therapy, which may provide patients who have wet AMD with potentially life-long benefit and a predictable safety profile," Laurent Fischer, MD, president and chief executive officer of Adverum Biotechnologies, said in a company news release. "Both OPTIC 2E11 results and LUNA efficacy data at 52 weeks show maintenance of visual and anatomic endpoints with over 80% reduction in injection burden and greater than 50% injection freedom. These consistent results are bolstered by our OPTIC long-term data where we have demonstrated stable therapeutic aflibercept levels through 5 years. The data across both studies support a reliable long-term benefit and a predictable safety profile."
The data also showed that Ixo-vec maintained therapeutic aflibercept levels for up to 5 years, suggesting a durable effect that could reduce or eliminate the need for regular anti-VEGF injections. This is especially promising given that, in real-world scenarios, nearly 57% of wet AMD patients stop anti-VEGF treatment within 5 years, often resulting in significant vision loss, according to Adverum.
LUNA Phase 2 Trial: Key Findings at 52 Weeks
The LUNA study, a randomized, double-masked trial involving 60 patients, evaluated two dose levels (6E10 and 2E11 vg/eye) and various prophylactic regimens to prevent inflammation. At the 52-week mark, both doses of Ixo-vec demonstrated:
- Maintenance of Best Corrected Visual Acuity (BCVA) with a mean change close to baseline
- Significant reductions in Central Subfield Thickness (CST), a key measure of retinal fluid levels
- 88% (6E10) and 92% (2E11) reduction in anti-VEGF treatment burden
- Over half of the patients were injection-free at 1 year, with 75% requiring only one injection or fewer in the higher dose cohort
“Today’s LUNA 52-week data support our decision to advance the 6E10 dose and topical-eyedrops-only prophylaxis into phase 3," Rabia Gurses Ozden, MD, Chief Medical Officer at Adverum, said in the news release. "One of the unique, and in my view, profound aspects of this LUNA update was the near unanimous patient preference for Ixo-vec, as assessed via a pre-specified patient survey. The vast majority preferred Ixo-vec over their prior intravitreal injections. No patients on topical eyedrops alone stated that the steroid eyedrops were difficult to manage. And 100% of patients who received Ixo-vec 6E10 and eyedrops alone preferred Ixo-vec over prior anti-VEGF treatments.”
Patient preference surveys revealed strong support for Ixo-vec: 93% of patients preferred it over prior anti-VEGF therapies, with 100% of those on the 6E10 dose opting to receive treatment in both eyes if necessary, according to Adverum.
OPTIC Phase 1/2 Study: Durable 4-Year Outcomes
The OPTIC study, which enrolled patients with severe wet AMD requiring frequent anti-VEGF injections, showed impressive long-term efficacy over 4 years:
- An 86% reduction in annual anti-VEGF injections at year 4
- Nearly half of the participants remained injection-free for the entire follow-up period
- Stable aflibercept levels detected up to five years post-treatment, supporting the durability of Ixo-vec's gene therapy approach
Pivotal Program and Future Plans
Adverum is preparing to initiate its phase 3 ARTEMIS trial in the first half of 2025, designed to establish Ixo-vec as a standard of care for wet AMD. The pivotal trial will involve 284 patients in the US, with the primary goal of demonstrating noninferiority to standard anti-VEGF treatments in terms of BCVA.
The ARTEMIS study will use a double-masked, randomized design, incorporating both treatment-naïve and experienced wet AMD patients.