LUNA, OPTIC Data Support Long-Term Benefit of Ixo-Vec for Wet AMD

Charles Wykoff, MD, PhD

Credit: Retina Consultants of Texas

Topline 1-year results from the LUNA Phase 2 trial and 4-year follow-up of the OPTIC first-in-human trial supported the long-term potential of intravitreal ixoberogene soroparvovec (Ixo-vec) gene therapy for patients with neovascular (wet) age-related macular degeneration (nAMD).¹

Announced by Adverum Biotechnologies on November 18, 2024, 52-week efficacy data on the 6E10 dose and 4-year data on the 2E11 dose demonstrated the maintenance of visual and anatomic endpoints, with an ≥80% reduction in injection burden and ≥50% injection freedom with Ixo-vec treatment.

“The LUNA 52-week clinical data further establish that the 6E10 dose of Ixo-vec has the potential to meaningfully reduce treatment burden for patients with wet AMD, even among patients with highly active disease who are receiving frequent dosing,” Charles Wykoff, MD, PhD, director of research at Retina Consultants of Texas, and a principal LUNA investigator, said in a statement.¹ “Encouragingly, the 6E10 dose with extended prophylaxis also resulted in less inflammation.”

LUNA

LUNA is an ongoing double-masked, randomized Phase 2 trial in which 60 patients with nAMD were equally randomized to 2 dose cohorts: 6E10 or 2E11 vg/eye. The trial is designed to determine the optimal Ixo-vec dose and prophylactic regimen for Phase 3 registrational trials.

At the August 2024 cutoff date, 57 patients had completed the 52-week study visit, with 3 discontinuations from adverse events deemed unrelated to the study drug. In LUNA, the mean annualized prior anti-VEGF injections at baseline in the year before enrollment was 10.1.

Both doses of Ixo-vec maintained visual and anatomic endpoints through 52 weeks. These data showed least-squares mean best-corrected visual acuity (BCVA) change from baseline to Week 52 was –2.1 letters (95% CI, –4.8 to 0.7) and –1.8 letters (95% CI, –4.6 to 0.9) for the 6E10 and 2E11 doses, respectively.

Anatomic outcomes at Week 52 found the least-squares mean change in central subfield thickness (CST) was –10.2 µm (95% CI, –29.0 to 8.5) and –21.9 (95% CI, –40.4 to –3.3) in the 6E10 and 2E11 doses, respectively.

Both the 6E10 and 2E11 doses achieved an “industry-leading” reduction in treatment burden (88% and 92%, respectively) and the proportion of patients who were injection-free (54% and 69%, respectively) through 52 weeks. No patients at the 6E10 dose with topical eyedrops experienced inflammation at Week 52 or any subsequent visit.

A patient preference survey accompanying LUNA results found approximately 93% (n=56) of LUNA patients at 52 weeks preferred Ixo-vec, including the accompanying steroid regimen, over prior anti-VEGF therapies.

OPTIC

OPTIC is an ongoing, open-label, dose-ranging first-in-human trial that enrolled 30 patients with nAMD receiving frequent intravitreal injections (mean, 9.9 injections) to 2 Ixo-vec doses: 2E11 or 6E11. Patients received 6 weeks of prophylactic topical steroid eye drops or 13 days of prophylactic oral steroids. Set for 2 years, OPTIC included an optional 3-year extension.

At the data cutoff in August 2024, 21 patients completed the 4-year OPTIC study visit, with 2 discontinuations unrelated to Ixo-vec. With significant treatment needs at baseline, patients experienced long-term improvement with Ixo-vec through 4 years of follow-up.

Analysis showed an 86% reduction in annualized anti-VEGF injections, with a notable reduction in treatment burden across 4 years of Ixo-vec administration. Ixo-vec was reliably beneficial across 4 years, with close to 50% of patients injection-free throughout this period. Overall, Ixo-vec remained well-tolerated, with a generally favorable safety profile.

Ixo-vec Phase 3 Program

Adverum announced the 6E10 Ixo-vec dose with topical steroid prophylaxis was selected to progress into the pivotal program with 2 double-masked, randomized Phase 3 studies. The US-based ARTEMIS non-inferiority study will initiate in the first half of 2025 with a broad nAMD patient population including treatment-naive and experienced patients.

The planned primary endpoint, measured at an average of Weeks 52 and 56, is the non-inferiority change in mean BCVA from baseline between Ixo-vec and aflibercept 2 mg every 8 weeks, with a non-inferiority margin of -4.5 letters. Adverum indicated the trial design is based on end-of-Phase 2 feedback from the US Food and Drug Administration (FDA).

“These data from LUNA and OPTIC studies suggest a favorable benefit-risk profile for patients, which I believe many patients would consider if Ixo-vec were available in routine clinical practice,” Wykoff added.¹ “I look forward to working with the Adverum team as Ixo-vec advances toward pivotal studies next year.”

References

_{Adverum Biotechnologies, inc. - Adverum Biotechnologies Announces Positive 52-Week LUNA and 4-Year OPTIC Results, and Provides Key Pivotal Program Design Elements. November 18, 2024. Accessed November 22, 2024. https://investors.adverum.com/press_releases/news-details/2024/Adverum-Biotechnologies-Announces-Positive-52-Week-LUNA-and-4-Year-OPTIC-Results-and-Provides-Key-Pivotal-Program-Design-Elements/default.aspx}