ASRS 2024: Adverum Biotechnologies shares findings on Ixo-vec for wet AMD from LUNA Phase 2 trial

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Clinical-stage company Adverum Biotechnologies, which develops gene therapies for prevalent ocular diseases, announced findings from the 26-week interim analysis of the ongoing LUNA Phase 2 trial. The clinical trial investigates use of ixoberogene soroparvovec (Ixo-vec), delivered in a 6E10 vg/eye dose, in patients with wet age-related macular degeneration (AMD).¹ Charles C. Wykoff, MD, PhD, presented the data at the American Society of Retinal Specialists (ASRS) meeting in Sweden.

Speaking with Modern Retina, Laurent Fischer, MD, CEO of Adverum Biotechnologies, provided details from the study data. “What we show with these new data is that the new 6E10 dose, including a local prophylactic regimen with steroids, can maintain vision, maintain BCVA and central subfield thickness,” he said. “We saw that 76% of patients were free of injections, with overall a 90% reduction in treatment burden.”

In addition, Dr. Fischer said, Ixo-vec was well-tolerated, and no patients required additional steroids beyond the prophylactics to manage inflammation.

In a press release, Adverum Biotechnologies shared background information from the interim analysis.¹ Ixo-vec utilizes a proprietary vector capsid, AAV.7m8, which carries an aflibercept coding sequence under the control of a proprietary expression cassette. The LUNA trial is an ongoing double-masked, randomized Phase 2 trial; 60 patients with wet AMD were enrolled equally across two dose cohorts, 6E10 or 2E11 vg/eye. The LUNA trial is also evaluating enhanced prophylactic regimens, with patients receiving one of two locally administered corticosteroid regimens, with or without oral prednisone.

According to Adverum Biotechnologies, 100% of patients receiving difluprednate-alone (n=20) completed prophylaxis at the interim analysis, allowing evaluation of the prophylactic regimen. For patients receiving the 6E10 dose, 100% of patients reported no or minimal inflammation (0 or 0.5+ AC cells) at the 26-week timepoint. Among patients receiving the 2E11 dose, 90% of patients had no or minimal inflammation at the 26-week timepoint, and topical difluprednate effectively managed inflammation.

In a patient survey, 88% of patients indicated a preference for Ixo-vec over previously-received anti-VEGF injections. In the same survey, 93% of patients reported they would opt to receive Ixo-vec in the other eye.¹ Dr. Fischer said that these patient satisfaction results reflect a shifting perspective on long-term management of wet AMD.

“With gene therapy, this is truly regenerative medicine, where we can actually have a disease-modifying effect,” he said. “If this was cancer, we would call that remission, right? We see that in those patients. There's essentially no fluid in the majority of patients and stable vision.”

Dr. Fischer said that the existing landscape of anti-VEGF agents has good clinical outcomes, but falls short in terms of patient burden and risk to visual acuity over time. “If we look at the current treatment, we've seen that, in the two latest approved agents, we can extend treatment through every 12 to 16 weeks in some patients. But there's still a significant amount of injections required and fluctuation [of] the fluid,” he said. “We know that these fluctuations lead to poor vision outcomes. We also know that these are the best treatment scenarios, in clinical trials…[With Ixo-vec], we think we have years-long or lifelong benefits, instead of weeks or months.”

Dr. Fischer said the company hopes to initiate a Phase 3 trial as soon as possible. Adverum Biotechnologies is also searching for partners outside the United States to increase global distribution.

Reference

1. Adverum Biotechnologies Presents Positive Ixo-vec Clinical Data from the 26-Week Interim Analysis of the LUNA Phase 2 Trial at the 2024 ASRS Annual Meeting. Adverum Biotechnologies. Press release. Accessed July 17, 2024.