Adverum Biotechnologies releases positive preliminary efficacy, safety data from LUNA Phase 2 trial of Ixo-vec in patients with wet AMD

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Adverum Biotechnologies Inc announced preliminary safety and efficacy data from the ongoing LUNA Phase 2 trial in patients with wet age-related macular degeneration (AMD).

The data are being presented today by Arshad Khanani, MD, MA, FASRS, at the 47th annual meeting of the Macula Society in a ppresentation titled “Ixoberogene soroparvovec (Ixo-vec) Intravitreal Gene Therapy for Neovascular Age-Related Macular Degeneration: Preliminary Results from the LUNA Phase 2 Study.”

Laurent Fischer, MD, president and chief executive officer of Adverum Biotechnologies, pointed out in a news release wet AMD is a leading cause of blindness in people over the age of 65, requiring life-long anti-VEGF injections.

“Our goal with Ixo-vec is to provide patients virtually injection-free management of their wet AMD lasting years and potentially for life,” Fischer said in a statement.

Fischer added the company is pleased with the emerging treatment profile of Ixo-vec, showing potential for efficacy and more than 90% of subjects having no or minimal inflammation with the company’s go-forward local prophylactic regimen.

“Underscoring the potential best-in-class profile of Ixo-vec, these early activity results were seen in hard-to-treat patients, who received over 9 annualized injections in the year prior to receiving Ixo-vec,” Fischer added in the statement. “Going into LUNA, we looked to replicate the robust clinical activity seen in OPTIC, in which patients continued to see clinical benefit through 3 years, with measured stable aflibercept through 4.5 years. We are proud to build upon our pioneering efforts with the most mature dataset and longest follow-up of all wet AMD intravitreal gene therapies currently in development.”

Moreover, Fischer noted that as LUNA started, the company also looked to establish that an enhanced prophylactic regimen combined with highly active doses of Ixo-vec would further enhance its long-term benefit-risk profile.

“With these early data, we are pleased with the promising profile of Ozurdex plus difluprednate which we expect to be our go-forward regimen,” Fischer pointed out in the news release. “We look forward to sharing the maturing LUNA dataset with the goal of confirming the optimal dose(s) and prophylactic regimen for pivotal studies and with the plan to present our 26-week interim analysis in the middle of 2024.”

Khanani noted that in his experience as an investigator for more than 5 years across multiple clinical trials with Ixo-vec for wet AMD, “it’s promising to see the sustained disease control and a significant treatment burden reduction after a single intravitreal injection of Ixo-vec in previously treated patients with wet AMD.”

Khanani, managing partner and director of Clinical Research at Sierra Eye Associates, Clinical Associate Professor at University of Nevada, Reno and principal investigator in LUNA trial, concluded he is looking forward to the next step.

“Ixo-vec has the potential to shift the treatment paradigm for patients with wet AMD and I look forward to working with the Adverum team to advance Ixo-vec into pivotal studies,” he said in the release.

About the LUNA trial

According to the company, the LUNA trial is an ongoing double-masked, randomized, Phase 2 trial. 60 patients with wet AMD were enrolled equally across two dose cohorts, 2E11 and 6E10 vg/eye. The study is designed to assess optimized prophylactic regimens, with patients receiving one and/or two locally administered corticosteroid regimens, with or without oral prednisone.

Adverum added the LUNA trial builds on its experience with the OPTIC study, where landmark 2-year data was recently published in The Lancet.

The data cut-off for these data is November 15, 2023, except for treatment burden reduction, which is of January 2, 2024.

Preliminary Efficacy and Safety Data Summary

According to the release, both the 2E11 and 6E10 doses demonstrated maintenance of visual and anatomic outcomes. Notably, both doses resulted in a potentially best-in-class reduction in annualized anti-vascular endothelial growth factor (VEGF) injections and the percentage of patients remaining free of annualized injections, with data trending similar to or better than the OPTIC study.

For treatment burden reduction, at 26 weeks, Ixo-vec demonstrated annualized reduction in anti-VEGF injection rates of 90% (n=19) at 6E10 and 94% (n=20) at 2E11. At 26 weeks, Ixo-vec demonstrated injection free rates of 68% (n=19) at 6E10 and 85% (n=20) at 2E11.

The release also noted that for best corrected visual acuity (BCVA) and anatomic (CST) outcomes, visual acuity was maintained at both dose levels - mean BCVA change from baseline to last visit (95% CI):

• 2E11: -1.7 (-4.5, 1.2)
• 6E10: +0.5 (-2.2, 3.3)

Moreover, the company noted that anatomic endpoints were maintained at both dose levels - mean CST (μm) change from baseline to last visit (95% CI):

• 2E11: -16.4 (-31.5, -1.3)
• 6E10: -7.9 (-30.9, 15.0)
• In a sub-group analysis of patients with higher baseline CST, a greater reduction in CST was demonstrated, indicating the robust efficacy potential of Ixo-vec gene therapy.

Preliminary safey data suggest corticosteroid prophylaxis optimization at both the 2E11 and 6E10 doses appears to result in improved inflammatory profiles in LUNA as compared to OPTIC study results.

• Ixo-vec was generally well-tolerated, and when present intraocular inflammation was responsive to local corticosteroids.
• No Ixo-vec related serious adverse events were reported.
• No episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion or hypotony were reported.
• Preliminary data indicate that select prophylactic regimens are outperforming others that do not provide sustained prophylaxis.
• Early on in the study, the company implemented a protocol amendment to augment the Ozurdex containing regimens with a course of Durezol eye drops.
• Preliminary data indicate that the amended Ozurdex + Durezol regimen may be the favorable prophylactic regimen for future pivotal studies.
• In this potential “go-forward” regimen, the vast majority of patients had no inflammation, with over 90% of these patients having no or minimal inflammation. Oral corticosteroids showed no incremental benefit.