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).
These data are being presented by Arshad Khanani, MD, MA, FASRS, on Monday, Feb. 12, at the 47th Annual Meeting of the Macula Society. The presentation titled “Ixoberogene soroparvovec (Ixo-vec) Intravitreal Gene Therapy for Neovascular Age-Related Macular Degeneration: Preliminary Results from the LUNA Phase 2 Study" is scheduled for 10:56am ET.
“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,” stated Laurent Fischer, MD, president and chief executive officer of Adverum Biotechnologies. “We are pleased with the emerging treatment profile of Ixo-vec, showing potential for best-in-class efficacy and over 90% of subjects having no or minimal inflammation with our 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. 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.”
Dr. Fischer continued, “Going into LUNA, we 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. 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.”
“Based on my experience as an investigator for over five 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,” said Dr. 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. “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.”
LUNA Trial Background and Baseline Demographics
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.
The LUNA trial builds on our experience with the OPTIC study, where landmark 2-year data was recently published in The Lancet’s eclinicalmedicine.
The data cut-off for these data is November 15, 2023, except for treatment burden reduction, which is of January 2, 2024.
LUNA Preliminary Efficacy and Safety Data Summary
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.
- 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.
- Visual (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)
- 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.
- Visual acuity was maintained at both dose levels - mean BCVA change from baseline to last visit (95% CI):
- Safety
- Preliminary 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.
Upcoming Ixo-vec Milestones
- LUNA 26-week interim analysis expected mid-2024
- Continued FDA and EMA formal and informal regulatory interactions
- Initiation of phase 3 trial expected H1’25