Adverum Biotechnologies, Inc. reported new 52-week topline data based on an evaluation of its lead gene therapy candidate, Ixoberogene soroparvovec (Ixo-vec), under clinical investigation for wet age-related macular degeneration (AMD) in the phase 2 LUNA trial.
First up: Adverum.
The California-based clinical-stage gene therapy company is developing a gene therapy-based pipeline of candidates to serve as a new standard of care for highly prevalent ocular diseases such as:
- Wet AMD
- Geographic atrophy (GA)
- Blue-cone monochromatism (BCM)
- Retinitis pigmentosa (RP)
- Friedreich’s ataxia
About this pipeline: These include durable, single-administration therapies intended to be administered in-office via a proprietary intravitreal (IVT) platform.
And what kind of technology are these therapies based on?
An adeno-associated virus (AAV) vector technology: AAV.7m8.
What it is: A transgene vector delivery technology designed to encode retinal cells to “become biofactories that provide robust, sustainable amounts of therapeutic proteins throughout the retina.”
The platform also features a peptide loop that enables AAV.7m8 to:
- Be injected via IVT
- Cross the inner limiting membrane (ILM)
- Transduce retinal cells
And the intended result: Targeting and potentially delivering a therapeutic payload at the location of the specific retinal disease (such as wet AMD, for Ixo-vec).
Now give me a rundown on Ixo-vec.
The company’s lead asset contains a vectorized aflibercept (an anti-vascular endothelial growth factor [VEGF]) coding sequence that’s controlled by a proprietary expression cassette optimized exclusively for IVT injection.
Specifically: Ixo-vec incorporates this AAV.7m8 platform to provide aflibercept as the therapeutic protein throughout the retina.
- The goal: Delivery of long-term VEGF inhibition.
Didn’t the FDA grant it a few designations?
Indeed. Ixo-vec has received both Fast Track and Regenerative Medicine Advanced Therapy (RMAT) designation for wet AMD.
To note: RMAT was just granted this past August (see our coverage).
Nice! Moving on this LUNA trial.
This multicenter, randomized, double-masked, parallel group phase 2 study (NCT05536973) evaluated Ixo-vec in two dose cohorts among wet AMD patients (n = 60; with 57 included in this recent data).
The doses:
- 2 × 1011 vg/eye (2E11)
- In combination with one of four corticosteroid treatment regimens
- 6 × 1010 vg/eye (6E10)
- In combination with one of four corticosteroid treatment regimens
The outcome measures:
- Primary:
- Ocular and non-ocular adverse events (AEs), measured up to Week 52
- Severity of ocular and non-ocular AEs, measured up to Week 52
- Mean change in best-corrected visual acuity (BCVA) from baseline, measured from baseline up to Week 52
- Secondary (measured from baseline up to 5 years):
- Participants from baseline who gained at least 5, 10, or 15 letters in BCVA
And that 52-week data?
The company reported that both Ixo-vec doses maintained visual and anatomic endpoints through the 52-week point.
See the numbers for BCVA and central subfield thickness (CST; 95% confidence interval [CI]).
And how was treatment burden reduction among patients?
Determined as the percentage reduced in mean annualized anti-VEGF injections, both doses achieved this: 88% and 92% for the 6E10 and 2E11 groups, respectively.
As for patients who were injection-free by Week 52, more than half of each group achieved this:
- 2E10: 54% (75% of patients with ≤1 injection)
- 6E10: 69% (79% of patients with ≤1 injection)
So overall?
Adverum reported that both Ixo-vec doses were well tolerated and local steroids were effective in managing inflammation—with no 6E10 patients exhibiting any inflammation at Week 52 (or any visit thereafter).
As for AEs: None were reported to be serious; all gene therapy-related occurrences were either mild or moderate.
- The most common: Dose-dependent anterior inflammation responsive to local corticosteroids and anterior pigmentary changes (and no vision impact).
- Notably: After Week 30, there was no onset inflammation
And what does this mean?
The company selected the 6E10 dose with topical eye drops for its pivotal program, as—based on these 52-week findings—that dosage was determined to provide “a predictable long-term favorable safety profile.”
What did the company have to say about this?
Adverum Chief Medical Officer Rabia Gurses Ozden, MD, stated that these findings “support our decision to advance the 6E10 dose and topical-eye drops-only prophylaxis into phase 3.”
Dr. Ozden also noted that, based on results from a patient preference survey among the study’s participants, “The vast majority preferred Ixo-vec over their prior intravitreal injections,” while 100% preferred the gene therapy over anti-VEGF treatments.
And the study’s researchers?
Principal investigator Charles Wykoff, MD, PhD, expressed similar sentiments, saying this data further establishes the potential of the 6E10 dose to “meaningfully reduce treatment burden for patients with wet AMD”—even for those with “highly active disease who are receiving frequent dosing.”
For reference: See how this data compares to previously reported 26-week findings from February 2024.
And lastly, what does the company have to say about this?
Based on this data—as well as 4-year findings from Adverum’s OPTIC program (see here for those results)—Dr. Ozden stated: “We have designed our Ixo-vec phase 3 pivotal program to establish gene therapy as a standard of care for all wet AMD patients.”