The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to Adverum Biotechnologies, Inc. for its clinical-stage gene therapy candidate: Ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), intended to treat wet age-related macular degeneration (AMD).
First, a refresh on Adverum.
Formerly Avalanche Biotechnologies and based in Redwood City, California, the publicly traded clinical-stage gene therapy company is working to develop and establish gene therapy candidates and as a new standard of care for highly prevalent ocular diseases.
- The diseases: wet AMD, geographic atrophy (GA), blue cone monochromatism (BCM), retinitis pigmentosa (RP), and Friedreich’s ataxia
About these candidates: Adverum is developing and clinically evaluating a pipeline of durable, single-administration therapies designed for in-office use via a proprietary intravitreal (IVT) platform.
- Key to these therapies: adeno-associated virus (AAV) vector technology
Alrighty, now talk about this gene therapy candidate.
The company’s lead asset, Ixo-vec incorporates AAV.7m8, Adverum’s proprietary AAV capsid, intended to treat wet AMD.
Quick rundown on this AAV.7m8, please.
The AAV.7m8 transgene vector delivery technology is designed to “(encode) retinal cells to become biofactories that provide robust, sustainable amounts of therapeutic proteins throughout the retina.”
- In the case of Ixo-vec: The “therapeutic protein” refers to aflibercept, an anti-vascular endothelial growth factor (VEGF) protein
Plus: This platform also features a peptide loop that enables AAV.7m8 to:
- Be injected via IVT
- Cross the inner limiting membrane (ILM)
- Transduce retinal cells
The result: To target and potentially deliver a therapeutic payload at the location of the specific retinal disease (such as wet AMD, for Ixo-vec).
Gotcha. Now back to that candidate.
Ixo-vec contains a vectorized aflibercept coding sequence that’s controlled by a proprietary expression cassette optimized exclusively for IVT injection.And the intended effect of this: Delivery of long-term VEGF inhibition
Note: The therapeutic was previously granted FDA Fast Track Designation for wet AMD treatment.
Explain this designation.
RMAT is part of the FDA’s dedicated program designed for expediting the development and review process of investigational drug candidates intended to treat, modify, reverse, or cure a serious or life-threatening condition. Important to note: This designation is based on preliminary clinical evidence that indicates the specific therapy could potentially address an unmet need for the condition.
So! What’s the significance of this new designation?
Per Adverum CEO Laurent Fischer, MD, RMAT designation—as well as PRIority MEdicines (PRIME) designation in the European Union—is a validation of Ixo-vec’s potential to address the “significant unmet medical needs in treating nAMD.”“We look forward to continuing our close collaborations with both the FDA and (European Medicines Agency) EMA on our pivotal program and to sharing updates from regulatory discussions in the fourth quarter of this year,” Dr. Fischer stated.
Speaking of that data…
Ixo-vec was clinically evaluated in Adverum’s OPTIC clinical program, which investigated the gene therapy’s safety and efficacy for the first 2 years post-treatment via the phase 1 OPTIC study (NCT03748784) as well as the 5-year extension (NCT04645212) on long-term patient outcomes.
- Those findings: Ixo-vec was generally well-tolerated, demonstrating sustained durability and a promising safety profile post a single injection
And more recently?
In February 2024, Adverum reported positive 26-week data from the phase 2 LUNA study (NCT05536973) that found two dose levels of Ixo-vec demonstrated promising results in its primary outcomes measures.
The doses:
- 2 × 1011 vg/eye (2E11)
- 6 × 1010 vg/eye (6E10)
The outcome measures:
- Treatment burden reduction (90%+ for both)
- Supplemental injection-free rates (65%+ for both)
- Maintenance of outcomes for
- Best corrected visual acuity (BCVA)
- Central subfield thickness (CST)
- No adverse events
See more positive data coverage.
When is that trial expected to conclude?
Not until August 2028, according to Clinical Trials.
Definitely keep your eyes peeled between now and then for new data readings though …