Fresh off announcing 52-week phase 2 data, Adverum Biotechnologies, Inc. has also released long-term data from its OPTIC program that’s clinically evaluating Ixoberogene soroparvovec (Ixo-vec) for the treatment of wet age-related macular degeneration (AMD.
Start with a look at Adverum.
The clinical-stage gene therapy company’s candidate pipeline consists of durable, single-administration therapies intended to be administered in-office via a proprietary intravitreal (IVT) platform.
Its ocular disease focus includes:
- Wet AMD
- Geographic atrophy (GA)
- Blue-cone monochromatism (BCM)
- Retinitis pigmentosa (RP)
- Friedreich’s ataxia
And its technology platform?
AAV.7m8., an adeno-associated virus (AAV) transgene vector technology designed to encode retinal cells to “become biofactories that provide robust, sustainable amounts of therapeutic proteins throughout the retina.”
A peptide loop within the platform also enables AAV.7m8 to:
- Be injected via IVT
- Cross the inner limiting membrane (ILM)
- Transduce retinal cells
The end result: The targeted delivery of a therapeutic payload at the location of the specific retinal disease (such as wet AMD, for Ixo-vec).
Speaking of Ixo vec … give me the rundown.
As Adverum’s lead asset, Ix-vec is 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.
And its regulatory status: The candidate has received both Fast Track and Regenerative Medicine Advanced Therapy (RMAT) designation (granted this past August) for wet AMD.
Now let’s talk about this 4-year data.
Similar to the 3-year findings, Adverum reported that patients continued to “experience long-term benefit from Ixo-vec through at least 4 years of follow up.”
This included:
- Vision maintenance
- Anatomical improvement durability
- Sustained reduction in anti-VEGF treatment burden
How did the reduction in anti-VEGF injections differ over the years?
The company noted that patients had an 86% reduction in annualized anti-VEGF injections (through year 4)—which was similar to reductions seen in each of the previous years following Ixo-vec administration.
- Year 1: 84%
- Year 2: 81%
- Year 3: 84%
And the long-term benefits for Ixo-vec?
The findings only further supported the gene therapy, with almost 50% of patients injection-free through 4 years after treatment.
Specifically: A total of 78% and 88% of patients who were injection-free through year 1 and and year 2, respectively, were also injection-free through year 4.
Now to its safety profile.
Ixo-vec was found to be “generally well tolerated” and demonstrated a “favorable safety profile.”
All occurrences of inflammation were dose-dependent, had no impact on vision, and were responsive to local corticosteroids, according to Adverum.
Nice! Seems Ixo-vec has consistently performed well …
Indeed. In fact, Adverum President and CEO Laurent Fischer, MD, stated that the “consistent results” of the 52-week LUNA data (reported earlier) are only bolstered by the “OPTIC long-term data, where we have demonstrated stable therapeutic aflibercept levels through 5 years.”
Together, the data supports “a reliable, long-term benefit and a predictable safety profile,” he added.
So … what’s next?
The company is preparing to initiate two double-masked, randomized phase 3 trials to further reevaluate Ixo-vec (as a 6E10 vg/eye dose)—with the first anticipated for kickoff in H1 2025.
- About the first study: Dubbed “ARTEMIS,” the U.S.-based trial will enroll 284 patients.
- Design: Based on Adverum’s end-of-phase 2 feedback from FDA
- The participants: Treatment naïve and treatment-experienced wet AMD patients
- The setup: Participants will receive three monthly loading doses of aflibercept 2mg (once every 8 weeks) prior to Ixo-vec, with a sham in the control arm (to support masking)
- Note: All patients will be eligible for aflibercept supplemental injections and receive topical steroid eye drops
- The primary endpoint: Non-inferiority (NI) in mean BCVA change from baseline between Ixo-vec and aflibercept, measured at the average of Weeks 52 and 56
- NI margin: -4.5 letters
And lastly, what’s the expert input on all of this data thus far?
Charles Wkyoff, MD, PhD, a principal investigator for the Adverum’s phase 2 LUNA trial, spoke on the data from both LUNA and OPTIC program:
"These data… suggest a favorable benefit-risk profile for patients, which I believe many patients would consider if Ixo-vec were available in routine clinical practice.”
He added: “The totality of data indicates a predictable immune response with inflammation that, if it occurs, is manageable with local steroids, doesn’t impact vision, and ultimately resolves.
And from the company?
Adverum President and CEO Laurent Fischer, MD, noted that both OPTIC’s Ixo-vec dosage of 2E11 results and the phase 2 LUNA efficacy data at 52 weeks show maintenance of visual and anatomic endpoints “with over 80% reduction in injection burden and greater than 50% injection freedom.”
He concluded: “The data across both studies support a reliable long-term benefit and a predictable safety profile.”