Adverum Biotechnologies, Inc. released positive preliminary and efficacy safety data on Ixoberogene soroparvovec (Ixo-vec), its novel gene therapy candidate, from the ongoing phase 2 LUNA trial for wet age-related macular degeneration (AMD).
Hold up… didn’t we just hear about this company?
Indeed we did.
Last week, the Redwood City, California-based clinical-stage gene therapy company announced it raised $127.5 million for its gene therapy pipeline by selling an estimated 106.25 million shares of its common stock.
Gotcha. So what is Ixo-vec?
Ixoberogene soroparvovec (Ixo-vec), originally named ADVM-022—is a one-time, intravitreal (IVT) injection incorporating Adverum’s proprietary adeno-associated virus vector capsid (AAV.7m8, a transgene delivery vector technology) to treat wet AMD.
As a vectorized therapeutic protein (aflibercept), Ixo-vec has reportedly illustrated sustained durability and a favorable safety profile from one injection.
Even better: the majority of treated patients have demonstrated to be free of supplemental IVT injections at 1+ years.
Explain this AAV.7m8.
AAV.7m8 is designed to encode “retinal cells to become biofactories that provide robust, sustainable amounts of therapeutic proteins throughout the retina.”
Ixo-vec incorporates AAV.7m8 to transport a codon optimized sequence for aflibercept (the anti-vascular endothelial growth factor [VEGF] protein) in order to “transduce its production in retina cells.”
The resulting effect: potentially delivery of long-term VEGF inhibition following just one IVT injection in wet AMD patients.
What’s the clinical data on it so far?
Ixo-vec was evaluated in Adverum’s OPTIC clinical program, which is investigating its safety and efficacy for the first 2 years post-treatment with the dose-ranging OPTIC trial (NCT03748784) and then evaluating long-term patient outcomes up to 5 years (OPTIC extension study).
Click here for details on its well tolerance and long-term benefits.
Now this study.
The multicenter, randomized, double-masked, parallel group, phase 2 study (NCT05536973) is evaluating Ixo-vec as a single IVT injection in one of two doses (listed below) followed by one of four prophylactic corticosteroid treatment regimens.
- 2 × 1011 vg/eye (2E11)
- 6 × 1010 vg/eye (6E10)
Let’s talk participants.
A total of 69 participants (less than or 50 years of age) have been enrolled, all of whom must currently be receiving anti-VEGF therapy (minimum of two injections within 4 months prior to screening) and have demonstrated a meaningful response to such therapy.
Participants must also have a best-corrected visual acuity (BCVA) of 25–85 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the study eye at baseline and a BCVA of ≥ 35 ETDRS letters.
And the outcome measures?
Measured up to Week 52, the primary outcomes include:
- Ocular and nonocular adverse events (AEs)
- Severity of ocular and nonocular AEs
- Mean change in BCVA from baseline
Secondary outcomes are being measured from baseline up to 5 years and 60 months, according to Clinical Trials. These include:
- Participants from baseline who lose/gain at least 5, 10, or 15 letters in BCVA
- Mean change in BCVA
- Participants who are supplemental aflibercept injection-free
- Mean change in central subfield thickness (CST)
See the complete list here.
Now the findings.
Per Adverum, 26-week data focused on Ixo-vec illustrated the following:
- Treatment burden reduction
- Annualized reduction in anti-VEGF injections rates
- 2E11 dose = 94% (n=20)
- 6E10 dose = 90% (n=19)
- Injection-free rates
- 2E11 dose = 85% (n=20)
- 6E10 dose = 68% (n=19)
- Annualized reduction in anti-VEGF injections rates
- BCVA outcomes
- Visual acuity (VA) maintained at both dose levels, from baseline to last minute (95% Confidence Interval [CI]):
- 2E11 dose = -1.7 (-4.5, 1.2)
- 6E10 dose = +0.5 (-2.2, 3.3)
- Visual acuity (VA) maintained at both dose levels, from baseline to last minute (95% Confidence Interval [CI]):
- CST outcomes (μm)
- Anatomic endpoints maintained at both dose levels, from baseline to last visit (95% CI)
- 2E11 dose = -16.4 (-31.5, -1.3)
- 6E10 dose = -7.9 (-30.9, 15.0)
- Anatomic endpoints maintained at both dose levels, from baseline to last visit (95% CI)
The company noted that a sub-group analysis of participants with higher baseline CST found a greater reduction in CST (translating to Ixo-vec demonstrating a strong efficacy potential).
How was Ixo-vec’s safety profile?
Both dose levels resulted in improved inflammatory profiles, according to Adverum. These were also comparable to that of the phase 1 OPTIC study previously conducted on the gene therapy candidate.
Further, Ixo-vec was generally well-tolerated and was responsive to local steroids in the presence of intraocular inflammation (IOI).
Any adverse events?
None were reported.
How are the prophylactic regimens performing?
Adverum reported that certain regimens have been outperforming others to manage inflammation. Preliminary studies indicated that a combined regimen of Ozurdex (dexamethasone intravitreal implant) 0.7 mg + Durezol (difluprednate ophthalmic emulsion) 0.05% may be a favorable supplemental treatment approach for prophylaxis.
In fact, 90%+ of these participants had none to minimal inflammation with this combined treatment regimen. Oral corticosteroids, however, showed no incremental benefit.
Gotcha. So what’s next?
The company anticipates releasing a 26-week interim analysis on the LUNA trial by mid-2024 amidst regulatory interactions with the FDA for an eventual market submission.
Also on the docket: phase 3 trial initiation in the first half of 2025.
Arshad Khanani, MD, MA, FASRS, presented these findings during the 47th Annual Meeting of the Macula Society in a presentation titled, “Ixoberogene soroparvovec (Ixo-vec) Intravitreal Gene Therapy for Neovascular Age-Related Macular Degeneration: Preliminary Results from the LUNA Phase 2 Study.