Pursuing Paradigm-Changing Gene Therapies

Adverum’s promising pipeline moves us ever closer to establishing ocular gene therapy as a new standard of care for debilitating ocular diseases.

pipeline may 2022
Advancing Ocular Gene Therapy

Ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022) is Adverum’s clinical-stage gene therapy product candidate being developed for the treatment of wet AMD. Ixo-vec utilizes a propriety vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. The current standard of care in wet AMD, a highly prevalent disease, requires frequent anti-vascular endothelial growth factor (anti-VEGF) injections in the eye and is a lifelong burden for many patients and their caregivers. We believe Ixo-vec has the potential to provide a durable, safe and cost-effective in-office treatment option that addresses the needs of these patients, and their families, as well as retina specialists and health systems worldwide.  Three-year aflibercept protein expression demonstrates continuous and consistent therapeutic levels from Ixo-vec in OPTIC study subjects with wet age-related macular degeneration (wet AMD).

OPTIC Clinical Program for Wet AMD

The typical way to evaluate anti-VEGF agents in clinical studies is to measure their short-term efficacy (i.e., 12 months or less). This approach, however, ignores or minimizes key factors that determine how well the therapy will work in the real world: a patient’s ability to maintain treatment regimens that require intravitreal injections every 4–12 weeks. Patients in OPTIC previously required very frequent anti-VEGF injections, with a median of 10 injections in the year preceding their enrollment.

Adverum’s OPTIC clinical program for wet AMD is investigating the safety and efficacy of Ixo-vec for the first two years post-treatment (the OPTIC trial) as well as evaluating the long-term patient outcomes for up to five years (the OPTIC Extension trial).

Latest data from the OPTIC trial evaluating a single intravitreal injection of Ixo-vec demonstrates:

  • OPTIC trial participants had an 81%-98% reduction in annualized anti-VEGF injections and demonstrated continuous therapeutic aflibercept protein expression levels through three years following a single, in-office intravitreal injection of Ixo-vec.
  • Mean best-corrected visual acuity (BCVA) change from baseline to last visit was maintained or improved for two years post-treatment with Ixo-vec across both the 6×1011 vg/eye (6E11) and 2×1011 vg/eye (2E11) dose levels.
  • Mean central subfield thickness (CST) was reduced by 55.7 µm at the 6E11 dose (p=0.014) and by 95.9 µm at the 2E11 dose (p=0.015) and maintained for two years following treatment across both Ixo-vec dose levels.
  • Ixo-vec was well tolerated, with no participants in the 2E11 dose group requiring any topical corticosteroids to treat inflammation at most recent follow-up (Feb. 24, 2022).
  • No evidence of correlation between baseline neutralizing antibodies (NAbs) and occurrence of inflammation or other safety events has been observed.
  • The OPTIC data supports the initiation of a Phase 2 study in wet AMD investigating the 2E11 dose and a lower 6×1010 (6E10) vg/eye dose of Ixo-vec, as well as new enhanced prophylactic steroid regimens, including local steroids and a combination of local and systemic steroids.

View of Ixo-vec from a
Wet AMD Specialist

“The long-term efficacy seen in the OPTIC trial after a single injection of Ixo-vec has been remarkable for my patients, who required frequent injections prior to entering the trial. The long-term safety data supports using the lower 2E11 vg/eye dose and a new lower 6E10 vg/eye dose with an enhanced steroid prophylaxis regimen. I look forward to evaluating Ixo-vec’s potential to provide a safe and durable gene therapy from a single, in-office injection in patients with wet AMD in the upcoming Phase 2 trial.”

Arshad Khannani, OPTIC Investigator and Adverum Scientific Advisory Board Member

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