Adverum Biotechnologies announced that it has gained alignment with the FDA on the clinical development path for ADVM-022, an investigational single, in-office intravitreal (IVT) injection gene therapy for the treatment of wet age-related macular degeneration (AMD). The company also reported financial results for the fourth quarter ended December 31, 2020, and provided a business update.
“Having clarity from U.S. regulators on our pivotal plans for ADVM-022 is a significant step forward in accelerating our mission to transform the lives of millions of patients around the world living with wet AMD and at risk of losing their vision,” Laurent Fischer, MD, chief executive officer at Adverum Biotechnologies, said in a company news release. “Based on the results in our OPTIC trial to date and our discussion with the FDA, we can now initiate two global phase 3 trials and have alignment on both clinical development and CMC requirements to support a BLA submission anticipated in 2024. Our team is well prepared to execute this new fast-to-market approach. In preparation of our potential commercialization of ADVM-022 targeting the treatment of millions of patients worldwide, we are expanding our CMC capabilities and investing in an in-house GMP manufacturing facility. Our goal is to deliver a one-time, in-office treatment that preserves patient sight for life.”
About the Global Phase 3 Program for ADVM-022 for the Treatment of Wet AMD
Based on the favorable safety and efficacy profiles observed to date from ADVM-022 in the OPTIC trial as well as interactions with the FDA, Adverum is planning to accelerate its clinical development program by conducting two global phase 3 trials targeted to initiate in parallel in the fourth quarter of 2021, according to a company news release. Pending successful outcomes of these trials, Adverum anticipates being able to submit its Biologics License Application for ADVM-022 for wet AMD in 2024.
The most recent OPTIC data presented at Angiogenesis 2021 demonstrated that patients who received 2 x 10^11 vg/eye of ADVM-022 experienced an 85% reduction in annualized anti-VEGF injections and two-thirds remained supplemental anti-VEGF injection free with median follow up of 48 weeks. Patients completing two years in OPTIC are being enrolled into an extension trial to be followed for up to 5 years.
The two phase 3 trials will study the efficacy and safety of two doses of ADVM-022 straddling the 2 x 10^11 vg/eye dose used in the OPTIC trial. In the phase 3 trials of approximately 450 patients each, patients newly diagnosed with wet AMD will be randomized to one of three arms, receiving a single IVT injection of either 3 x 10^11 vg/eye or 1 x 10^11 vg/eye of ADVM-022 compared to aflibercept IVT every 8 weeks. The primary endpoint will be non-inferiority to aflibercept based on change from baseline in Best Corrected Visual Acuity (BCVA) at 1 year.
“The remarkable durability and anatomical improvements seen with a single IVT injection of ADVM-022 in the OPTIC trial suggest that our therapy could provide clinically important benefits over currently marketed therapies and other late-stage programs in development for wet AMD,” Aaron Osborne, MBBS, chief medical officer at Adverum Biotechnologies, said in the news release. “In our OPTIC trial, we enrolled difficult-to-treat wet AMD patients who required frequent anti-VEGF injections to maintain their vision. Our phase 3 clinical trials will enroll newly diagnosed wet AMD patients and will be comparable to the designs of previous intravitreal anti-VEGF agents’ phase 3 trials. With our intravitreal approach, we look forward to working with clinical trial sites to rapidly enroll these studies for potential BLA submission in 2024.”
- Reed V. Tuckson, MD, joined Adverum’s board as an independent director. Dr. Tuckson brings extensive healthcare policy knowledge from his experience in multiple facets of the healthcare industry, including a 13-year tenure in senior leadership positions at UnitedHealth Group.
- Dawn Svoronos joined Adverum’s board as an independent director. Ms. Svoronos has three decades of global biopharmaceutical industry experience, spanning the United States, Canada, Europe, and Asia, gained during her 25-year career at Merck & Co.
- Christopher J. DeRespino joined Adverum as chief business officer, a newly created position. Mr. DeRespino will lead the company’s corporate strategy and global business development efforts. He brings significant biopharmaceutical experience gained at Amgen, Pfizer, and Onyx.
- Long-term preclinical data were published on ADVM-022 in Translational Vision Science & Technology (TVST), an official journal of the Association for Research in Vision and Ophthalmology (ARVO). This preclinical study in non-human primates is the longest safety and expression study to date, with measurements out to 30 months following a single IVT injection. The full online publication can be accessed from the TVST website.
- Patient enrollment was completed in the INFINITY Phase 2 trial to evaluate a single intravitreal injection of ADVM-022 for the treatment of diabetic macular edema (DME). Data from this randomized trial are expected in the second half of 2021. INFINITY is designed to demonstrate superior disease control compared to a single aflibercept injection, measured by time to worsening of DME disease activity. Additional objectives assess frequency of supplemental aflibercept to the study eye, visual acuity (BCVA), retinal anatomy (OCT), Diabetic Retinopathy Severity Scale (DRSS), and safety outcomes.
- Investing in a new state-of-the-art Good Manufacturing Practices (GMP) commercial facility in Durham, North Carolina, which is expected to be production-ready by the end of 2023. This facility capitalizes on Adverum’s internal AAV manufacturing expertise while providing security and flexibility to support the potential commercialization of ADVM-022.
- Licensed to LEXEO Therapeutics exclusive worldwide rights to its novel gene therapy candidate for cardiomyopathy due to Friedreich’s Ataxia.
ADVM-022 in Wet AMD:
- Initiate two global phase 3 pivotal trials for ADVM-022 in wet AMD in the fourth quarter of 2021
- Present long-term OPTIC data, including one-year data from Cohort 3 (2 x 10^11), in the second quarter of 2021
ADVM-022 in DME:
- Present clinical data from INFINITY phase 2 trial in the second half of 2021
GMP Commercial Manufacturing:
- Begin build-out of new GMP commercial manufacturing facility in North Carolina with multiple production suites, expected to be production-ready by the end of 2023 in preparation for commercialization of ADVM-022