– Study participants had an 81%-98% reduction in annualized anti-VEGF injections and demonstrated continuous aflibercept expression levels through three years
– Mean best-corrected visual acuity and central subfield thickness were maintained or improved in subjects treated with ADVM-022
-The Phase 2 LUNA trial is expected to dose the first subject in the third quarter of 2022 and preliminary data anticipated throughout 2023
REDWOOD CITY, Calif., July 15, 2022 (GLOBE NEWSWIRE) — Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases, today announced new data from the OPTIC study treating wet age-related macular degeneration (wet AMD) during the American Society of Retina Specialists (ASRS) 2022 Annual Meeting. New data presented are as of February 24, 2022 and include best-corrected visual acuity (BCVA) and central subfield thickness (CST) maintenance, as well as reduction in CST fluctuation after a single, in-office intravitreal (IVT) injection of ADVM-022, ixoberogene soroparvovec (Ixo-vec), in subjects requiring frequent anti-VEGF injections for their wet AMD.
“We are pleased to present our findings on BCVA and CST from the OPTIC trial, establishing that maintenance in both BCVA and CST, as well as a reduction in CST fluctuations, were sustained through at least two years, suggesting the long-term durability of Ixo-vec after a single IVT injection,” stated Richard Beckman, M.D., chief medical officer at Adverum Biotechnologies. “As several publications have recently highlighted, retinal CST fluctuations over time are associated with poor long-term visual outcomes for patients. The combination of durable maintenance of BCVA and reduced CST fluctuations in subjects who previously required frequent IVT injections further support our belief that Ixo-vec can provide better long-term benefit for wet AMD patients. We are excited by the possibility of extending the treatment benefit for this lifelong disease from the order of months to the order of years.”
Data Highlights as of February 24, 2022
- 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 ADVM-022.
- Mean BCVA (ETDRS) change from baseline to last visit was maintained or improved for two years post-treatment with ADVM-022 across both the 6×10^11 vg/eye (6E11) and 2×10^11 vg/eye (2E11) dose levels.
- Mean 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 ADVM-022 dose levels.
- In the 2E11 dose in subjects with neutralizing antibodies (NAb) titers <1:125, subjects demonstrated a mean BCVA improvement of 5.2 letters for two years following treatment with ADVM-022.
- ADVM-022 was well tolerated, with no participants in the 2E11 dose group requiring any topical corticosteroids to treat inflammation at most recent follow-up.
- No evidence of correlation between baseline NAbs and occurrence of inflammation or other safety events has been observed.
“We are excited to present these encouraging data, showing continuous and stable aflibercept expression for over three years in our OPTIC trial in subjects with wet AMD,” commented Laurent Fischer, M.D., president and chief executive officer at Adverum Biotechnologies. “As we recently announced, we completed our IND amendment with the U.S. Food and Drug Administration, received European Medicines Agency PRIME designation, and are preparing to initiate the Phase 2 LUNA trial of Ixo-vec in wet AMD. The LUNA trial was designed after a detailed data review from all 55 participants treated to date with a single ADVM-022 injection. Four new enhanced prophylactic steroid regimens will be evaluated in LUNA with the aim of providing steroid coverage during the period of peak immunogenicity. Our goal is to enhance the safety profile of ADVM-022 while building upon the impressive efficacy profile we continue to see in the OPTIC trial. We plan to dose the first subjects in the third quarter of 2022 and anticipate preliminary data from LUNA throughout 2023 and look forward to providing more detail on the expected timeline once we can assess the pace of enrollment.”
The LUNA trial is a multicenter, double-masked, randomized, parallel-group Phase 2 trial evaluating two doses of Ixo-vec, including 2E11 and a new, lower 6×10^10 vg/eye (6E10) dose, in up to 72 patients with wet AMD. The LUNA trial will assess four new enhanced prophylactic steroid regimens, including local steroids and combinations of local and systemic steroids to test the relative contribution of local versus systemic AAV exposure on ocular inflammation. Specific regimens include topical difluprednate (Durezol®), IVT Ozurdex®, or a combination of either topical Durezol® or IVT Ozurdex® with oral prednisone.
The trial will randomize the participants equally between the 2E11 and 6E10 Ixo-vec doses across four prophylactic steroid regimens and will be conducted at approximately 40 sites in the U.S. and Europe. The primary endpoints will be similar to the OPTIC trial and focus on mean change in BCVA and CST from baseline to one year, and incidence and severity of adverse events. Other data points will include protein expression of aflibercept starting at 10 weeks and an interim analysis at 26 weeks. The study will also evaluate the effectiveness and tolerability of the prophylactic steroid regimens.
“As an investigator in OPTIC, I have observed the potential of ADVM-022 to significantly reduce the treatment burden for my patients with neovascular age-related macular degeneration. In the latest data from the OPTIC trial, we have seen a manageable safety profile, robust aflibercept expression, and sustained anatomical improvements after two years following a single 2E11 dose of ADVM-022,” said Dante Pieramici, M.D., partner, California Retina Consultants, and presenter of the data at ASRS. “I look forward to participating as a LUNA investigator and building on the efficacy and safety profile in OPTIC with a new, lower 6E10 dose and to determine an optimal prophylactic steroid regimen for patients.”
About Wet Age-Related Macular Degeneration
Wet AMD, also known as neovascular AMD or nAMD, is an advanced form of AMD, affecting approximately 10% of patients living with AMD. Wet AMD is a leading cause of blindness in patients over 65 years of age, with a prevalence of approximately 20 million individuals worldwide living with this condition. The incidence of new cases of wet AMD is expected to grow significantly worldwide as populations age. AMD is expected to impact 288 million people worldwide by 2040, with wet AMD accounting for approximately 10% of those cases.
About OPTIC Trial of ADVM-022 in Wet AMD
ADVM-022 is Adverum’s clinical-stage gene therapy product candidate being developed for the treatment of wet AMD. ADVM-022 utilizes a propriety vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies that require a surgery to administer the gene therapy under the retina (sub-retinal approach), ADVM-022 has the advantage of being administered as a one-time IVT injection in the office and is designed to deliver long-term efficacy and reduce the burden of frequent anti-VEGF injections, optimize patient compliance, and improve vision outcomes for patients with wet AMD.
The OPTIC trial is designed as a multi-center, open-label, dose-ranging, safety and efficacy trial of ADVM-022 in patients with wet AMD who have demonstrated responsiveness to anti-VEGF treatment. Patients in OPTIC are treatment-experienced, and previously required frequent anti-VEGF injections to manage their wet AMD and to maintain functional vision.
About Adverum Biotechnologies
Adverum Biotechnologies (NASDAQ: ADVM) is a clinical-stage company that aims to establish gene therapy as a new standard of care for a number of highly prevalent ocular diseases with the aspiration of developing functional cures for these diseases to restore vision and prevent blindness. Leveraging the research capabilities of its proprietary, intravitreal (IVT) platform, Adverum is developing durable, single-administration therapies, designed to be delivered in physicians’ offices, to eliminate the need for frequent ocular injections to treat these diseases. Adverum is evaluating its novel gene therapy candidate, ADVM-022, ixoberogene soroparvovec (Ixo-vec), as a one-time, IVT injection for patients with neovascular or wet age-related macular degeneration. By overcoming the challenges associated with current treatment paradigms for these debilitating ocular diseases, Adverum aspires to transform the standard of care, preserve vision, and create a profound societal impact around the globe. For more information, please visit www.adverum.com.
Statements contained in this press release regarding events or results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include but are not limited to statements regarding Adverum’s plans to initiate a Phase 2 study in wet AMD to investigate the 2×10^11 vg/eye dose and a lower 6×10^10 vg/eye dose of ADVM-022, as well as new enhanced prophylactic steroid regimens, including local steroids and a combination of local and systemic steroids, planned for the third quarter of 2022, as well as the benefits Adverum expects from this trial, and the timing of preliminary data from the LUNA trial. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including risks inherent to, without limitation: Adverum’s novel technology, which makes it difficult to predict the timing of commencement and completion of clinical trials; regulatory uncertainties; enrollment uncertainties the results of early clinical trials not always being predictive of future clinical trials and results; and the potential for future complications or side effects in connection with use of ADVM-022. Additional risks and uncertainties facing Adverum are set forth under the caption “Risk Factors” and elsewhere in Adverum’s Securities and Exchange Commission (SEC) filings and reports, including Adverum’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2022 filed with the SEC on May 12, 2022. All forward-looking statements contained in this press release speak only as of the date on which they were made. Adverum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
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