Adverum Biotechnologies Presents Three-Year Aflibercept Protein Expression and Improvement in Anatomic Outcomes After a Single IVT Injection of ADVM-022 in the OPTIC Study in Wet AMD

Rhea-AI Summary

Adverum Biotechnologies (ADVM) announced new data from the OPTIC study on its gene therapy candidate, ADVM-022, for treating wet age-related macular degeneration (AMD). Findings indicate that aflibercept protein levels remain therapeutically effective for three years after a single dose. The study also reported an 81% reduction in anti-VEGF injections and a 70% decrease in CST fluctuations for patients with specific neutralizing antibody titers. Adverum plans to initiate a Phase 2 study later this year to further evaluate ADVM-022's efficacy and safety.

Positive

• Therapeutic aflibercept expression sustained for three years post ADVM-022 injection.
• 81% reduction in mean annualized anti-VEGF injections among all participants.
• 93% reduction in injections for patients with neutralizing antibody titers <1:125 at 2E11 dose.
• 70% reduction in CST fluctuations for patients with NAbs <1:125 after treatment.

Negative

• None.

- Three-year aflibercept protein expression demonstrates continuous and consistent therapeutic levels from ADVM-022 in OPTIC study subjects with wet age-related macular degeneration (wet AMD)

- New data highlight ADVM-022 reductions in mean annualized anti-VEGF injections range from 81% in all OPTIC subjects to 93% in subjects with neutralizing antibody titers <1:125 at the 2 X 10^11 vg/eye dose

REDWOOD CITY, Calif., June 09, 2022 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ocular and rare diseases, today announced new data from the OPTIC study treating wet age-related macular degeneration (wet AMD) during the Macula Society Annual Meeting in Berlin, Germany. New analyses presented include three-year aflibercept protein expression and improved anatomical outcomes in subjects treated with ADVM-022.

“We are thrilled to highlight new data indicating that therapeutic levels of aflibercept expression, following a single administration of ADVM-022, are sustained out to three-years, demonstrating its potential for continuous long-term clinical benefit. Additionally, we are pleased to present compelling data relating to patients’ baseline levels of neutralizing antibodies and treatment efficacy. In OPTIC, over 80% of screened patients had neutralizing antibody titers <1:125 against the human engineered AAV.7m8 capsid. In the 2x10^11 vg/eye dose group, subjects with baseline neutralizing antibody titers to AAV.7m8 <1:125 showed significant improvement in macular fluid as measured by central subfield thickness (CST) improvement and fewer fluctuations post-treatment,” commented Richard Beckman, M.D., chief medical officer at Adverum Biotechnologies. “Fluctuations in macular fluid as measured by CST are associated with the current treatment paradigm of frequent repeated bolus anti-VEGF injections. Recent literature has demonstrated that greater fluctuations are associated with poor long-term visual outcomes. These data suggest that by delivering continuous levels of aflibercept, ADVM-022 can dramatically reduce fluctuations in CST which may translate into better long-term vision.”  

Data Highlights

• ADVM-022 provided continuous and consistent therapeutic aflibercept expression levels through three years following a single ADVM-022 injection.
• ADVM-022 was well tolerated, with no participants in the 2x10^11 vg/eye (2E11) dose group requiring any topical corticosteroids to treat inflammation at most recent follow up.
• Over 80% of patients screened for the OPTIC trial had baseline NAbs titers of <1:125 against AAV.7m8, our engineered proprietary capsid enabling intravitreal (IVT) delivery.
• The 2E11 dose in subjects with neutralizing antibody (NAbs) titers <1:125, provided sustained therapeutic aflibercept levels comparable to the 6x10^11 (6E11) dose.
• The mean annualized anti-vascular endothelial growth factor (VEGF) injection rate was reduced by 81% in all participants receiving 2E11 and 93% in participants with NAbs titers <1:125, suggesting that those with baseline NAbs to AAV.7m8 <1:125 demonstrated more robust aflibercept protein expression and required even fewer supplemental anti-VEGF injections.
• There was a 70% reduction in annualized rate of CST fluctuation (± 50 µm) observed in OPTIC participants with NAbs <1:125 after treatment with ADVM-022 at 2E11.
• In OPTIC, no evidence of correlation between baseline NAbs and occurrence of inflammation or other safety events has been observed.
  

The initiation of a Phase 2 study in wet AMD investigating the 2E11 dose and a lower 6x10^10 (6E10) 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, is planned for the third quarter of 2022.

“As a practicing physician with a deep understanding of the wet AMD patient population’s needs, the longer duration of efficacy from weeks to years, as well as the favorable safety profile of ADVM-022 warrants further development of the 2E11 dose, and given the NHP data showing similar aflibercept expression at 6E10 vg/eye, I am eager to see the efficacy and safety profile of the new, lower 6E10 dose in the upcoming Phase 2 trial,” stated Szilárd Kiss, M.D., Bob and Dolores Hope – Robert M. Ellsworth, M.D. Distinguished Associate Professor in Ophthalmology. 

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 

ADVM022 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 gene therapy company targeting unmet medical needs in serious ocular and rare diseases. Adverum is evaluating its novel gene therapy candidate, ADVM-022, as a one-time, intravitreal injection for the treatment of patients with neovascular or wet age-related macular degeneration. For more information, please visit www.adverum.com.

Forward-looking Statements

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 2x10^11 vg/eye dose and a lower 6x10^10 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. 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; 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.

Inquiries

Anand Reddi
Vice President, Head of Corporate Strategy and External Affairs & Engagement
Adverum Biotechnologies, Inc.
T: 650-649-1358

Investors

Laurence Watts
Gilmartin Group
T: 619-916-7620
E: laurence@gilmartinir.com

Media

Megan Talon
Associate Director, Corporate Communications
Adverum Biotechnologies, Inc.
T: 650-649-1006
E: mtalon@adverum.com

FAQ

What were the results of the OPTIC study for ADVM (ADVM-022)?

The OPTIC study showed that ADVM-022 maintains aflibercept levels for three years, reducing anti-VEGF injection needs by up to 93% in certain patients.

What is the significance of the neutralizing antibody titers in the OPTIC study?

Patients with neutralizing antibody titers <1:125 experienced better treatment outcomes, including fewer anti-VEGF injections and reduced CST fluctuations.

When is Adverum planning to start its Phase 2 study for ADVM-022?

Adverum plans to initiate a Phase 2 study in the third quarter of 2022 to further evaluate ADVM-022's efficacy at different dosages.

What condition does ADVM-022 aim to treat?

ADVM-022 is designed for the treatment of wet age-related macular degeneration (AMD), a leading cause of blindness in older adults.