– Data demonstrating that Ixo-vec was generally well tolerated and that a single intravitreal (IVT) injection can lead to stable and persistent aflibercept protein levels through three years in participants in the OPTIC extension study
– 81% – 98% reduction in mean annualized anti-VEGF injections after a single IVT injection of Ixo-vec, including 80% and 53% of participants supplemental injection free over two years across the 6×10^11 (6E11) and 2×10^11 (2E11) doses, respectively, regardless of neutralizing antibodies
– Mean best-corrected visual acuity (BCVA) and central subfield thickness (CST) were maintained or improved across both 6E11 and 2E11 doses
– All 2E11 participants were inflammation free at the end of the study
REDWOOD CITY, Calif., Nov. 04, 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 long-term follow-up data from the OPTIC study treating wet age-related macular degeneration (wet AMD) during The Retina Society Annual Meeting in Pasadena, California. New data presented include final two-year safety and efficacy assessment of Ixo-vec (ixoberogene soroparvovec, formerly referred to as ADVM-022), including reduction in annualized anti-VEGF injections, clinically relevant aflibercept protein levels and maintenance to improvement of mean best-corrected visual acuity (BCVA) and central subfield thickness (CST). OPTIC study participants could enroll in an extension study for an additional three years for a total of five years of follow-up.
“We are pleased to present our final two-year analysis from our OPTIC trial of Ixo-vec for the treatment of wet AMD. Ixo-vec demonstrated a robust treatment effect while maintaining a favorable safety profile, particularly at the 2E11 dose which was advanced to our Phase 2 LUNA trial,” stated Richard Beckman, M.D., chief medical officer of Adverum Biotechnologies. “We are particularly encouraged by the continuous and consistent aflibercept protein levels, through three years, as well as the maintenance to improvement in BCVA and CST from baseline while dramatically reducing the anti-VEGF treatment burden for patients. The longer-term follow-up data from OPTIC further strengthens our confidence in the design of the ongoing LUNA trial where we are evaluating the 2E11 dose and a new, lower 6×10^10 (6E10) dose, along with enhanced prophylactic steroid regimens.”
Data Highlights
- Ixo-vec was generally well tolerated with dose-dependent inflammation that was responsive to topical steroids.
- All 2E11 participants were inflammation free and did not require steroids to treat inflammation at the end of the study.
- OPTIC trial participants had an 81% – 98% reduction in annualized anti-VEGF injections, as well as continuous therapeutic aflibercept protein levels demonstrated through three years in extension study participants.
- 80% and 53% of the participants in the 6×10^11 (6E11) and 2×10^11 (2E11) dose groups, respectively, were supplemental injection free over two years.
- BCVA and CST were maintained to improved through at least two years at both the 6E11 and 2E11 dose levels.
“The complete data set from the OPTIC trial affirms that Ixo-vec may offer a potentially transformational treatment for wet AMD,” commented Carl Regillo, M.D., F.A.C.S., chief of retina services at Wills Eye Hospital, and presenter of the data at The Retina Society’s Annual Meeting. “A favorable benefit-risk profile resulting in an 81% reduction in annualized anti-VEGF injections was demonstrated in participants receiving the 2E11 dose regardless of baseline neutralizing antibodies, 53% of whom were supplemental injection free over two years. That is very promising and meaningful to patients, physicians, and the overall healthcare system. I look forward to serving as a LUNA Phase 2 investigator and gaining a further understanding of the safety and efficacy profile of Ixo-vec.”
Patient enrollment and dosing are currently underway in LUNA, a double-masked, randomized, Phase 2 trial. Adverum expects to conduct the trial at approximately 40 sites in the U.S. and Europe. Up to 72 subjects will be randomized equally between the 2E11 dose and new lower 6E10 dose and across four prophylactic steroid regimens. Specific regimens being evaluated include topical difluprednate (Durezol®), dexamethasone intravitreal implant (Ozurdex®), or a combination of either topical Durezol® or IVT Ozurdex® with oral prednisone, with the aim of establishing a prophylactic regimen with minimal need for inflammation management post prophylaxis.
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 projected 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, ixoberogene soroparvovec (Ixo-vec), is Adverum’s clinical-stage gene therapy product candidate being developed for the treatment of wet AMD. Ixo-vec utilizes a proprietary vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies that require surgery to administer the gene therapy under the retina (sub-retinal approach) Ixo-vec 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 Ixo-vec in participants 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 LUNA Trial of Ixo-vec in Wet AMD
Ixoberogene soroparvovec (Ixo-vec) is Adverum’s clinical-stage gene therapy product candidate being developed for the treatment of wet AMD. Ixo-vec utilizes an engineered, proprietary vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies that require surgery to administer the gene therapy under the retina (sub-retinal approach), Ixo-vec 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-vascular endothelial growth factor (VEGF) injections, optimize patient compliance, and improve vision outcomes for patients with wet AMD.
The LUNA trial is a multicenter, double-masked, randomized, parallel-group Phase 2 study evaluating two doses of Ixo-vec, including the 2×10^11 vg/eye (2E11) dose and a new, lower 6×10^10 vg/eye (6E10) dose, in wet AMD. The trial will randomize up to 72 participants equally across two doses and four prophylactic steroid regimens in 40 sites in the U.S. and Europe. The primary endpoints include the mean change in best-corrected visual acuity (BCVA) from baseline to one year and the incidence and severity of adverse events.
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 highly prevalent ocular diseases with the aspiration of developing functional cures 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, ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), 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.
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 the potential benefits of Ixo-vec, as well as the design of and patient enrollment in the ongoing LUNA trial evaluating the 2×10^11 (2E11) dose and a new, lower 6×10^10 (6E10) dose, along with enhanced prophylactic steroid regimens. 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 Ixo-vec. 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 June 30, 2022 filed with the SEC on August 11, 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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