– Wet age-related macular degeneration (wet AMD) is a bilateral disease with an incidence of second eye neovascularization (nAMD) of up to 42% in the first 2-3 years after first eye diagnosis –
– Stepwise administration of Ixo-vec in non-human primates (NHP) resulted in peak aflibercept protein levels in the second eye within the target therapeutic range, supporting the feasibility of bilateral dosing. rice field –
– The No Adverse Effect Level (NOAEL) for NHP was confirmed at a human equivalent dose of 2×10^11 vg/eye (2E11), supporting the 2E11 and 6×10^10 vg/eye (6E10) doses of Ixo-vec being evaluated in the ongoing Phase 2 LUNA trial –
REDWOOD CITY, Calif., April 23, 2023 (GLOBE NEWSWIRE) — Adverum Biotechnologies, Inc. (Nasdaq: ADVM) is determined to establish gene therapy as a new standard of care for a highly prevalent eye disease. Aiming to be a company in the clinical stage. This data was featured in an oral presentation at the Society for Vision and Ophthalmology Research (ARVO) 2023 Annual Meeting in New Orleans, Louisiana.
“Preclinical data presented today evaluate both tolerability within the target therapeutic range and aflibercept levels in Ixo-vec’s ongoing LUNA trial for the treatment of wet AMD. D., Chief Scientific Officer, Adverum Biotechnologies, said, “Additionally, approximately 10% of patients annually transition from unilateral to bilateral disease, warranting clinical evaluation of Ixo-vec.” We are encouraged by the results of a non-clinical study evaluating staggered bilateral dosing, as they represent an important area of unmet need: bilateral wet AMD.
Alternating bilateral administration of Ixo-vec in NHP was well tolerated and promoted therapeutic activity, with no signal of increased inflammation.
A No Adverse Effect Level (NOAEL) was identified for NHP at a human equivalent dose of 2E11 (3 X 10^10 vg/ocular dose for NHP) supporting human 2E11 and 6E10 doses in the ongoing Phase 2 LUNA trial. On Wet AMD.
Human-equivalent doses of both 2E11 and 6E10 resulted in therapeutic aflibercept levels comparable to the average peak levels observed in previous human studies utilizing NHP and higher doses of Ixo-vec.
A single intravitreal injection of Ixo-vec in the second eye resulted in peak aflibercept levels within the target therapeutic range.
Total antibody in the second eye was undetectable prior to injection of the Ixo-vec dose in the second eye, despite the elevated systemic humoral response after the first eye injection.
Presentations will be available on the Publications page of the Adverum website.
Gangnon RE, Lee KE, Klein BE, Iyengar SK, Sivakumaran TA, and Klein R (2015) Age-related macular degeneration severity in one eye and incidence and progression of age-related macular degeneration in the other eye: beaver dam. eye study. JAMA Ophthalmology; 133 (2): 125–132.
Rasmussen A., Fuchs J, Hansen LH, Larsen M, Sander B, and Lund-Andersen H (2017) Neovascular Age-Related Macular Degeneration: Is It Worth Treating Eyes with Low Vision? . eye 31, 978–980 (2017).
Wong TY, Lanzetta P, Bandello F, Eldem B, Navarro R, Lövestam-Adrian M, and Loewenstein A (2020) Current concepts and modalities for monitoring fellow eyes in neovascular age-related macular degeneration. Consensus of the expert panel. retina40, 599-611
Zarranz-Ventura J, Liew G, Johnston RL, Xing W, Akerele T, McKibbin M and others. (2014). Neovascular Age-Related Macular Degeneration Database: Report 2: Incidence, Management, and Visual Outcomes in Second-Treated Eyes. Ophthalmology; 121 (10): 1966–1975.
About exudative age-related macular degeneration
Wet AMD, also called neovascular AMD or nAMD, is a progressive form of AMD that affects approximately 10% of AMD patients. Wet AMD is the leading cause of blindness in people over the age of 65, with approximately 20 million people living with the condition worldwide. New cases of wet AMD are expected to increase significantly worldwide as the population ages. AMD is expected to affect 288 million people worldwide by 2040, with wet AMD accounting for about 10% of those cases. In addition, wet AMD is a bilateral disease, with an incidence of nAMD in the second eye of up to 42% during his first 2–3 years.
About Ixo-vec on Wet AMD
Advertisement is developing ixoberogene soroparvovec (Ixo-vec, formerly ADVM-022), a clinical-stage gene therapy product candidate for the treatment of wet AMD. Ixo-vec utilizes a proprietary vector capsid AAV.7m8 that carries the aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies (subretinal approaches) that require surgery to deliver gene therapy under the retina, Ixo-vec is administered as a one-time IVT injection in the doctor’s office. Designed to provide long-term efficacy, reduce the burden of frequent anti-vascular endothelial growth factor (VEGF) injections, optimize patient compliance, and improve visual outcomes in wet AMD patients . Recognizing the need for new treatment options for wet AMD, the US Food and Drug Administration has granted Fast Track designation to his Ixo-vec for the treatment of wet AMD. Ixo-vec has also received PRIME designation from the European Medicines Agency and an Innovation Passport from the UK’s Medicines and Healthcare Products Regulatory Agency for the treatment of wet AMD.
About LUNA study of Ixo-vec in Wet AMD
The LUNA trial is a double-mask, randomized Phase 2 trial conducted at approximately 40 sites in the United States and Europe. LUNA will evaluate her Ixo-vec in her 50+ year old wet AMD subjects who have shown response to anti-VEGF therapy. Up to 72 subjects will be randomized evenly between her previously assessed dose of 2E11 vg/eye and her new lower dose of 6E10 vg/eye. Four prophylactic steroid regimens will be studied with the aim of establishing a prophylactic corticosteroid regimen with minimal need for post-prophylaxis inflammation management. Prophylaxis regimens under evaluation include a 22-week taper regimen of topical difluprednate (Durezol®), a single dose of IVT dexamethasone (Ozurdex®), and a combination of topical Durezol® or IVT Ozurdex® with tapering for up to 10 weeks. It is included. Oral prednisone regimen. All four of LUNA’s prophylactic corticosteroid regimens cover the peak period of immunogenicity observed in preclinical and Phase 1 OPTIC trials.
The primary endpoints of the LUNA study were the mean change in best-corrected visual acuity (BCVA) from baseline to one year, and the incidence and severity of adverse events. Key secondary endpoints of LUNA included mean change in central subfield thickness (CST) from baseline to 1 year and assessment of efficacy of prophylactic corticosteroid regimens in minimizing inflammation. will be Additionally, LUNA will assess protein levels of aflibercept starting at his 14th week, with an interim analysis at 26th week. Study participants have the option to enroll in long-term follow-up studies.
About Adverum Biotechnologies
Adverum Biotechnologies (NASDAQ: ADVM) aims to establish gene therapy as a new standard of care for highly prevalent eye diseases, with the aim of developing functional therapies to restore vision and prevent blindness. It is a company in the clinical stage that we are aiming for. Adverum is designed to be delivered in the physician’s office to leverage the capabilities of a unique intravitreal (IVT) platform to eliminate the need for frequent ocular injections to treat these conditions. We are developing a long-lasting, single-dose regimen. Adverum is evaluating its new gene therapy candidates. ixoberogene soroparvovec (Ixo-vec, formerly called ADVM-022), as a one-time IVT injection for patients with neovascular or exudative age-related macular degeneration. By overcoming the challenges associated with current treatment paradigms for debilitating eye disease, Adverum aims to transform the standard of care, preserve vision and create profound societal impact around the world. For more information, please visit www.adverum.com.
Statements contained in this press release regarding possible future events or outcomes are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Design and enrollment of the ongoing LUNA trial evaluating alternating, bilateral, and 2×10^11 (2E11) doses and a new lower 6×10^10 (6E10) dose in the treatment of exudative AMD, and enhanced prophylaxis targeted corticosteroid regimen. Actual results may differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, but not limited to, the risks inherent in: regulatory uncertainty; registration uncertainty; early clinical trial results are not necessarily predictive of future clinical trials and results; Possible future complications or side effects associated with the use of Ixo-vec. Additional risks and uncertainties facing Adverum are set forth under the caption “Risk Factors” and also elsewhere in Adverum’s U.S. Securities and Exchange Commission (SEC) filings and reports. It is listed. SEC on March 30, 2023. Adverum undertakes no obligation to update such statements to reflect events or circumstances occurring after the date such statements were made.
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