Adverum Biotechnologies Presents Nonclinical Data at the 2023 ARVO Annual Meeting Supporting Potential for Staggered Bilateral Administration of Ixo-vec

Rhea-AI Summary

Adverum Biotechnologies announced new nonclinical data supporting its Phase 2 LUNA trial of Ixo-vec for treating wet age-related macular degeneration (wet AMD). The data suggest that staggered bilateral administration of Ixo-vec is feasible, with promising tolerability and aflibercept levels within therapeutic ranges. The study identified a no-observed-adverse-effect level (NOAEL) at a human equivalent dose of 2E11, reinforcing the ongoing evaluation of both 2E11 and 6E10 doses. Approximately 10% of wet AMD patients convert to bilateral disease annually, highlighting the treatment's unmet need. These findings were presented at the ARVO 2023 Annual Meeting, further emphasizing Ixo-vec's potential to improve patient outcomes in a condition that affects around 20 million people globally.

Positive

• Nonclinical data support tolerability and therapeutic levels of Ixo-vec in wet AMD treatment.
• NOAEL identified at human equivalent dose of 2E11, supporting ongoing Phase 2 LUNA trial doses.
• Feasibility of staggered bilateral administration demonstrated in non-human primates.

Negative

• None.

- Wet age-related macular degeneration (wet AMD) is a bilateral disease and incidence of neovascularization (nAMD) in the second eye is up to 42% in the first two to three years following diagnosis in the primary eye -

- Staggered administration of Ixo-vec in non-human primates (NHPs) showed peak aflibercept protein levels in the second eye within the targeted therapeutic range, supporting the potential for bilateral administration -

- A no-observed-adverse-effect-level (NOAEL) in NHPs was identified at the human equivalent dose of 2x10^11 vg/eye (2E11), supporting the 2E11 dose and the 6x10^10 vg/eye (6E10) dose 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), a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases, today announced nonclinical data supporting the two doses of ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022) being evaluated in the Phase 2 LUNA trial and the potential for staggered, bilateral administration in the treatment of wet AMD. The data were featured in an oral presentation at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting in New Orleans, Louisiana.

“The nonclinical data presented today support the two doses we are evaluating in the ongoing LUNA trial of Ixo-vec for the treatment of wet AMD, both in terms of tolerability and aflibercept levels within the targeted therapeutic range,” said Brigit Riley, Ph.D., chief scientific officer at Adverum Biotechnologies. “Additionally, we are encouraged by the results of our nonclinical study evaluating staggered, bilateral administration as approximately 10% of patients convert from single eye to bilateral disease per year, representing an important area of unmet need that warrants clinical evaluation of Ixo-vec in bilateral wet AMD.”

Data Highlights

• Staggered, bilateral administration of Ixo-vec in NHPs was well tolerated with encouraging therapeutic activity and no signals of increased inflammation.
• A no-observed-adverse-effect level (NOAEL) was identified in NHPs at the human equivalent dose of 2E11 (3 X 10^10 vg/eye dose in NHP) supporting the human 2E11 and 6E10 doses in the ongoing Phase 2 LUNA study in wet AMD.
• Both 2E11 and 6E10 human equivalent doses resulted in therapeutic aflibercept levels with mean peak levels comparable with those observed in previous NHP and in human studies utilizing higher doses of Ixo-vec.
• Administration of a single intravitreal dose of Ixo-vec in the second eye resulted in peak aflibercept levels that are within the targeted therapeutic range.
• Despite elevated systemic humoral response after first eye injection, second eye total antibodies were undetectable prior to injection of Ixo-vec dose in the second eye.
  

The presentation will be made available on the Publications page of the Adverum website.

Reference:

Gangnon RE, Lee KE, Klein BE, Iyengar SK, Sivakumaran TA and Klein R (2015) Severity of age-related macular degeneration in 1 eye and the incidence and progression of age-related macular degeneration in the fellow eye: the Beaver Dam Eye Study. JAMA Ophthalmol; 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 worthwhile treating an eye with poor visual acuity, if the visual acuity of the fellow eye is good?. 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 the fellow eye in neovascular age-related macular degeneration. An Expert Panel Consensus. Retina. 40, 599-611

Zarranz-Ventura J, Liew G, Johnston RL, Xing W, Akerele T, McKibbin M et al. (2014). The neovascular age-related macular degeneration database: report 2: incidence, management, and visual outcomes of second treated eyes. Ophthalmology; 121 (10): 1966–1975.

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 people over 65 years of age, with approximately 20 million individuals worldwide living with this condition. New cases of wet AMD are 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. Additionally, wet AMD is a bilateral disease and incidence of nAMD in the second eye is up to 42% in the first two to three years.

About Ixo-vec in Wet AMD
Adverum is developing ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), its clinical-stage gene therapy product candidate, 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 is designed to be administered as a one-time IVT injection in the physician’s office, deliver long-term efficacy, reduce the burden of frequent anti-vascular endothelial growth factor (VEGF) injections, optimize patient compliance and improve vision outcomes for patients with wet AMD. In recognition of the need for new treatment options for wet AMD, the U.S. Food and Drug Administration granted Fast Track designation for Ixo-vec for the treatment of wet AMD. Ixo-vec also received PRIME designation from the European Medicines Agency and the Innovation Passport from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency for the treatment of wet AMD.

About LUNA Trial of Ixo-vec in Wet AMD
The LUNA trial is a double-masked, randomized, Phase 2 trial being conducted at approximately 40 sites in the U.S. and Europe. LUNA will evaluate Ixo-vec in subjects with wet AMD who are 50 years or older and have demonstrated a response to anti-VEGF treatment. Up to 72 subjects will be randomized equally between the previously evaluated 2E11 vg/eye dose and a new, lower 6E10 vg/eye dose. Four prophylactic steroid regimens will be studied with the aim of establishing a prophylactic corticosteroid regimen with minimal need for inflammation management post prophylaxis. Prophylactic regimens being evaluated include 22 weeks of a tapered regimen of topical difluprednate (Durezol®), a single administration of IVT dexamethasone (Ozurdex®), and a combination of either topical Durezol® or IVT Ozurdex® with up to 10 weeks of a tapered regimen of oral prednisone. All four prophylactic corticosteroid regimens in LUNA cover the period of peak immunogenicity observed in non-clinical studies and in the Phase 1 OPTIC study.

The LUNA trial primary endpoints are mean change in best corrected visual acuity (BCVA) from baseline to one year, as well as the incidence and severity of adverse events. Important secondary endpoints in LUNA include the mean change in central subfield thickness (CST) from baseline to one year and assessing the effectiveness of prophylactic corticosteroid regimens on minimizing inflammation. Additionally, LUNA will assess aflibercept protein levels starting at Week 14 and include an interim analysis at Week 26. Study participants will have the option to enroll in a long-term extension study.

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 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 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 for staggered, bilateral administration in the treatment of wet AMD, as well as the design of and patient enrollment in the ongoing LUNA trial evaluating the 2x10^11 (2E11) dose and a new, lower 6x10^10 (6E10) dose, along with enhanced prophylactic corticosteroid 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 Annual Report on Form 10-K for the year ended December 31, 2022 filed with the SEC on March 30, 2023. 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.

Corporate, Investor and Media Inquiries
Anand Reddi
Vice President, Head of Corporate Strategy, External Affairs and Engagement
Adverum Biotechnologies, Inc.
T: 650-649-1358
E: areddi@adverum.com 

FAQ

What are the new findings from Adverum Biotechnologies regarding Ixo-vec for wet AMD?

Adverum's new findings indicate that Ixo-vec shows good tolerability and maintains therapeutic aflibercept levels, supporting its Phase 2 LUNA trial for wet AMD.

What is the NOAEL identified for Ixo-vec in nonclinical studies?

The NOAEL for Ixo-vec was identified at a human equivalent dose of 2E11, which validates its safety for ongoing trials.

What is the purpose of the Phase 2 LUNA trial for Ixo-vec?

The Phase 2 LUNA trial aims to evaluate the efficacy and safety of Ixo-vec in treating patients with wet AMD who have responded to anti-VEGF treatment.

How significant is the issue of bilateral wet AMD in patients?

The significance lies in the fact that approximately 10% of wet AMD patients convert to bilateral disease each year, indicating a substantial unmet medical need.

When was the new data regarding Ixo-vec presented?

The new data was presented at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting.