Adverum Biotechnologies Announces Positive Preliminary Efficacy and Safety Data from LUNA Phase 2 Trial of Ixo-vec in Patients with Wet AMD

– Both dose levels (2E11 & 6E10) demonstrate potential best-in-class clinical activity in hard-to-treat patients including treatment burden reduction and maintenance of both visual acuity and anatomic endpoints –

– Preliminary safety data support a favorable benefit-risk profile at both dose levels –

– Ozurdex + difluprednate identified as potential “go-forward” prophylaxis –

– The vast majority of patients on the “go-forward” regimen had no inflammation and >90% of patients have no or minimal inflammation (0 or 0.5+ AC cells) –

– Preliminary efficacy and safety data trending similar to or better than the OPTIC study, in which patients continue to see on-going clinical benefit through at least 3 years –

– Webcast to be held today Thursday, February 8 at 8:00 a.m. EST –

REDWOOD CITY, Calif., Feb. 08, 2024 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company pioneering the use of gene therapy as a new standard of care for highly prevalent ocular diseases, today announced preliminary safety and efficacy data from the ongoing LUNA Phase 2 trial in patients with wet age-related macular degeneration (AMD). These data are being presented by Dr. Arshad Khanani today at the 47th Annual Meeting of the Macula Society. The presentation titled “Ixoberogene soroparvovec (Ixo-vec) Intravitreal Gene Therapy for Neovascular Age-Related Macular Degeneration: Preliminary Results from the LUNA Phase 2 Study" is scheduled for 10:56am ET.

“Wet AMD is a leading cause of blindness in people over the age of 65, requiring life-long anti-VEGF injections. Our goal with Ixo-vec is to provide patients virtually injection-free management of their wet AMD lasting years and potentially for life,” stated Laurent Fischer, M.D., president and chief executive officer of Adverum Biotechnologies. “We are pleased with the emerging treatment profile of Ixo-vec, showing potential for best-in-class efficacy and over 90% of subjects having no or minimal inflammation with our go-forward local prophylactic regimen. Underscoring the potential best-in-class profile of Ixo-vec, these early activity results were seen in hard-to-treat patients, who received over 9 annualized injections in the year prior to receiving Ixo-vec. Going into LUNA, we looked to replicate the robust clinical activity seen in OPTIC, in which patients continued to see clinical benefit through 3 years, with measured stable aflibercept through 4.5 years. We are proud to build upon our pioneering efforts with the most mature dataset and longest follow-up of all wet AMD intravitreal gene therapies currently in development.”

Dr. Fischer continued, “Going into LUNA, we also looked to establish that an enhanced prophylactic regimen combined with highly active doses of Ixo-vec would further enhance its long-term benefit-risk profile. With these early data, we are pleased with the promising profile of Ozurdex plus difluprednate which we expect to be our go-forward regimen. We look forward to sharing the maturing LUNA dataset with the goal of confirming the optimal dose(s) and prophylactic regimen for pivotal studies and with the plan to present our 26-week interim analysis in the middle of 2024.”

“Based on my experience as an investigator for over five years across multiple clinical trials with Ixo-vec for wet AMD, it’s promising to see the sustained disease control and a significant treatment burden reduction after a single intravitreal injection of Ixo-vec in previously treated patients with wet AMD,” said Arshad M Khanani, M.D., M.A., FASRS, Managing Partner and Director of Clinical Research at Sierra Eye Associates, Clinical Associate Professor at University of Nevada, Reno and Principal Investigator in LUNA trial. “Ixo-vec has the potential to shift the treatment paradigm for patients with wet AMD and I look forward to working with the Adverum team to advance Ixo-vec into pivotal studies.”

LUNA Trial Background and Baseline Demographics

The LUNA trial is an ongoing double-masked, randomized, Phase 2 trial. 60 patients with wet AMD were enrolled equally across two dose cohorts, 2E11 and 6E10 vg/eye. The study is designed to assess optimized prophylactic regimens, with patients receiving one and/or two locally administered corticosteroid regimens, with or without oral prednisone.

The LUNA trial builds on our experience with the OPTIC study, where landmark 2-year data was recently published in The Lancet’s eclinicalmedicine.

The data cut-off for these data is November 15, 2023, except for treatment burden reduction, which is of January 2, 2024.

LUNA Preliminary Efficacy and Safety Data Summary

Both the 2E11 and 6E10 doses demonstrated maintenance of visual and anatomic outcomes. Notably, both doses resulted in a potentially best-in-class reduction in annualized anti-vascular endothelial growth factor (VEGF) injections and the percentage of patients remaining free of annualized injections, with data trending similar to or better than the OPTIC study.

• Treatment Burden Reduction
  
  • At 26 weeks, Ixo-vec demonstrated annualized reduction in anti-VEGF injection rates of 90% (n=19) at 6E10 and 94% (n=20) at 2E11.
  • At 26 weeks, Ixo-vec demonstrated injection free rates of 68% (n=19) at 6E10 and 85% (n=20) at 2E11.
• Visual (BCVA) and Anatomic (CST) Outcomes:
  
  • Visual acuity was maintained at both dose levels - mean BCVA change from baseline to last visit (95% CI):
    
    • 2E11: -1.7 (-4.5, 1.2)
    • 6E10: +0.5 (-2.2, 3.3)
  • Anatomic endpoints were maintained at both dose levels - mean CST (μm) change from baseline to last visit (95% CI):
    
    • 2E11: -16.4 (-31.5, -1.3)
    • 6E10: -7.9 (-30.9, 15.0)
    • In a sub-group analysis of patients with higher baseline CST, a greater reduction in CST was demonstrated, indicating the robust efficacy potential of Ixo-vec gene therapy.
• Safety
  
  • Preliminary data suggest corticosteroid prophylaxis optimization at both the 2E11 and 6E10 doses appears to result in improved inflammatory profiles in LUNA as compared to OPTIC study results.
  • Ixo-vec was generally well-tolerated, and when present intraocular inflammation was responsive to local corticosteroids.
  • No Ixo-vec related serious adverse events were reported.
  • No episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion or hypotony were reported.
  • Preliminary data indicate that select prophylactic regimens are outperforming others that do not provide sustained prophylaxis.
    
    • Early on in the study, the company implemented a protocol amendment to augment the Ozurdex containing regimens with a course of Durezol eye drops.
    • Preliminary data indicate that the amended Ozurdex + Durezol regimen may be the favorable prophylactic regimen for future pivotal studies.
    • In this potential “go-forward” regimen, the vast majority of patients had no inflammation, with over 90% of these patients having no or minimal inflammation. Oral corticosteroids showed no incremental benefit.

Upcoming Ixo-vec Milestones

• LUNA 26-week interim analysis expected mid-2024
• Continued FDA and EMA formal and informal regulatory interactions
• Initiation of Phase 3 trial expected H1’25
  

Webcast Details

The live webcast will be accessible under Events and Presentations in the Investors section of the company's website. Listeners can register for the webcast via this webcast link. Analysts wishing to participate in the question and answer session should use this dial-in link. A replay of the webcast will be available on the company’s website shortly after the conclusion of the webcast.

About Wet Age-Related Macular Degeneration

Wet AMD, also known as neovascular AMD or nAMD, is a VEGF driven advanced form of AMD affecting approximately 10% of patients living with AMD associated with the build-up of fluid in the macula and the retina. 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. The current standard of care requires frequent life-long repeated bolus injections of anti-VEGF in the eye. IVT gene therapy has the promise to preserve vision and reduce most or all injections for the life of the patient by delivering stable therapeutic levels of anti-VEGF to control macular fluid.

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-VEGF, optimize patient compliance and improve vision outcomes for patients with wet AMD. In recognition of the need for new treatment options for wet AMD, FDA granted Fast Track designation for Ixo-vec for the treatment of wet AMD. Ixo-vec has also received PRIME designation from the EMA and the Innovation Passport from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency for the treatment of wet AMD.

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. Additionally, 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 of Ixo-vec as a one-time IVT injection for the treatment of wet AMD, including its potential to improve vision outcomes, the potential best-in-class efficacy of Ixo-vec, and anticipated timing of preliminary and interim data from the Phase 2 LUNA trial and initiation of a Phase 3 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 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 September 30, 2023 filed with the SEC on November 9, 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, except as required by law.

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