Adverum Biotechnologies Initiates ARTEMIS Phase 3 Study Evaluating Ixo-vec for Wet AMD

Rhea-AI Summary

Adverum Biotechnologies (Nasdaq: ADVM) has initiated ARTEMIS, a pioneering Phase 3 study evaluating Ixo-vec, a one-time gene therapy for wet AMD. The US-based trial will assess a single Ixo-vec injection versus aflibercept in 284 patients, including both treatment-naïve and previously treated individuals.

The study's primary endpoint measures change in best corrected visual acuity at one year, with a non-inferiority margin of -4.5 letters. ARTEMIS is the first of two planned Phase 3 registrational trials, with the second study (AQUARIUS) to be conducted globally.

Key trial design features include:

• Single administration of Ixo-vec (6E10 vg/eye) compared to aflibercept (2mg) every 8 weeks
• Three loading doses of aflibercept prior to Ixo-vec administration
• Eligibility for supplemental aflibercept injections
• Prophylactic steroid eye drops for all patients

Positive

• First-ever registrational intravitreal gene therapy trial in wet AMD
• Broad patient inclusion criteria enhancing commercial potential
• Addresses 42% treatment discontinuation rate in current therapies
• Potential for lifelong treatment with single injection

Negative

• Non-inferiority trial design vs. superiority
• Requires three loading doses of aflibercept before treatment
• Supplemental aflibercept injections may still be needed
• Second Phase 3 trial (AQUARIUS) details not yet disclosed

Insights

Ophthalmology Clinical Development Expert

Adverum's initiation of the ARTEMIS Phase 3 trial for Ixo-vec represents a significant clinical milestone in wet AMD treatment development. This trial marks the first-ever registrational intravitreal gene therapy study in wet AMD, positioning Adverum at the forefront of potentially transformative treatment options.

The trial design is particularly strong, evaluating 284 patients with wet AMD in both treatment-naïve and previously treated populations - a comprehensive approach that should accelerate enrollment and generate data applicable to real-world clinical practice. The primary endpoint of non-inferiority in vision improvement at one year (with a margin of -4.5 letters) against aflibercept sets a reasonable efficacy bar.

What's compelling about Ixo-vec is its potential to address a critical unmet need: up to 42% of patients discontinue wet AMD treatment after 2 years due to injection burden. A one-time gene therapy could dramatically improve treatment adherence and long-term outcomes. The ability to include aflibercept supplemental therapy if needed also provides a safety net for patients.

This represents the first of two planned Phase 3 studies, with the global AQUARIUS trial to follow. While positive, investors should recognize that even with successful trials, regulatory approval remains distant with typical timelines suggesting potential market entry no earlier than 2027-2028.

Biotechnology Investment Analyst

The ARTEMIS Phase 3 initiation meaningfully derisks Adverum's lead asset development program and represents significant execution against corporate objectives. For a $91.5 million market cap company, advancing to Phase 3 with a potential first-in-class therapy for wet AMD - a multibillion-dollar market - creates substantial value inflection potential.

Particularly noteworthy is the trial's inclusion of both treatment-naïve and previously treated patients, effectively broadening the potential label and commercial opportunity if approved. The non-inferiority design against aflibercept (standard of care) with a reasonable -4.5 letter margin strikes an appropriate balance between feasibility and clinical relevance.

Investors should recognize both opportunities and challenges: While a one-time gene therapy could dramatically reduce treatment burden compared to current bimonthly/quarterly injections, the Phase 3 program will be capital-intensive. With Adverum's current market capitalization, additional financing will likely be necessary to fund both planned registrational trials (ARTEMIS and AQUARIUS).

The significance of being first to initiate a registrational gene therapy study in wet AMD cannot be overstated. This creates potential first-mover advantage in what could become a paradigm-shifting approach to treating a condition affecting millions globally, representing a genuine milestone that advances Adverum's commercial prospects.

• Ixo-vec is a potential best-in-class one-time gene therapy designed to deliver long-term efficacy, reduce the burden of frequent anti-VEGF and improve vision outcomes for patients with wet AMD
• ARTEMIS is the first-ever initiation of a registrational intravitreal gene therapy trial in patients with wet AMD
• Non-inferiority study to evaluate a single Ixo-vec injection compared to on-label aflibercept 2mg in both treatment-naïve and previously treated patients
  

REDWOOD CITY, Calif., March 03, 2025 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company pioneering the use of gene therapy to preserve sight for life in highly prevalent ocular diseases, today announced the initiation of the ARTEMIS Phase 3 study. This pivotal trial is designed to evaluate the efficacy and safety of Ixo-vec (ixoberogene soroparvovec) as a one-time intravitreal (IVT) injection for patients with neovascular (wet) age-related macular degeneration (AMD).

ARTEMIS is a US-based study evaluating a single administration of Ixo-vec (6E10 vg/eye) compared to aflibercept (2mg) every 8 weeks in approximately 284 patients with wet AMD, including both treatment-naïve and previously treated patients. The primary endpoint is mean change from baseline in best corrected visual acuity (BCVA) at one year (average of weeks 52 and 56) with a non-inferiority (NI) margin of -4.5 letters. Per FDA guidance, all patients will receive three loading doses of aflibercept prior to receiving Ixo-vec. Patients in both arms will be eligible for supplemental injections of aflibercept and will receive prophylactic steroid eye drops.  

ARTEMIS is the first of two planned Phase 3 registrational trials to evaluate Ixo-vec in patients with wet AMD. Details on the second study, named AQUARIUS and to be conducted globally, will be forthcoming.

“Gene therapy is recognized as the most exciting modality on the horizon for the treatment of wet AMD. Initiation of the Phase 3 ARTEMIS trial demonstrates our commitment to transforming the landscape with a one-time IVT injection to help restore vision and prevent blindness,” stated Laurent Fischer, M.D., president and chief executive officer of Adverum Biotechnologies. “With over 4 years of experience, we are at the forefront and believe Ixo-vec is positioned as a best-in-class therapy to provide potentially lifelong benefit to patients who depend on frequent injections to preserve their sight. Huge kudos to my colleagues at Adverum who have worked expeditiously to initiate ARTEMIS, a pioneering effort, and who have consistently outperformed our ambitious timelines.”

“Leveraging our robust data for Ixo-vec, the ARTEMIS Phase 3 trial was designed to enhance the potential for clinical, regulatory and commercial success,” stated Rabia Gurses Ozden, MD, Chief Medical Officer at Adverum. “We have been thrilled by the enthusiasm of retina specialists for this design, including studying Ixo-vec in both treatment-naïve and previously treated patients, which we expect will increase the speed of enrollment and generate a registrational dataset representative of real-world patient demographics. We are eager to generate the data necessary to seek regulatory approval and ultimately establish Ixo-vec as a transformative treatment option for a broad spectrum of wet AMD patients.”

“There continues to be tremendous unmet need for longer-acting anti-VEGF therapies. Underscoring the unmet need, recent data indicate that up to 42% of patients stop treatment for wet AMD after 2 years, which results in poor long-term vision outcomes. Ixo-vec’s potential to dramatically reduce treatment burden, provide lifelong injection freedom and enhance long-term vision outcomes could deliver a compelling benefit for a large proportion of wet AMD patients,” said Dr. Dante Pieramici, Medical Director of Research, California Retina Consultants and an investigator for ARTEMIS. “Consistent with the strong patient preference for Ixo-vec indicated by LUNA patients, there is great interest from my patients when they hear about a therapy like Ixo-vec that has the potential to treat their disease with a single injection. I’m delighted to have served as an investigator for both OPTIC and LUNA, and I look forward to working with the Adverum team on the ARTEMIS pivotal study.”

“When designing registrational trials for patients with wet AMD, it’s not always feasible to study the therapeutic agent in a patient population that closely represents the real-world. Adverum’s inclusion in ARTEMIS of both treatment-naive and treatment-experienced patients is intended to address a broad patient population, including those with the highest treatment burden,” said Dr. Sean Adrean, Partner, Retina Consultants of Orange County and an investigator for ARTEMIS. “Based on its design, I expect the data coming out of the ARTEMIS trial will be highly informative and answer the key question of how Ixo-vec is expected to perform in those patients with high injection burdens and would most benefit from gene therapy. Looking back over 2 years ago, it was a pleasure to kick-off enrollment in LUNA, Ixo-vec's Phase 2 clinical trial, and be part of that successful trial.  Now today, it’s a thrill to be one of the first sites to begin screening patients and contribute to Ixo-vec's Phase 3 clinical trial.”

“Delivering continuous levels of aflibercept to reduce treatment burden and improve visual outcomes may be even more profound in treatment naïve patients,” said Dr. Carl Danzig, Rand Eye Institute and an investigator for ARTEMIS. “In OPTIC and LUNA, Ixo-vec has demonstrated the ability to durably produce therapeutic levels of aflibercept with an acceptable long-term safety profile, suggesting a potential lifelong benefit with a therapy that is well tolerated. It’s a great pleasure to be a part of this registrational program, and I look forward to working with the Adverum team to generate data to more fully elucidate Ixo-vec’s therapeutical potential for my patients.”

About the ARTEMIS Phase 3 Study

The Phase 3 ARTEMIS trial (NCT06856577) is designed to evaluate the safety and efficacy of Ixo-vec in a randomized (1:1), double-masked, sham-controlled, two-arm study. The US-based trial is intended to randomize approximately 284 patients, including both patients who are treatment naïve and patients who have been previously treated.

The primary endpoint, measured at an average of weeks 52 and 56, is NI in mean BCVA change from baseline with a NI margin of -4.5 letters. The key secondary endpoint is reduction of injection burden as measured by mean number of injections received. All patients will receive three monthly loading doses of aflibercept prior to receiving Ixo-vec. Patients in both arms will be eligible for supplemental injections of aflibercept and will receive topical steroid eye drops.

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 and Regenerative Medicine Advanced Therapy (RMAT) designations 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 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 long-term potential best-in-class product profile of Ixo-vec; potential benefits of Ixo-vec, including potential life-long benefits; the trial design of the Ixo-vec Phase 3 pivotal program and the planned initiation of a second Phase 3 registrational trial; the potential of Ixo-vec to be transformative and a best-in-class therapy; the potential of Ixo-vec to shift the treatment paradigm for patients with wet AMD; the ability to establish gene therapy as a standard of care for wet AMD patients; and other statements that are not a historical fact. 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; the potential for future complications or side effects in connection with use of Ixo-vec; and risks associated with market condition. 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, 2024 filed with the SEC on November 4, 2024 and subsequent filings with the SEC. 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.

Inquiries:

Adverum Investor Relations

Email: ir@adverum.com

FAQ

What is the primary endpoint of ADVM's ARTEMIS Phase 3 trial for Ixo-vec?

The primary endpoint is mean change from baseline in best corrected visual acuity (BCVA) at one year, with a non-inferiority margin of -4.5 letters.

How many patients will be enrolled in ADVM's ARTEMIS Phase 3 study?

The ARTEMIS study will enroll approximately 284 patients with wet AMD, including both treatment-naïve and previously treated patients.

What is the dosing regimen for Ixo-vec in ADVM's Phase 3 ARTEMIS trial?

Patients will receive a single administration of Ixo-vec (6E10 vg/eye) after three loading doses of aflibercept, with eligibility for supplemental aflibercept injections.

How does ADVM's Ixo-vec aim to address the treatment burden in wet AMD?

Ixo-vec is designed as a one-time intravitreal injection to provide potentially lifelong benefit, reducing the need for frequent anti-VEGF injections that currently lead to 42% treatment discontinuation after 2 years.