Adverum Biotechnologies has launched ARTEMIS, a pioneering Phase 3 clinical trial evaluating Ixo-vec (ixoberogene soroparvovec) as a potential one-time gene therapy solution for patients with wet age-related macular degeneration (AMD). This milestone marks the first-ever registrational trial of an intravitreal gene therapy in wet AMD patients.
The U.S.-based study will enroll approximately 284 participants, encompassing both treatment-naïve and previously treated patients. The trial will compare a single administration of Ixo-vec (6E10 vg/eye) against the current standard of care, aflibercept (2mg) given every eight weeks.
Trial Design and Endpoints
The ARTEMIS study employs a randomized, double-masked, sham-controlled design with two treatment arms. Following FDA guidance, all participants will receive three initial loading doses of aflibercept before randomization. The primary endpoint measures the mean change in best corrected visual acuity (BCVA) at one year, with a non-inferiority margin of -4.5 letters. Patients in both arms will have access to supplemental aflibercept injections and prophylactic steroid eye drops as needed.
Addressing Critical Unmet Needs
Recent data has revealed a concerning trend: up to 42% of wet AMD patients discontinue treatment after two years, leading to poor long-term vision outcomes. Dr. Dante Pieramici, Medical Director of Research at California Retina Consultants and ARTEMIS investigator, emphasized the significant unmet need for longer-acting anti-VEGF therapies.
"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," stated Dr. Pieramici.
Innovation in Treatment Approach
Laurent Fischer, M.D., president and chief executive officer of Adverum Biotechnologies, highlighted the transformative potential of their approach: "Gene therapy is recognized as the most exciting modality on the horizon for the treatment of wet AMD. With over 4 years of experience, we 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."
Real-World Impact and Patient Population
The trial's inclusive design, incorporating both treatment-naïve and previously treated patients, aims to generate data representative of real-world patient demographics. Dr. Sean Adrean, Partner at Retina Consultants of Orange County and trial investigator, noted that this approach will help answer key questions about Ixo-vec's performance in patients with high injection burdens who would most benefit from gene therapy.
Disease Burden and Market Impact
Wet AMD affects approximately 20 million individuals worldwide and is a leading cause of blindness in people over 65. The condition is expected to grow significantly, with AMD projected to impact 288 million people globally by 2040. The bilateral nature of the disease, with up to 42% of patients developing it in their second eye within two to three years, underscores the importance of developing effective, long-term treatments.
Regulatory Status and Future Plans
Ixo-vec has received multiple regulatory designations, including Fast Track and Regenerative Medicine Advanced Therapy (RMAT) designations from the FDA, PRIME designation from the EMA, and the Innovation Passport from the UK's Medicines and Healthcare Products Regulatory Agency. ARTEMIS is the first of two planned Phase 3 registrational trials, with details on the second study, AQUARIUS, to be announced in the future.
