A phase 3 study will evaluate the safety and efficacy of Ixo-vec (Adverum Biotechnologies), a one-time intravitreal (IVT) injection for patients with neovascular age-related macular degeneration (wet-AMD).
The US-based ARTEMIS Phase 3 study will evaluate a single administration of Ixo-vec (6E10 vg/eye) compared to aflibercept (2mg) every eight weeks in approximately 284 patients with wet AMD. With both treatment-naïve and previously treated patients, the study is intended to address a patient population that is representative of the real world, including those with the highest treatment burden.
Ixo-vec’s potential to dramatically reduce treatment burden, provide lifelong injection freedom and enhance long-term vision outcomes could deliver a compelling benefit
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.
Following US Food and Drug Administration (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.
Global Study to Follow
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.
Previous studies – OPTIC and LUNA – have demonstrated the ability for Ixo-vec “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”, according to said Dr Carl Danzig, Rand Eye Institute and an investigator for ARTEMIS.
Dr Dante Pieramici, Medical Director of Research, California Retina Consultants and an investigator for ARTEMIS observed that Ixo-vec could be a solution to the “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 two 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,” Dr Pieramici said.
“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.”
Emulating the Real World
Dr Sean Adrean, Partner, Retina Consultants of Orange County and an investigator for ARTEMIS explained the significance of enrolling both treatment-naive and treatment-experienced patients in this Phase 3 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. 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.”
