High-level results from AstraZeneca’s Cardiac Amyloid Reaching for Extended Survival (CARES) Phase III clinical program showed that anselamimab, a light chain depleter antibody, did not achieve statistical significance for the primary endpoint compared to placebo in patients with Mayo stages IIIa and IIIb light chain (AL) amyloidosis. The primary endpoint was defined as a hierarchical combination of time to all-cause mortality (ACM) and frequency of cardiovascular hospitalizations (CVH). All patients in the clinical program received background standard of care for plasma cell dyscrasia.
Anselamimab showed highly clinically meaningful improvement in time to ACM and frequency of CVH in a prespecified subgroup of patients, compared to placebo.
AL amyloidosis is a rare, systemic and progressive disorder caused by defective plasma cells in the bone marrow. In AL amyloidosis, abnormal light chain proteins produced by these plasma cells misfold, aggregate and form amyloid fibrils that deposit in tissues and organs. Left untreated, the accumulation of these toxic amyloid deposits, particularly in the heart and kidneys, can cause progressive organ damage and dysfunction and may lead to premature death, most commonly due to cardiac failure.
Ashutosh Wechalekar, MBBS, MD, FRCP, FRCPath, DM, Consultant Haematologist at University College London Hospitals NHS Foundation Trust (UCLH), Professor of Medicine and Haematology at University College London (UCL) and lead principal investigator of the program, said: “While the study did not meet the primary endpoint in the overall patient population, results from a pre-defined subgroup suggest that anselamimab, by targeting and clearing amyloid deposits, may address a leading cause of organ damage and functional impairment in these patients. The potential to extend survival and reduce cardiovascular hospitalizations would represent a practice-changing advancement for this patient group.”
Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare Disease, said: “Alexion is pioneering a novel mechanism of action to address organ damage from existing amyloid deposits in patients with AL amyloidosis, a devastating disease often diagnosed in advanced stages with poor prognosis. Anselamimab is the first and only investigational fibril depleter to show clinical benefit in AL amyloidosis, and these results underscore its potential to address a critical treatment gap in a prespecified subgroup of patients.”
Anselamimab was well tolerated, with the majority of events balanced between the anselamimab treatment arm and the placebo arm.
Evaluation of full results is ongoing to further characterize the efficacy and safety of anselamimab. Alexion plans to share these data with global health authorities and present them at a forthcoming medical meeting.
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