AstraZeneca’s Anselamimab Phase III Trial Falls Short on Primary Endpoint, Shows Promise in Subgroup

High-level results from the Phase III CARES clinical program indicate that anselamimab, an antibody designed to deplete light chains in AL amyloidosis, did not meet the primary endpoint in patients with advanced (Mayo stages IIIa and IIIb) disease. The primary measure was a combination of time to all-cause mortality and the rate of cardiovascular hospitalizations. All patients in the study were also treated with standard therapies for plasma cell dyscrasia.

“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,” said,Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare Disease. 

Despite not reaching statistical significance overall, anselamimab showed substantial clinical benefit in a predefined subgroup, demonstrating improved survival and fewer cardiovascular hospitalizations compared to placebo. The treatment was generally well tolerated, with adverse events evenly distributed across both treatment and control groups.

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 programme, 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 hospitalisations would represent a practice-changing advancement for this patient group.”

AL amyloidosis is a rare condition where misfolded light chain proteins form harmful deposits in vital organs, especially the heart and kidneys, leading to serious complications and high mortality if untreated. Full data analysis from the CARES program is ongoing to better understand anselamimab’s safety and potential benefits across different patient populations.