The global CARES phase 3 clinical programme has shown that treatment with anselamimab, a potential first-in-class anti-fibril therapy, resulted in nominally statistically significant and highly clinically meaningful benefit in adults with advanced kappa light chain (AL) amyloidosis as first-line therapy added to standard of care Plasma Cell Dyscrasia (PCD) treatments, compared to placebo. In the overall population of patients with AL amyloidosis, treatment with anselamimab did not meet the primary endpoint, defined as a hierarchical combination of time to All-Cause Mortality (ACM) and frequency of cardiovascular hospitalisations (CVH), as previously disclosed.

In a prespecified subgroup analysis of patients with kappa predominant light chain isotype, anselamimab improved survival by 62 percent, measured by ACM (hazard ratio 0.38; 95 confidence interval [CI] 0.17, 0.86; nominal p=0.012), and reduced the frequency of CVH by 71 percent (incidence risk ratio 0.29; 95 percent CI 0.10, 0.87; nominal p=0.028), compared to placebo in the subgroup with kappa AL amyloidosis.

The reduction in the risk of ACM in the kappa subgroup was also observed in both trials comprising the CARES phase 3 clinical programme among patients with kappa isotype with Mayo stage 3a disease (75 perecent) and Mayo stage 3b disease (48 percent). No differences in ACM and CVH were observed among patients with lambda predominant light chain isotype.

At 50 weeks, numerical improvements favoring anselamimab were observed in key secondary endpoints, including quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire-Overall Score (Hodges-Lehmann median difference [HLMD]: 10.37 [95 percent CI -9.38, 25.56; p=0.113), and functional capacity, as measured by the Six-Minute Walk Test ([HLMD]: 18.00 [95 percent CI -71.60, 95.92; p=0.145), in patients with kappa light chain amyloidosis who received anselamimab, 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, FRCP, FRCPath, DM, Honorary Consultant Haematologist at University College London Hospitals and Professor of Medicine and Haematology, University College London, and lead principal investigator of the programme, said, “People living with advanced AL amyloidosis often face persistent, progressive and debilitating organ damage with no available options to target and clear existing amyloid fibril deposits. Results from the CARES Phase 3 programme show that anselamimab, a monoclonal antibody with a novel mechanism of action designed to target and remove amyloid fibrils, improved survival and reduced the frequency of cardiovascular hospitalisations in patients with kappa light chain amyloidosis. Anselamimab has the potential to offer a novel, clinically meaningful therapeutic for this subgroup of patients with kappa AL amyloidosis who can be easily identified by simple, routinely-used diagnostics.”

Worldwide, there are an estimated 74,000 patients living with AL amyloidosis, approximately 20 percent of whom have kappa light chain amyloidosis and approximately 80 percent of whom have lambda light chain amyloidosis.

Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety, Alexion, AstraZeneca Rare Disease, said, “The CARES phase 3 programme is the first to show that targeting existing deposits of amyloid fibrils could deliver clinically meaningful survival and cardiovascular benefit in adults with kappa light chain amyloidosis, underscoring anselamimab's potential as a first-line therapy on top of standard of care. With anselamimab and our leading amyloidosis portfolio, we are advancing pioneering science with the goal of addressing critical treatment gaps. We look forward to continued engagement with health authorities to advance this potential first-in-class anti-fibril therapy.”