AstraZeneca reported that the global CARES Phase 3 clinical program of anselamimab, a potential first‑in‑class anti‑fibril therapy for light chain (AL) amyloidosis, did not meet its primary endpoint in the overall study population but showed notable benefits in a prespecified subgroup with kappa light chain disease. The primary endpoint—a hierarchical combination of time to all‑cause mortality (ACM) and frequency of cardiovascular hospitalizations (CVH)—was not achieved when all AL amyloidosis patients were analyzed together, as previously disclosed.
Despite the overall miss, treatment with anselamimab added to standard plasma cell dyscrasia therapy produced nominally statistically significant and clinically meaningful benefit in adults with advanced kappa AL amyloidosis. In this prespecified kappa‑predominant subgroup, anselamimab improved survival by 62%, with a hazard ratio for all‑cause mortality of 0.38 (95% CI 0.17–0.86; nominal p=0.012), compared with placebo. The drug also reduced the frequency of cardiovascular hospitalizations by 71%, with an incidence risk ratio of 0.29 (95% CI 0.10–0.87; nominal p=0.028).
The reduction in mortality risk for kappa patients was seen in both CARES trials among those with Mayo stage IIIa disease (75% risk reduction) and Mayo stage IIIb disease (48% risk reduction). No differences in all‑cause mortality or cardiovascular hospitalizations were observed in patients with lambda‑predominant light chain isotype. At 50 weeks, numerical trends favoring anselamimab were also seen in key secondary endpoints in the kappa subgroup, including quality of life measured by the Kansas City Cardiomyopathy Questionnaire‑Overall Score (Hodges‑Lehmann median difference 10.37; 95% CI −9.38 to 25.56; p=0.113) and functional capacity by the Six‑Minute Walk Test (Hodges‑Lehmann median difference 18.00; 95% CI −71.60 to 95.92; p=0.145), though these did not reach statistical significance.
AL amyloidosis is a rare, progressive systemic disorder caused by defective plasma cells in the bone marrow that produce abnormal light chain proteins. These proteins misfold, aggregate and form amyloid fibrils that deposit in organs such as the heart and kidneys, leading to progressive damage and potentially premature death, most often from cardiac failure if left untreated. An estimated 74,000 people worldwide are living with AL amyloidosis, about 20% with kappa and about 80% with lambda light chain disease.
Lead principal investigator Ashutosh Wechalekar, FRCP, FRCPath, DM, said patients with advanced AL amyloidosis often experience persistent organ damage with no options to clear existing amyloid fibril deposits. He noted that CARES results show anselamimab, a monoclonal antibody designed to target and remove amyloid fibrils, improved survival and reduced cardiovascular hospitalizations in kappa AL amyloidosis, and has potential as a novel, clinically meaningful option for this subgroup, which can be identified through routine diagnostics.
Gianluca Pirozzi, senior vice president and head of development, regulatory and safety at Alexion, AstraZeneca Rare Disease, said CARES is the first Phase 3 program to show that targeting existing amyloid fibril deposits can deliver survival and cardiovascular benefits in adults with kappa AL amyloidosis. He said the findings underscore anselamimab’s potential as a first‑line therapy on top of standard of care and highlighted the company’s broader amyloidosis portfolio and plans to continue engagement with health authorities to advance the anti‑fibril approach. Results from CARES have been published in the Journal of Clinical Oncology and will be presented at the 2026 American Society of Clinical Oncology Annual Meeting.
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