Dr Bianchi on the Mechanism of Anselamimab in AL Amyloidosis

“Anselamimab is a monoclonal antibody that was designed with the intent of aiding the removal of amyloid fibrils from organs, which is a critical need in patients with systemic amyloidosis.”

Giada Bianchi, MD, associate director of the Amyloidosis Program at Brigham and Women’s Hospital and Dana-Farber Cancer Institute, as well as an assistant professor at Harvard Medical School, discussed the development, mechanism of action, and clinical evaluation of anselamimab (CAEL-101), which is being investigated in the treatment of patients with light chain (AL) amyloidosis.

Anselamimab is designed to promote the removal of amyloid fibrils from affected organs, Bianchi explained. The antibody was developed to address a critical unmet need in the disease: directly clearing amyloid deposits that accumulate in organs and contribute to progressive dysfunction, she said.

During preclinical evaluation, anselamimab demonstrated the ability to activate macrophages in vitro, Bianchi said. She described macrophages as “vacuum cleaner” cells that travel through the body, recognize amyloid material, and facilitate its removal. Additionally, in murine models containing amyloidomas, treatment with the antibody led to substantial reductions in amyloidoma size. Activity was observed in models involving both kappa and lambda light chains, although the kappa light chain amyloidomas appeared to respond more strongly to the agent, she explained.

These findings supported the advancement of anselamimab into early-phase clinical studies. According to Bianchi, early clinical evaluation did not reveal emerging adverse effects, suggesting that the antibody had a favorable safety profile. Signals of clinical activity observed during phase 2 testing subsequently prompted the development of the larger phase 3 CARES program, comprising the CAEL 101-301 (NCT04504825) and CAEL 101-302 (NCT04512235) trials.

The CARES trials were designed as randomized, double-blind, placebo-controlled studies evaluating anselamimab in patients with newly diagnosed AL amyloidosis and the most advanced forms of cardiac involvement, specifically Mayo stages IIIa and IIIb. Findings presented at the 2026 Society of Hematologic Oncology (SOHO) Annual Meeting showed that the CARES trials did not meet their primary end point of all-cause mortality (ACM) and cardiovascular-related hospitalization (CVH) rates vs placebo in the overall population, but statistically significant reductions in both ACM and CVH were observed among patients in the kappa isotype subgroup.