AstraZeneca’s investigational anti-fibril therapy, anselamimab, did not meet its primary endpoint in a Phase III trial in the overall light chain amyloidosis population, but showed benefit in kappa patients.
In the global CARES programme, which enrolled patients with Mayo stages IIIa (NCT04512235) and Mayo stages IIIb (NCT04504825), the potential first-in-class 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 (SoC) plasma cell dyscrasia (PCD) treatments, compared to placebo.
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In a prespecified subgroup analysis of 72 patients with kappa predominant light chain isotype, anselamimab improved survival by 62%, measured by all-cause mortality (ACM) and reduced the frequency of cardiovascular hospitalisations (CVH) by 71%, compared to placebo.
The reduction in the risk of ACM in the kappa subgroup was observed in both trials comprising the CARES Phase III clinical programme among patients with kappa isotype with Mayo stage IIIa disease (75%) and Mayo stage IIIb disease (48%).
At 50 weeks, numerical improvements favoured anselamimab in key secondary endpoints, including quality and functional capacity, again in patients with kappa AL amyloidosis.
In July, AstraZeneca reported that the overall population of patients with AL amyloidosis, however, did not see benefit from treatment with anselamimab. In the 328 patients with the lambda isotype in the study, the mortality rate was 33.3% in those treated with anselamimab and 33.9% for those who received 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.
The kappa data was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago, Illinois, from 29 May to 1 June.
AstraZeneca acquired Alexion, the original owner of the drug, in a deal worth up to £39bn in 2020, which included anselamimab among other rare disease drugs. The company is now operated as a subsidiary of AstraZeneca.
This is a second hit to the monoclonal antibody (mAb) approach in AL amyloidosis after Prothena’s mAb, birtamimab, failed to meet the primary endpoint in a Phase III trial, with the company announcing it was discontinuing development of the drug in May 2025.
The only drug approved by the US Food and Drug Administration (FDA) for AL amyloidosis is Darzalex Faspro (daratumumab and hyaluronidase-fihj) in combination with cyclophosphamide, bortezomib, and dexamethasone.
There are some therapies in the pipeline, including Immix Biopharma’s NXC-201, which showed promise in relapsed/refractory AL amyloidosis in a Phase Ib/IIa study. The therapy has also received orphan drug designation by the agency.
