AstraZeneca’s hopes for a breakthrough in AL amyloidosis treatment have hit a roadblock. In a key phase 3 trial, its investigational anti-fibril antibody, anselamimab, failed to achieve the primary endpoint—reducing all-cause mortality or cardiovascular hospitalizations in patients with late-stage light chain (AL) amyloidosis.
The global study enrolled 406 patients across 19 countries with stage IIIa or IIIb AL amyloidosis. While the trial results did not show a statistically significant reduction in deaths or hospitalizations, AstraZeneca noted a “highly clinically meaningful improvement” in a prespecified patient subset—though the company did not disclose details or supporting data.
Originally developed by Caelum Biosciences and acquired by AstraZeneca in 2021, anselamimab is a monoclonal antibody designed to deplete light chain amyloid fibrils. AstraZeneca positioned it as a potential blockbuster, touting its innovative mechanism aimed at clearing amyloid deposits to improve cardiac and renal function in affected patients.
Despite the missed primary endpoint, AstraZeneca emphasized that the treatment was generally well tolerated, with adverse events distributed evenly between treatment and placebo groups. The company plans to continue monitoring data to assess efficacy and safety in targeted subgroups.
AL amyloidosis, a progressive and often fatal rare disease, results from misfolded light chain proteins forming fibrils that accumulate in vital organs like the heart and kidneys. While survival rates have improved, many patients still die within months or years of diagnosis, often due to heart failure.
This setback adds to a growing list of challenges for AstraZeneca’s rare disease unit, Alexion, which has faced several recent clinical disappointments. Alexion CEO Marc Dunoyer reiterated the promise of anselamimab’s mechanism in today’s statement, noting its potential to treat advanced-stage patients with few alternatives.
The landscape for AL amyloidosis therapies remains competitive and uncertain. In May, rival biotech Prothena halted development of its own phase 3 candidate and announced deep organizational cuts. As the race to address this high-unmet-need disease continues, AstraZeneca will need to reassess its path forward with anselamimab.
