AstraZeneca's AL Amyloidosis Drug Fails to Meet Primary Endpoint in Phase 3 Trial

AstraZeneca's hopes for a potential blockbuster drug in the rare disease space have been dealt a significant blow as its light chain (AL) amyloidosis candidate, anselamimab, failed to meet its primary endpoint in a pivotal phase 3 trial. The study, which involved 406 patients across 19 countries, did not demonstrate a statistically significant reduction in all-cause mortality or frequency of cardiovascular hospitalizations.

Trial Results and Implications

The late-stage trial evaluated anselamimab, an anti-fibril antibody, in patients with either stage IIIa or stage IIIb AL amyloidosis. Despite the setback, AstraZeneca reported that the drug showed a "highly clinically meaningful improvement" in a prespecified subgroup of patients, though specific details were not provided.

Marc Dunoyer, CEO of Alexion, AstraZeneca's rare disease unit, emphasized the novel mechanism of action of anselamimab, stating, "Anselamimab is the first and only investigational fibril depleter to show clinical benefit in AL amyloidosis, and these results underscore its potential to address a critical treatment gap in a prespecified subgroup of patients."

The company noted that the therapy was well-tolerated, with adverse events generally balanced between the anselamimab and placebo groups. AstraZeneca plans to further evaluate the phase 3 results to better characterize the efficacy and safety profile of the drug.

Industry Context and Future Outlook

This setback comes at a challenging time for AstraZeneca's rare disease portfolio. The company had previously touted anselamimab as a potential rare disease blockbuster and growth driver. AstraZeneca acquired the drug through its purchase of Caelum Biosciences in 2021, at which point the phase 3 trial was already underway.

The failure of anselamimab follows a similar outcome for Prothena's AL amyloidosis candidate in May, highlighting the difficulties in developing effective treatments for this devastating disease. AL amyloidosis, caused by defective plasma cells in the bone marrow, leads to the accumulation of amyloid fibrils in various organs, particularly the heart and kidneys.

Despite improvements in overall survival rates for AL amyloidosis patients in recent decades, many still succumb to the disease, often due to cardiac failure. The unmet need in this area underscores the importance of continued research and development efforts in the field.