AstraZeneca's Amyloidosis Drug Fails Primary Endpoint in Late-Stage Trials, Shows Promise in Subgroup

AstraZeneca's experimental rare disease drug, anselamimab, has failed to meet its primary endpoint in two late-stage clinical trials for light chain amyloidosis. However, the pharmaceutical giant reports a potential benefit in a specific patient subgroup, keeping hopes alive for the treatment's future.

Trial Results and Implications

The global Phase III trials, collectively known as Cardiac Amyloid Reaching for Extended Survival (CARES), enrolled 406 patients with light chain amyloidosis, a rare condition where abnormal antibody proteins accumulate in and damage organs, particularly the heart and kidneys. The primary endpoint, a combination of time to all-cause mortality and frequency of cardiovascular hospitalizations, was not met across the overall patient population.

Despite this setback, AstraZeneca reported a "clinically meaningful improvement" in a prespecified patient subgroup, though details of this subgroup were not disclosed. The company plans to conduct a fuller data analysis and present the results at an upcoming medical meeting.

Dr. Ashutosh Wechalekar, a professor at University College London and lead principal investigator of the trials, stated, "The potential to extend survival and reduce cardiovascular hospitalizations would represent a practice-changing advancement for this patient group."

Anselamimab's Background and Development

Anselamimab, an antibody designed to target and eliminate amyloid deposits, was acquired by AstraZeneca through its 2021 purchase of Caelum Biosciences. The deal, valued at approximately $150 million plus potential milestone payments of up to $350 million, was part of AstraZeneca's strategy to expand its rare disease portfolio following the acquisition of Alexion Pharmaceuticals in 2020.

The drug has been granted fast track and orphan drug designation by the FDA for treating amyloidosis, as well as orphan drug status in the European Union and Japan. An estimated 74,000 people worldwide suffer from AL amyloidosis, underscoring the need for effective treatments in this area.

Competitive Landscape and Industry Challenges

AstraZeneca's setback with anselamimab highlights the challenges faced by pharmaceutical companies in developing treatments for rare diseases, particularly amyloidosis. Several other drug developers have encountered difficulties in this space:

• Prothena discontinued development of its experimental treatment birtamimab in May after it failed to extend patient survival in a Phase 3 trial.
• Takeda and GSK halted work on their respective amyloidosis prospects in 2019.

Currently, Johnson & Johnson's Darzalex, approved by the FDA in 2021 for use in combination with other medicines, is available for treating newly diagnosed AL amyloidosis patients. Chemotherapy and stem cell transplants are also used as treatment options.