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

AstraZeneca's experimental rare disease drug anselamimab has failed to meet its primary endpoint in two Phase III trials for light chain amyloidosis, the pharmaceutical giant announced on Wednesday. Despite this setback, the company reported a "clinically meaningful improvement" in a prespecified patient subgroup, leaving room for potential future development.

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 disorder characterized by the accumulation of abnormal protein deposits in organs, particularly the heart and kidneys. The primary endpoint, which combined all-cause mortality and frequency of cardiovascular hospitalizations, was not met across the overall patient population.

However, AstraZeneca highlighted a significant finding within a specific patient subgroup, though details of this subgroup were not disclosed. Dr. Ashutosh Wechalekar, lead principal investigator and professor at University College London, stated, "The potential to extend survival and reduce cardiovascular hospitalizations would represent a practice-changing advancement for this patient group."

The company reported that anselamimab was well-tolerated, with most adverse events balanced between the treatment and placebo arms. A full data analysis is underway, with results expected to be presented at an upcoming medical meeting.

Anselamimab's Background and Market Context

Anselamimab, an antibody targeting amyloid deposits, was acquired by AstraZeneca through its 2021 purchase of Caelum Biosciences for approximately $150 million, with potential additional payments of up to $350 million based on regulatory and commercial milestones. The drug has received fast track and orphan drug designations from the FDA, as well as orphan drug status in the European Union and Japan.

This setback for anselamimab follows a trend of challenges in the amyloidosis treatment landscape. Earlier this year, Prothena discontinued development of its experimental treatment birtamimab after a Phase III trial failure. Takeda and GSK similarly halted work on their respective candidates in 2019.

Currently, Johnson & Johnson's Darzalex, approved by the FDA in 2021 under an accelerated pathway, is available for newly diagnosed AL amyloidosis patients when used in combination with other medicines. Traditional treatments also include chemotherapy and stem cell transplants.

AstraZeneca's Rare Disease Portfolio and Recent Developments

The anselamimab trial results come at a crucial time for AstraZeneca's rare disease division, Alexion, which has been expanding since the company's acquisition of Alexion Pharmaceuticals in 2020. Despite this setback, AstraZeneca has seen recent successes in other areas of its portfolio.

Earlier this week, the company reported positive results for baxdrostat, a treatment for uncontrolled or treatment-resistant hypertension, in a Phase III trial. Baxdrostat was acquired through AstraZeneca's 2023 purchase of CinCor Pharma. Additionally, in early July, Alexion gained access to new AAV vectors from Japanese biotech JCR Pharmaceuticals to support its gene therapy program.

As AstraZeneca continues to analyze the anselamimab data and explore its potential in specific patient subgroups, the company remains committed to advancing its rare disease pipeline through both internal development and strategic acquisitions.