AstraZeneca has reported that its global Phase III CARES programme for anselamimab, an investigational anti-fibril therapy for AL amyloidosis, failed to meet its primary endpoint in the overall patient population.

 

This, while delivering what the company called “highly clinically meaningful” benefits in a prespecified subgroup of patients with kappa light chain disease.

 

The programme evaluated anselamimab as a first-line add-on to standard plasma cell dyscrasia therapy in patients with advanced cardiac AL amyloidosis.

 

In the overall population, the study did not achieve statistical significance for its primary hierarchical endpoint combining all-cause mortality (ACM) and cardiovascular hospitalisations (CVH).

 

However, results in the prespecified kappa light chain subgroup stood in stark contrast. Patients receiving anselamimab showed a 62% improvement in survival, with a hazard ratio of 0.38, alongside a 71% reduction in cardiovascular hospitalisations compared with placebo.

 

The company also reported that survival benefits in the kappa subgroup were consistent across both Phase III trials, including patients with Mayo stage IIIa and IIIb disease. No benefit was observed in patients with lambda light chain disease.

 

Secondary endpoints at 50 weeks showed numerical improvements in quality of life and functional capacity for kappa patients, including gains on the Kansas City Cardiomyopathy Questionnaire and the Six-Minute Walk Test, though neither reached statistical significance.

 

Ashutosh Wechalekar, lead principal investigator, said: “People living with advanced AL amyloidosis often face persistent, progressive and debilitating organ damage with no available options to target and clear existing amyloid fibril deposits. 

 

"Results from the CARES Phase III programme show that anselamimab, a monoclonal antibody with a novel mechanism of action designed to target and remove amyloid fibrils, improved survival and reduced the frequency of cardiovascular hospitalisations in patients with kappa light chain amyloidosis. 

 

"Anselamimab has the potential to offer a novel, clinically meaningful therapeutic for this subgroup of patients with kappa AL amyloidosis who can be easily identified by simple, routinely-used diagnostics.”

 

Gianluca Pirozzi, Senior Vice President at Alexion, AstraZeneca Rare Disease, said: “The CARES Phase III programme is the first to show that targeting existing deposits of amyloid fibrils could deliver clinically meaningful survival and cardiovascular benefit in adults with kappa light chain amyloidosis, underscoring anselamimab's potential as a first-line therapy on top of standard of care. 

 

"With anselamimab and our leading amyloidosis portfolio, we are advancing pioneering science with the goal of addressing critical treatment gaps. We look forward to continued engagement with health authorities to advance this potential first-in-class anti-fibril therapy.”

 

AL amyloidosis is a rare, progressive condition caused by misfolded light chain proteins that accumulate as amyloid fibrils in organs—most often the heart and kidneys—leading to organ failure.