AstraZeneca’s plans to get an amyloidosis drug to market look further out of reach after the pharma’s anti-fibril antibody failed to reduce deaths and hospitalizations in a key phase 3 study.
The Big Pharma evaluated the light chain depleter antibody, called anselamimab, in a late-stage program spanning 406 patients across 19 countries with either stage IIIa or stage IIIb light chain (AL) amyloidosis. The study failed to tie anselamimab to a statistically significant reduction in all-cause mortality or frequency of cardiovascular hospitalizations, missing the primary endpoint, AstraZeneca announced in a July 16 release.
The U.K.-based Big Pharma claimed that the monoclonal antibody had demonstrated a “highly clinically meaningful improvement” in these endpoints in “a prespecified subgroup of patients,” but didn’t offer more data or identify this subgroup.
The therapy was well tolerated, with the majority of adverse events balanced between the anselamimab and placebo cohorts, AstraZeneca added.
This morning’s results are a blow to the anselamimab program, which as recently as last year (PDF) AstraZeneca had been touting to investors as a potential rare disease blockbuster that could be a growth driver for the company. AstraZeneca secured anselamimab when it bought out Caelum Biosciences back in 2021, at which point the therapy had already entered the phase 3 study.
AL amyloidosis is caused by defective plasma cells in the bone marrow that lead to the accumulation of amyloid fibrils in tissues and organs such as the kidneys and heart. Overall survival of AL amyloidosis patients has improved in recent decades, but many patients still die in the months and years after diagnosis, often from cardiac failure.
AstraZeneca had been betting that anselamimab’s novel depleter mechanism would allow it to eliminate deposited fibrils in order to improve overall survival, cardiac function and renal function.
The phase 3 fail also marks the latest setback for AstraZeneca’s rare disease unit Alexion, which has seen a number of programs derailed due to clinical efficacy in recent years.
“Alexion is pioneering a novel mechanism of action to address organ damage from existing amyloid deposits in patients with AL amyloidosis, a devastating disease often diagnosed in advanced stages with poor prognosis,” Alexion CEO Marc Dunoyer said in this morning’s release.
“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,” Dunoyer added.
For now, AstraZeneca will evaluate the phase 3 results “to further characterise the efficacy and safety of anselamimab,” the company said.
“While the study did not meet the primary endpoint in the overall patient population, results from a pre-defined subgroup suggest that anselamimab, by targeting and clearing amyloid deposits, may address a leading cause of organ damage and functional impairment in these patients,” Ashutosh Wechalekar, professor of medicine at University College London and the phase 3 program’s principal investigator, said in the release.
In May, Prothena saw a phase 3 trial of its own AL amyloidosis candidate end in failure, prompting the biotech to halt development and plan a “substantial reduction in organizational size.