In a setback to one of its rarer disease pipelines, AstraZeneca’s amyloidosis antibody, anselamimab, failed to significantly reduce all-cause mortality and CV hospitalizations in the CARES Phase 3 trial’s overall patient population.
- AL amyloidosis is a rare disease (only about 70k people worldwide) where misfolded light chain proteins form toxic amyloid deposits in the heart and kidneys.
- These deposits cause progressive organ damage and dysfunction, often leading to death from cardiac failure.
- Current treatments focus on plasma cell dyscrasia but don’t address existing amyloid deposits that damage organs.
The CARES clinical program was the largest prospective cardiac AL amyloidosis investigation to date, enrolling 406 patients to test whether anselamimab could reduce all-cause mortality and cardiovascular hospitalizations when added to standard background therapy.
- All patients had Mayo disease stages IIIa (281 patients) and IIIb (125 patients), which are considered the most advanced.
- Treatment with anselamimab was administered weekly for 4 weeks, then every 2 weeks for 18 months but led to no significant improvements in mortality or hospitalization rates.
However, despite the overall trial not reaching statistical significance, researchers identified meaningful clinical benefits in a “prespecified patient subgroup” that experienced extended survival and fewer cardiovascular hospitalizations compared to placebo.
- The subgroup analysis was planned before the trial began, lending credibility to the findings.
- That said, AstraZeneca has not released any description or data regarding this patient subgroup.
So what do these mixed results mean for AstraZeneca?
- While anselamimab didn’t achieve broad efficacy across all patients, the meaningful benefits seen in a defined subgroup suggest it could still fill a critical treatment gap.
- AstraZeneca didn’t reveal its plans for anselamimab, but will still share this data with global health authorities and present it at a coming medical meeting.
The Takeaway
It’s never easy when a drug fails to meet expectations in later stage trials and while we don’t have the full data yet, AstraZeneca’s update makes it seem like anselamimab’s scope could be even more limited than intended. Hopefully we’ll learn more about the patient subgroup that significantly benefitted from the drug in case AZ pivots its efforts to them.
