Alexion Light Chain Amyloidosis Therapy Misses Endpoint in Phase 3 Study

Rare Daily Staff

Alexion, AstraZeneca Rare Disease, reported that a phase 3 study of its experimental therapy anselamimab in light chain amyloidosis failed to achieve statistical significance in its primary endpoint in the overall patient population.

The primary endpoint was defined as a hierarchical combination of time to all-cause mortality and frequency of cardiovascular hospitalizations. All patients in the clinical program received background standard of care for plasma cell dyscrasia.

Light chain (AL) amyloidosis is a systemic and progressive type of amyloidosis in which immunoglobulin light chain proteins are produced abnormally by defective plasma cells in the bone marrow. These abnormal proteins misfold, aggregate, and form amyloid fibrils that deposit and accumulate in tissues or organs, particularly in the heart and kidneys. The deposition can cause progressive damage and may lead to premature death, most commonly due to cardiac failure.

Anselamimab is an investigational, potentially first-in-class anti-fibril monoclonal antibody designed to improve organ function by reducing or eliminating amyloid deposits in the tissues and organs of patients living with AL amyloidosis. By binding with specificity to targets within amino acids on misfolded amyloid fibrils, anselamimab promotes destruction and clearance of amyloid deposits, while sparing native free light chains from destruction.

The U.S. Food and Drug Administration granted anselamimab Fast Track and Orphan Drug designations. The European Commission and the Ministry of Health, Labour and Welfare of Japan also gave it Orphan Drug designation for the treatment of AL amyloidosis.

“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,” said Ashutosh Wechalekar, professor of medicine and hematology at University College London and lead principal investigator of the program. “The potential to extend survival and reduce cardiovascular hospitalizations would represent a practice-changing advancement for this patient group.”