The mechanism of action, pharmacological characteristics, and clinical utility of the amyloid depleter birtamimab for the potential treatment of AL amyloidosis.

Amyloid light chain (AL) amyloidosis is a progressive plasma cell disorder caused by amyloid deposition resulting in organ damage and failure. Current standard-of-care treatments target clonal plasma cells, the source of misfolded light chains (amyloid precursors), yet only half of patients with advanced disease survive ≥6 months. The amyloid depleter birtamimab is an investigational humanized monoclonal antibody that binds misfolded and light chains with high specificity and was designed to neutralize soluble toxic light chain aggregates and promote phagocytic clearance of deposited amyloid. Post hoc analyses from the Phase 3 VITAL trial suggested birtamimab plus standard of care confers a survival benefit in patients with advanced (Mayo Stage IV) AL amyloidosis. AFFIRM-AL (NCT04973137), a Phase 3 confirmatory trial of birtamimab plus standard of care in patients with Mayo Stage IV AL amyloidosis, is ongoing. This review summarizes birtamimab's mechanism of action, attributes, and potential clinical utility.