Key Information
Amyloid light chain (AL) amyloidosis - a progressive disorder caused by misfolded light chains produced by plasma cells - is associated with high mortality, poor quality of life, and increased healthcare costs, particularly in newly diagnosed patients with advanced disease (Mayo 2012 Stage IV, median overall survival 6 months). Birtamimab is a monoclonal antibody designed to neutralize circulating soluble and deplete deposited insoluble amyloid by promoting phagocytic clearance.
In 2018, the Phase 3 VITAL study - a multicenter, global, randomized, double-blind, placebo-controlled study (NCT02312206) conducted in newly diagnosed, treatment-naive patients with AL amyloidosis and cardiac involvement - was terminated based on a futility analysis of the primary endpoint (time to all-cause mortality [ACM] or time to cardiac hospitalization >=91 days after first study drug infusion); the final hazard ratio (HR) numerically favored birtamimab + standard of care (SOC) over placebo + SOC (0.826 [95% CI: 0.574, 1.189]). Post hoc analysis of ACM over 9 months revealed a significant survival benefit (HR=0.413 [95% CI: 0.191, 0.895]) in patients at high risk for early death (i.e., Mayo 2012 Stage IV). Here we report the results of sensitivity analyses of ACM in the subgroup of patients with Mayo 2012 Stage IV AL amyloidosis, adjusting for key baseline variables.