Abstract

Amyloid light chain (AL) amyloidosis is a rare, typically fatal disease characterized by accumulation of misfolded immunoglobulin light chains (LCs). Birtamimab is an investigational humanized monoclonal antibody designed to neutralize toxic LC aggregates and deplete insoluble organ-deposited amyloid via macrophage-induced phagocytosis. VITAL was a phase 3 randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of birtamimab + standard of care (SOC) in 260 newly diagnosed, treatment-naive patients with AL amyloidosis. Patients received 24 mg/kg intravenous birtamimab + SOC or placebo + SOC every 28 days. The primary composite endpoint was time to all-cause mortality (ACM) or centrally adjudicated cardiac hospitalization =91 days after first study drug infusion. The trial was terminated early after an interim futility analysis; there was no significant difference in the primary composite endpoint (hazard ratio [HR] = 0.826; 95% confidence interval [CI] 0.574-1.189; log-rank P = .303). A post hoc analysis in Mayo Stage IV patients, those at highest risk of early mortality, showed significant improvement in time to ACM with birtamimab at month 9 (HR = 0.413; 95% CI: 0.191-0.895; log-rank P = .021). At month 9, 74% of Mayo Stage IV patients treated with birtamimab and 49% of those given placebo survived. Overall, the rates of treatment-emergent adverse events (TEAEs) and serious TEAEs were generally similar between treatment arms. A confirmatory phase 3 randomized, double-blind, placebo-controlled clinical trial of birtamimab in patients with Mayo Stage IV AL amyloidosis (AFFIRM-AL; NCT04973137) is currently enrolling. The VITAL trial was registered at www.clinicaltrials.gov as #NCT02312206.

View details for DOI 10.1182/blood.2022019406

View details for PubMedID 37366170