Antibody ALXN2220 (Formerly NI006) for the Treatment of Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis is an increasingly recognized infiltrative cardiomyopathy that is implicated in a growing number of cases of heart failure. Although it was once considered a disease without a cure, there have been rapid advances in pharmacotherapy over recent decades. The agents currently approved by the United States Food and Drug Administration-tafamidis and acoramidis-are transthyretin stabilizers that prevent the breakdown of the physiologic transthyretin tetramer into fibril-forming monomers. While these agents help prevent disease progression, they do not reverse existing disease. ALXN2220 (previously called NI006) addresses this unmet need. A recombinant human IgG1 monoclonal antibody with high specificity for transthyretin monomers and amyloid fibrils, ALXN2220 stimulates macrophage-mediated phagocytosis of deposited amyloid fibrils. Phase 1 studies have demonstrated the tolerability of doses ranging from 0.3 to 60 mg/kg/month. At doses higher than 10 mg/kg/month, ALXN2220 has demonstrated the ability to decrease cardiac tracer uptake on scintigraphy and decrease the extracellular volume on cardiac magnetic resonance imaging at 4 and 12 months when compared with placebo. These imaging parameters are known surrogates for the burden of cardiac amyloid deposition. In addition, significant reductions in levels of n-terminal proBNP and troponin T, as well as improvements in Kansas City Cardiomyopathy Questionnaire scores were also noted. The adverse effect and immunogenicity profiles were encouraging as well. A multinational, placebo-controlled phase 3 trial (DepleTTR-CM) is ongoing to assess long-term efficacy, functional outcomes, and survival impact. These results are expected to provide critical real-world evidence on ALXN2220's role in transthyretin cardiac amyloidosis management.