New therapies to treat cardiac amyloidosis

Review advancements in therapies for transthyretin (ATTR-CM) and immunoglobulin light chain (AL-CM) cardiac amyloidosis.

In ATTR-CM, tafamidis remains the cornerstone therapy, with Food and Drug Administration (FDA) approval for over 5 years. Acoramidis, another transthyretin stabilizer, has very recently been FDA-approved following positive results in the ATTRibute-CM trial. Vutrisiran, a transthyretin gene silencer, demonstrated efficacy in the HELIOS-B trial and awaits FDA review. Eplontersen's CARDIO-TTRansform trial, the largest ATTR-CM study to date, is expected to report by late 2025. Innovative approaches such as NTLA-2001 (a CRISPR-Cas9 therapy) and fibril depleters like ALXN2220 and coramitug are advancing in clinical trials. In AL-CM, daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) has established itself as the standard of care. Novel antiplasma cell therapies include CAR-T cells and bispecific antibodies (teclistimab) and fibril depleters. Birtamimab improved survival in advanced AL-CM during the VITAL trial and is under investigation in AFFIRM-AL. Anselamimab is in phase III CARES trials, whereas AT-02 undergoes early-phase testing for ATTR-CM and AL-CM.

The therapeutic landscape for ATTR-CM and AL-CM is rapidly evolving, driven by novel therapies targeting diverse mechanisms. Ongoing clinical trials promise to further refine the standard of care and improve outcomes for patients with cardiac amyloidosis.