The Evolving Treatment Landscape of ATTR-CM

Summary for Physicians: Current Treatment Landscape and Key Trials in ATTR-CM

Current treatment landscape of ATTR-CM: Transthyretin amyloid cardiomyopathy (ATTR-CM) treatment options are primarily divided into 2 categories:

1. Transthyretin stabilizers: These drugs aim to prevent the misfolding of TTR proteins, thus reducing amyloid deposition. Key agents include:
   1. Tafamidi
   2. Acoramidis
   3. Diflunisal
2. Transthyretin silencers: These therapies work by reducing the production of abnormal TTR proteins. Notable drugs in this class include:
   1. Patisiran
   2. Vutrisiran
   3. Inotersen
   4. Eplontersen

Phase 3 Trial: ATTRibute-CM (acoramidis): The ATTRibute-CM trial investigates the use of acoramidis in patients with ATTR-CM. The top-line results, as discussed by Dr Judge, encompass the following key aspects:

• Design: A phase 3, randomized, placebo-controlled trial focusing on the efficacy of acoramidis in improving cardiac function and outcomes in patients with ATTR-CM.
• End points: Primary end points typically include measures of cardiac function (eg, NT-proBNP, 6-minute walk test), and secondary end points often involve safety, quality of life, and mortality.
• Efficacy and safety: The trial results suggest that acoramidis significantly improves key clinical end points compared with placebo, demonstrating both efficacy in reducing symptoms and a favorable safety profile.

Tafamidis and the ATTR-ACT trial: The ATTR-ACT trial evaluated tafamidis, a transthyretin stabilizer, and has previously reported positive results. Key findings from this trial include:

• Efficacy: Tafamidis significantly improved survival and reduced cardiovascular-related hospitalizations in patients with ATTR-CM.
• Safety: The drug was well tolerated with manageable adverse effects, supporting its use as a frontline treatment in ATTR-CM.

These studies highlight the ongoing advancements in the treatment of ATTR-CM, with both stabilizers and silencers offering meaningful therapeutic options for patients.