Monitoring Tafamidis, the Most Expensive Cardiac Medication: Are Serum Transthyretin Levels the Answer?

Once considered a rare condition, transthyretin (TTR) cardiac amyloidosis (ATTR-CM) is now increasingly diagnosed as a result of heightened awareness and improved diagnostics. The TTR stabilizer tafamidis is the only medication currently approved by the Food and Drug Administration (FDA) for ATTR-CM. The pivotal ATTR-ACT (Tafamidis in Transthyretin Amyloidosis Cardiomyopathy Clinical Trial) demonstrated that tafamidis treatment slowed progression of disease and was associated with reduced mortality and cardiovascular hospitalization. Another TTR stabilizer, AG10 (acoramidis), is being studied in a phase 3 clinical trial of ATTR-CM, as are several RNA-silencer therapies.

Tafamidis is a small molecule that binds to the thyroxine-binding site of the TTR tetramer, thereby slowing the process of dissociation into amyloidogenic monomer. In the ATTR-ACT study, tafamidis was found to be well tolerated, with a similar incidence of adverse events between those receiving tafamidis and placebo. No drug-specific safety monitoring was recommended by the FDA. However, with a list price of $225,000 per year, tafamidis treatment results in a significant financial burden for many patients, even with insurance coverage. Therefore, with an expensive treatment that has relatively few side effects in this slowly progressive disease, patients and providers commonly wonder whether tafamidis is working and naturally seek measures of efficacy.