Tafamidis is an effective and safe therapy for treating patients with transthyretin amyloid cardiomyopathy (ATTR-CM), based on findings from the ATTR-ACT trial presented Aug. 27 at ESC Congress 2018 and published in the New England Journal of Medicine.

ATTR-CM – a rare, progressive and fatal disease that is either hereditary (mutations in the TTR gene) or acquired – typically presents in patients between 50 years and 80 years. There are currently no approved drugs to improve survival, which on average is three to five years after diagnosis. However, tafamidis has received orphan drug designation from the European Medicines Agency (EMA) and Fast Track designation from the U.S. Food and Drug Administration (FDA).

In ATTR-ACT, researchers randomized 441 patients from 48 centres in 13 countries to receive tafamidis (80 mg), tafamidis (20 mg) or placebo once a day, for 30 months. The primary endpoint was the composite of all-cause death and cardiovascular-related hospitalizations from baseline to 30 months. The two tafamidis groups were combined (N=264) and compared with the placebo group (N=177). Secondary outcomes included the change from baseline to 30 months in exercise capacity (assessed with the six-minute walk test) and in health-related quality of life.

Overall results found tafamidis significantly reduced death and cardiovascular-related hospitalization compared to placebo (p=0.0006). During the 30-month follow-up, 78 (29.5 percent) patients receiving tafamidis died compared with 76 (42.9 percent) receiving placebo. Rates of cardiovascular-related hospitalizations were 52.3 percent in the tafamidis group compared with 60.5 percent in the placebo group. Researchers also noted patients in the tafamidis group had better exercise capacity and quality of life than those taking placebo. Additionally, discontinuation of tafamidis due to treatment-related adverse events was less common in the treatment group compared with placebo.

"There are no medications specifically approved for the treatment of transthyretin amyloid cardiomyopathy," said Professor Claudio Rapezzi, principal investigator, University of Bologna, Italy. "Tafamidis improved survival and quality of life, and reduced hospitalizations, indicating that it could be an effective therapy for these patients. A submission to the regulatory authorities for marketing approval is in process as a consequence of this study."

In a related editorial, C. Cristina Quarta, MD, and Scott D. Solomon, MD, FACC, write that the ATTR-ACT findings "offer hope for patients" and "suggest new ways forward in testing therapies for new diseases." However, they also caution that the findings raise further questions "about the mechanism of action of tafamidis, the time course of benefit, and the timing of treatment in the course of a patient's disease" and suggest additional studies "to determine whether there are important therapeutic differences between transthyretin stabilization and transthyretin knockdown."

Keywords: ESC18, ESC Congress, Prealbumin, Benzoxazoles, Amyloid, Amyloidosis, Cardiomyopathies

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