Tafamidis Reduces All-Cause Mortality, Hospitalization Frequency in TTR-CM

Brenda Cooperstone, MD

Topline results from the phase 3 ATTR-ACT trial have been announced, revealing that tafamidis (Vyndaqel, Pfizer) led to a significant reduction in both all-cause mortality and the frequency of cardiovascular-related hospitalizations in patients with transthyretin cardiomyopathy (TTR-CM) in comparison with placebo.

These results are considered somewhat unexpected, as tafamidis was previously filed for approval with the US Food and Drug Administration (FDA) and rejected in 2012.

The multicenter, double-blind, international trial included 441 patients with TTR-CM, either acquired hereditarily or otherwise, and randomized them either tafamidis 20 mg or 80 mg, or placebo for 30 months. In addition to a significant reduction in the composite primary outcome, the drug was well tolerated, according to Pfizer. The news is welcome, as TTR-CM is a rare, progressive and universally fatal disease with no approved treatments. It is also believed to be vastly underdiagnosed.

“These topline results are important for people with transthyretin cardiomyopathy and bring us one step closer to realizing the potential for a new treatment for those in desperate need,” Brenda Cooperstone, MD, the senior vice president and chief development officer of rare disease at Pfizer Global Product Development, said in a statement. "We look forward to sharing the detailed results of the study with the cardiovascular community and discussing these data with health authorities to determine an appropriate regulatory path forward.”

Secondary outcomes of the trial will also report on 6-minute walk test and Kansas City Cardiomyopathy Questionnaire scores, cardiovascular-related mortality, TTR stabilization at month 1, the frequency of cardiovascular-related hospitalization, and all-cause mortality.

“Our findings offer real hope for people with transthyretin cardiomyopathy and their families,” Mat Maurer MD, the Arnold and Arlene Goldstein professor of Cardiology, Columbia University Vagelos College of Physicians and Surgeons, said. “As health care professionals, all we can do right now is manage symptoms of the disease, as there are no approved pharmacological treatment options at this time. The need for medicines that treat transthyretin cardiomyopathy is critical.”

Pfizer’s molecule received a Fast Track designation by the FDA in June 2017. Previously, it received Orphan Drug Designation in 2011.