The FDA approved Pfizer’s transthyretin stabilizer tafamidis, the first treatment for cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM), a rare, incurable disease. Pfizer will sell the oral drug in 2 dosage forms under the names Vyndaqel and Vyndamax. According to Reuters, Pfizer set the list price at $225,000 annually.
ATTR is characterized by the buildup of abnormal deposits of misfolded protein called amyloid in the heart and is defined by restrictive cardiomyopathy and progressive heart failure. The approval
was based on data from the pivotal phase 3 Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT), the first global, double-blind, randomized, placebo-controlled clinical drug study for this disease. In ATTR-ACT, tafamidis significantly reduced the hierarchical combination of all-cause mortality and frequency of cardiovascular-related hospitalizations compared with placebo over a 30-month period (P
= .0006). Additionally, individual components of the primary analysis demonstrated a relative reduction in the risk of all-cause mortality and frequency of cardiovascular-related hospitalization of 30% (P
= .026) and 32% (P
<.0001), respectively, with tafamidis versus placebo. Approximately 80% of total deaths were cardiovascular-related in both treatment groups.
Tafamidis also had significant and consistent treatment effects compared with placebo on functional capacity and health status first observed at 6 months and continuing through 30 months. Specifically, tafamidis reduced the decline in performance on the 6-minute walk test (P
<.0001) and reduced the decline in health status as measured by the Kansas City Cardiomyopathy Questionnaire–Overall Summary score (P
Previous options included symptom management, and, in rare cases, heart (or heart and liver) transplant. It is estimated that the prevalence of ATTR-CM is approximately 100,000 people in the United States and only 1% to 2% of those patients are diagnosed.
According to the Amyloidosis Foundation, wild-type ATTR is considered a disease of aging and typically affects men; patients are being diagnosed at a younger age. In some cases, the first symptom is carpal tunnel syndrome as proteins deposit in the wrist; protein involvement may also involve the spine or tendons in the arm. The foundation said that for hereditary ATTR, there are approximately 136 different genetic variations in ATTR, and at least 60 genetic variations in non-TTR hereditary amyloidosis diseases.
The recommended dosage is either Vyndaquel 80 mg orally once daily, taken as four 20-mg capsules, or Vyndamax 61 mg orally once daily, taken as a single capsule. Pfizer said that Vyndamax was developed for patient convenience and that the 2 formulations are not substitutable on a per-milligram basis.