First Treatments for Transthyretin Amyloid Cardiomyopathy Get FDA Approval

The FDA has approved Vyndaqel and Vyndamax for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis.

The Food and Drug Administration (FDA) has approved Vyndaqel (tafamidis meglumine; Pfizer) and Vyndamax (tafamidis; Pfizer) for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. These 2 oral medications are the first therapies FDA-approved for this indication.

Vyndaqel and Vyndamax both contain tafamidis, a selective stabilizer of transthyretin (TTR). Tafamidis binds to TTR at the thyroxine binding sites, stabilizing the tetramer of the transthyretin transport protein and slowing the formation of amyloid that causes ATTR-CM.

The approval was based on data from a phase 3 double-blind, placebo-controlled study (Transthyretin Amyloidosis Cardiomyopathy Clinical Trial [ATTR-ACT]) in 441 patients with wild type or hereditary ATTR-CM. Patients were randomized in a 1:2:2 ratio to receive Vyndaqel 20mg, Vyndaqel 80mg, or matching placebo once daily for 30 months, in addition to standard of care (e.g., diuretics). The primary endpoint of the study was the hierarchical combination of all-cause mortality and frequency of cardiovascular-related hospitalizations, which was defined as the number of times a patient was hospitalized for cardiovascular-related morbidity.

Results showed a significant reduction (P =.0006) in all-cause mortality and frequency of cardiovascular-related hospitalizations in the pooled Vyndaqel 20mg and 80mg groups vs placebo. An analysis of individual components showed a 30% relative reduction in the risk of death when compared with placebo (hazard ratio [HR] 0.70, 95% CI: 0.51, 0.96; P =.026). Moreover, there were significantly fewer cardiovascular-related hospitalizations with Vyndaqel compared with placebo with a reduction in risk of 32% corresponding to a relative risk ratio of 0.68.

In addition, a significant treatment effect was observed with Vyndaqel at 6 months and remained consistent through 30 months on both the 6-Minute Walk Test (6MWT) and the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score, used to assess functional capacity and health status, respectively. The frequency of adverse events in patients treated with Vyndaqel was found to be similar to that of placebo.

Vyndaqel is supplied in 20mg capsules while Vyndamax is available in 61mg capsules. The capsules are not substitutable on a per mg basis and their recommended doses are different; Vyndamax was developed for patient convenience, allowing for administration of a single capsule.

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This article originally appeared on MPR