Rare Daily Staff

The U.S. Food and Drug Administration granted Priority Review to Pfizer for its application to market tafamidis, its treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), a rare, fatal, and underdiagnosed condition associated with progressive heart failure.

ATTR-CM is caused by destabilization of a transport protein called transthyretin, which is composed of four identical subunits known as tetramers. In ATTR-CM, heart failure occurs when unstable tetramers dissociate, resulting in misfolded proteins that aggregate into amyloid fibrils and deposit predominantly in the heart.

Tafamidis is a small molecule that selectively binds at specific sites on the transthyretin tetramer to prevent destabilization of the transthyretin transport protein and formation of amyloid that causes ATTR-CM.

The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The agency is expected to act on the Pfizer application by July 2019.

Pfizer has submitted two applications based on two forms of tafamidis: meglumine salt and free acid. The agency granted Priority Review to the application for tafamidis meglumine. The free acid formulation is undergoing standard review.

“The diagnosis of ATTR-CM is often delayed, primarily because disease awareness is low, and patients often present with symptoms similar to more common causes of heart failure. In fact, we believe less than one percent of patients living with this disease are currently diagnosed,” said Brenda Cooperstone, Senior Vice President and Chief Development Officer, Rare Disease, Pfizer Global Product Development. “The FDA’s filing acceptance is an encouraging step toward our goal of further raising awareness and providing a treatment option for ATTR-CM patients who are in desperate need of an approved pharmacologic therapy.”

The submission is based on findings from the pivotal phase 3 study that evaluated the efficacy, safety, and tolerability of tafamidis meglumine compared to placebo for the treatment of patients with ATTR-CM.

In the primary analysis of the study, tafamidis met the primary endpoint, demonstrating a significant reduction in the hierarchical combination of all-cause mortality and frequency of cardiovascular-related hospitalizations compared to placebo over a 30-month period in patients with wild-type or hereditary ATTR-CM.

Tafamidis was well tolerated, with an observed safety profile comparable to placebo.

Tafamidis was granted Orphan Drug designation for ATTR-CM in the United States, European Union, and Japan. The FDA also granted tafamidis Fast Track and Breakthrough Therapy designations for ATTR-CM.

 

January 15, 2019
Photo: Brenda Cooperstone, Senior Vice President and Chief Development Officer, Rare Disease, Pfizer Global Product Development

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