The U.S. Food and Drug Administration approved Pfizer’s oral drug tafamidis to treat the rare heart disease transthyretin-mediated amyloidosis in adults. It is the first drug approved in the United States to treat the often fatal condition.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare, life-threatening disease characterized by the buildup of abnormal deposits of misfolded amyloid protein in the heart, causing the heart muscle to stiffen and leading to progressive heart failure. There are two sub-types of ATTR-CM: hereditary, which is caused by a mutation in the transthyretin gene and can occur in people as early as their fifties and sixties; or with no mutation and associated with aging, known as the wild-type form, which is thought to be more common and usually affects men after age 60.

ATTR-CM is often diagnosed only after symptoms have become severe when the median life expectancy is approximately two to 3.5 years. Pfizer estimates that there are about 100,000 people in the United States with ATTR-CM, and only one to two percent of those patients are diagnosed today. Pfizer estimates that globally, about 400,000 to 500,000 people might have the condition.

“ATTR-CM is not only fatal, but also significantly underdiagnosed, with some patients cycling through multiple doctors and a myriad of tests over a period of years while the disease progresses,” said Isabelle Lousada, founder and CEO of the Amyloidosis Research Consortium. “ATTR-CM is a rare disease for which more education and awareness is needed. The approval of these medicines represents an important advance for patients; however, it is equally important that we work as a community to recognize the critical importance of early diagnosis.”

Tafamidis is an oral transthyretin stabilizer that selectively binds to transthyretin, and slows the formation of amyloid that causes ATTR-CM. In late stage trials, the two oral formulations of tafamadis reduced cardiovascular mortality and the frequency of cardiovascular-related hospital stays in patients with ATTR-CM.

The FDA rejected tafamadis in 2012 as a treatment for the rare and fatal disease transthyretin amyloid polyneuropathy (ATTR-PN) in adult patients with early-stage symptomatic polyneuropathy to delay peripheral neurologic impairment. But it has won marketing approval for that condition in 40 countries. Pfizer is working to resubmit Vyndaqel for marketing approval for ATTR-PN.

Pfizer will market the drug in two formulations of tafamidis under the brand names Vyndaqel and Vyndamax, pricing them at $225,000 per year. It is hoping to reach blockbuster status within five years. The price is just half of the $450,000 list price of Alnylam Pharmaceuticals’ Onpattro and Ionis Pharmaceuticals’ Tegsedi. The rival drugs are approved to treat a slightly different rare condition called hereditary ATTR-PN, but Alnylam is working to get approval for Onpattro to treat ATTR-CM.

Vyndaqel had been granted Orphan Drug designation in the United States, European Union, and Japan, and also has Fast Track and Breakthrough Therapy designations in the United States. Vyndaqel was approved in Japan in March 2019 to treat ATTR-CM and is under review in the European Union.

Photo: Isabelle Lousada, founder and CEO of the Amyloidosis Research Consortium

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