The U.S. Food and Drug Administration in May approved tafamidis, a medicine invented by Scripps Research professor Jeffery Kelly, PhD, and investigator Evan Powers, PhD, for the treatment of heart disease (cardiomyopathy) caused by mutant or wild-type transthyretin aggregation in adults. 

The two formulations of the drug approved by the FDA, Vyndaqel and Vyndamax capsules, are the first FDA-approved treatments for a disease known as transthyretin amyloid cardiomyopathy, or ATTR-CM. If untreated, the disease is typically fatal within five years. 

“As the first approved therapy for this deadly disease, tafamidis represents a watershed for patients and a milestone for the development of therapies targeting amyloid diseases,” says Kelly, the Lita Annenberg Hazen Professor of Chemistry at Scripps Research. “Clinical data suggest these drugs will significantly improve the prognosis for many ATTR-CM patients.” 

Transthyretin amyloidosis is rarer than other amyloid diseases such as Alzheimer’s disease, which are caused by misfolded proteins that build up in the body’s organs and tissues. ATTR-CM is a result of transthyretin proteins that aggregate in the heart, resulting in shortness of breath, abnormal heart rhythms and chest pain. 

Vyndaqel and Vyndamax are oral medicines that bind to transthyretin, stabilizing the protein to prevent it from aggregating. Pfizer recently completed a phase 3 clinical trial of Vyndaqel in individuals with familial and sporadic ATTR-CM, demonstrating a significantly reduced risk of all-cause mortality and cardiovascular-related hospitalizations, and a 30 percent reduced risk of death compared with placebo. Based on those results, the FDA granted tafamidis a fast track designation, expediting the regulatory review process so the medicine could reach patients earlier. 

Norman Stockbridge, MD, PhD, director of the Division of Cardiovascular and Renal Drugs in the FDA’s Center for Drug Evaluation and Research, called the treatments “an important advancement in the treatment of the cardiomyopathy caused by transthyretin-mediated amyloidosis.” 

While only about 2,000 to 5,000 patients globally are diagnosed with the progressive heart disease, Pfizer estimates about 100,000 people in the United States have the condition. 

Tafamidis has also been approvedin 40 countries for familial amyloid polyneuropathy, a neurodegenerative disorder that results from transthyretin aggregation in the nervous system.