Tafamidis, sold under the brand names Vyndaqel and Vyndamax, is a medication used to delay disease progression in adults with certain forms of transthyretin amyloidosis. It can be used to treat both hereditary forms, familial amyloid cardiomyopathy and familial amyloid polyneuropathy, as well as wild-type transthyretin amyloidosis, which formerly was called senile systemic amyloidosis. It works by stabilizing the quaternary structure of the protein transthyretin. In people with transthyretin amyloidosis, transthyretin falls apart and forms clumps called (amyloid) that harm tissues including nerves and the heart.The U.S. Food and Drug Administration considers tafamidis to be a first-in-class medication. Medical use
Tafamidis is used to delay nerve damage in adults who have transthyretin amyloidosis with polyneuropathy, or heart disease in adults who have transthyretin amyloidosis with cardiomyopathy. It is taken by mouth.Women should not get pregnant while taking it and should not breastfeed while taking it. People with familial amyloid polyneuropathy who have received a liver transplant should not take it. Adverse effects
More than 10% of people in clinical trials had one or more of urinary tract infections, vaginal infections, upper abdominal pain, or diarrhea. Interactions
Tafamidis does not appear to interact with cytochrome P450 but it inhibits ATP-binding cassette super-family G member 2, so is likely to affect the levels of certain drugs including methotrexate, rosuvastatin, and imatinib. It also inhibits organic anion transporter 1 and organic anion transporter 3/solute carrier family 22 member 8 so is likely to interact with non-steroidal anti-inflammatory agents and other drugs that rely on those transporters.
The U.S. Food and Drug Administration rejected the application for marketing approval in 2012, on the basis that the clinical trial did not show efficacy based on a functional endpoint, and requested further clinical trials. In May 2019, the FDA approved two tafamidis preparations, Vyndaqel (tafamidis meglumine) and Vyndamax (tafamidis), for the treatment of transthyretin-mediated cardiomyopathy. The drug was approved in Japan in 2013; regulators there made the approval dependent on further clinical trials showing better evidence of efficacy.The FDA approved tafamidis meglumine based primarily on evidence from a clinical trial of 441 adult patients conducted at 60 sites in Belgium, Brazil, Canada, Czech Republic, Spain, France, Greece, Italy, Japan, Netherlands, Sweden, Great Britain, and the United States.There was one trial that evaluated the benefits and side effects of tafamidis for the treatment of transthyretin amyloidosis with cardiomyopathy, in which patients were randomly assigned to receive either tafamidis (either 20 or 80 mg) or placebo for 30 months. About 90% of patients in the trial were taking other drugs for heart failure (consistent with the standard of care).The European Medicines Agency designated tafamidis an orphan medicine and the Food and Drug Administration designated tafamidis meglumine an orphan drug. Society and culture
Legal status
Tafamidis was approved in the European Union in 2011 for the treatment of transthyretin amyloidosis with polyneuropathy, and in Japan in 2013.