Tafamidis

An oral transthretin stabilizer, in two different formulations for adult transthretin mediated amyloid cardiomyopathy.

It selectively binds to an stabilizes transthretin, preventing dissociation of the tetramers and slowing the formation of amyloid.

A drug used to delay loss of peripheral nerve function in adults with familial amyloid polyneuropathy (FAP).

It stabilizes the correctly folded tetrameric form of the transthyretin (TTR) protein by binding in one of the two thyroxine-binding sites of the tetramer.

In people with FAP, the individual monomers fall away from the tetomer, misfold, and aggregate; the aggregates harm nerves.

Also used for the treatment of the heart disease caused by transthyretin mediated amyloidosis (ATTR-CM).

Works by stabilizing the protein, transthyretin, which is normally made up of four strands.

In FAP these strands separate and form clumps that harm nerves and invades other tissues.

Oral agent: 2 formulations

Tafamidis meglumine (Vyndaqel). Is available in 20 mg capsules and the doses for capsules once daily.

Talamidis (Vyndamax) is available and 61 mg capsules with one capsule daily.

Two preparations, tafamidis meglumine and tafamidis, were approved for the treatment of transthyretin mediated cardiomyopathy (ATT-CM).

The two preparations have the same active moiety, tafamidis, but they are not substitutable on a milligram to milligram basis.

It is used to delay impairment of peripheral nerve function in adults with familial amyloid polyneuropathy (FAP).

It is used to delay impairment of peripheral nerve function in adults with familial amyloid polyneuropathy.

Not used in pregnancy, while breast feeding and after liver transplant.

Adverse events: 10% or more have urinary tract infections, vaginal infections, upper abdominal pain, or diarrhea.

Tafamidis does not interact with cytochrome P450 enzymes.

Inhibits BCRP-likely to affect availability of drugs including methotrexate, rosuvastatin, and imatinib.

Inhibits OAT1 and OAT3 so is likely to interact with NSAIDs and other drugs that rely on those transporters.

It functions as a chaperone that stabilizes the folded tetrameric form of the transthyretin (TTR) protein by binding in one of the two thyroxine-binding sites of the tetramer.

In FAP, monomers fall away from the tetomer, misfold, and aggregate; and the aggregates harm nerves.

The maximum plasma concentration is achieved around 2 hours after dosing.

It is almost completely bound to proteins.

It is metabolized by glucuronidation and excreted via bile; in humans.

Around 59% of a dose is recovered in feces, and approximately 22% in urine.

Tafamidis reduced mortality and cardiovascular hospitalizations in both ATTRwt-CA and ATTRh-CA along with a slowing of the decline in functional capacity and quality of life.

In a randomized, double blind, placebo controlled, 30 month trial patients with hereditary or wild type ATTR-CM all-cause mortality rates were significantly lower compared to placebo: mortality 29.5% versus 42.9% with placebo and cardiovascular hospitalizations 0.48 per year versus 0.7 per year with placebo.

Adverse effects such as diarrhea and constipation or mild and discontinuation of the drug because of adverse events was less common than in the placebo group (0.8% versus 2.3%).

Annual retail price of $225,000.