FDA Approvals, Highlights, and Summaries: Cardiology 

February 27, 2020

Vyndaqel (tafamidis meglumine) and Vyndamax (tafamidis)

Tafamidis meglumine and tafamidis are indicated for cardiomyopathy caused by transthyretin-mediated amyloidosis (ATTR-CM) in adults. These are the first FDA-approved treatments for ATTR-CM. Although each product has the same active moiety, tafamidis, they are not substitutable on a milligram-to-milligram basis and their recommended doses differ.

Accumulation of amyloid fibrils composed of misfolded transthyretin protein in the heart leads to transthyretin amyloid cardiomyopathy and heart failure. Drugs that stabilize the amyloidogenic process may slow disease progression. Tafamidis is a selective stabilizer of TTR. Tafamidis binds to TTR at the thyroxine binding sites, stabilizing the tetramer and slowing dissociation into monomers, the rate-limiting step in the amyloidogenic process.

Efficacy of tafamidis was shown in a clinical trial of 441 patients randomized to receive tafamidis meglumine or a placebo. All-cause mortality and rates of cardiovascular-related hospitalizations were lower among the 264 patients who received tafamidis than among the 177 patients who received placebo (P<.001). After an average of 30 months, tafamidis was also associated with a lower rate of decline in distance for the 6-minute walk test (P<.001) and a lower rate of decline in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score (P<.001).

N Engl J Med. 2018 Sep 13;379(11):1007-1016

Additional 2019 Cardiology approvals

Vascepa (icosapent) was approved to decrease cardiovascular risk (eg, myocardial infarction, stroke, revascularization, unstable angina) as an adjunct to maximally tolerated statin therapy.

Xarelto (rivaroxaban) gained a new indication for prophylaxis of venous thromboembolism (VTE) and VTE-related death during hospitalization and at discharge in adults admitted for an acute medical illness who are at risk for thromboembolic complications from moderate or severe restricted mobility and other risk factors for VTE and not at high risk of bleeding.

Praluent (alirocumab) gained FDA approval to reduce risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with cardiovascular disease.

Invokana (canagliflozin) gained approval to reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day.

Farxiga (dapagliflozin) gained a new indication to reduce hospitalization risk for heart failure in adults with type 2 diabetes mellitus and established cardiovascular disease or multiple cardiovascular risk factors.

Conjupri (levamlodipine) is the pharmacologically active S-enantiomer of amlodipine and is indicated for hypertension in adults and children aged 6 years or older.

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