As we reported on Tuesday, the FDA approved tafamidis meglumine (brand name: Vynaqel, from Pfizer) and tafamidis (brand name: Vyndamax from Pfizer) early on 5/6/2019 for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. Transthyretin-mediated amyloidosis is a rare, debilitating and often fatal genetic disease characterized by the accumulation of abnormal amyloid protein in peripheral nerves, the heart and other organs. Tafamidis meglumine had been granted a priority review with a July 2019 PDUFA date and the free acid of tafamidis had a standard review with a November 2019 PDUFA date.
In the 30-month, 441 patient, Phase III, ATTR-ACT trial, tafamidis reduced all-cause mortality (30% vs 43%) compared to placebo. Tafamidis also reduced cardiovascular-related hospitalizations, decline in 6-minute walk test and decline in the Kansas City Cardiomyopathy Questionnaire–Overall Summary that measures health status. Tafamidis was dose at both 20 mg and 80 mg per day. The two doses were not compared, instead the authors combined the results when comparing the drug to placebo.
The recommended dosage in the approved labeling for tafamidis meglumine is four 20 mg capsules once daily (80 mg total dose). The recommended dose for tafamidis is one 61 mg capsule taken once-daily. The annual WAC for both drugs is $225,000. Tafamidis was approved in EU for Transthyretin Familial Amyloid Polyneuropathy (hTTR-FAP) in 2011. In Europe it is dosed at 20 mg per day to treat transthyretin familial amyloid polyneuropathy (hTTR-FAP). The FDA rejected the drug in 2012 for the treatment of hTTR-FAP because of a failed U.S. trial and requested an additional clinical trial. Pfizer
Tafamidis reduces the formation of TTR amyloid by stabilizing the TTR tetramers that contain mutant amyloid, which prevents the release of amyloidogenic monomers and joins two other drugs which were approved in 2018 that decrease TTR synthesis: patisiran and inotersen.
Patisiran (Onpattro) and inotersen (Tegsedi) were approved for the treatment of hereditary hTTR-FAP. Inotersen is administered as a weekly subcutaneous injection and has a black box warning for thrombocytopenia and glomerulonephritis. Patisiran is given as an intravenous infusion every three weeks.
Both patisiran and inotersen have an annual WAC price of $450,000. The Institute for Clinical and Economic Review (ICER) estimated the discounted price to be $345,000 per year. ICER’s analysis found that compared to best supportive care inotersen would need to cost $96,103 and patisiran would need to cost $200,000 to reach a quality-adjusted life year (QALY) of $500,000/ To reach a QALY of $150,000, inotersen would need to cost $25,000 and patisiran would need to cost $46,000.
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