FDA clears Pfizer drugs Vyndaqel, Vyndamax for transthyretin amyloid cardiomyopathy

Pfizer announced Monday that the FDA approved Vyndaqel (tafamidis meglumine) and Vyndamax (tafamidis) to treat cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalisation. The company noted that both drugs are oral formulations of the transthyretin stabiliser tafamidis, as well as the first medicines approved in the US to treat ATTR-CM. 

Norman Stockbridge, director of the Division of Cardiovascular and Renal Drugs in the FDA's Center for Drug Evaluation and Research, commented "the treatments we're approving today are an important advancement in the treatment of the cardiomyopathy caused by transthyretin-mediated amyloidosis." The agency had previously declined to approve Vyndaqel in 2012 for use in adults with transthyretin familial amyloid polyneuropathy (TTR-FAP) and directed Pfizer to complete a second efficacy study. 

The approvals of Vyndaqel, taken as four capsules once-daily, and Vyndamax, which is taken as a single capsule, were supported by data from the Phase III ATTR-ACT cardiovascular outcomes trial. Results unveiled last August showed that Vyndaqel significantly reduced the risk of all-cause mortality by 30 percent versus placebo, while the frequency of cardiovascular-related hospitalisation was slashed by 32 percent. 

Pfizer has set a list price of $225 000 per year for the treatments. Paul Levesque, global head of Pfizer's rare disease unit, commented "there were three factors we took into consideration on this price: the transformative nature of this compound, the population...and the third would be our capacity to ramp up diagnosis over time." He noted that quickly reaching over 30 percent of a rare disease population with a new drug is very rare.

Commenting on the news, Stifel analyst Paul Matteis said the list price was at the "high end of expectations," although it is half the average list price of Alnylam Pharmaceuticals' Onpattro (patisiran) and Akcea Therapeutics' Tegsedi (inotersen). The analyst indicated that a lower price for Vyndaqel would have raised concerns that insurers might have positioned the drug as the preferred treatment for hereditary ATTR patients "across the board, regardless of phenotype." 

Matteis also predicted that Vyndaqel will "dominate the pure cardiomyopathy segment of hereditary ATTR…limiting the size of the pie" in the near term for Onpattro and Tegsedi. However, he suggested that patients with both nerve and heart problems "are more likely to be a battleground area," where a case could be made for using the drug along with either Onpattro or Tegsedi. Patients whose primary symptoms are heart-related will likely receive Vyndaqel, while those with neuropathy will probably be prescribed one of the other therapies, Matteis added. Analysts expect sales of the Pfizer drugs to surpass $1 billion in 2024. 

The FDA previously granted fast track and breakthrough therapy status to Vyndaqel for ATTR-CM. Vyndaqel has also been authorised in Europe for the treatment of TTR-FAP in adults with stage 1 symptomatic polyneuropathy. 

Meanwhile, Alnylam plans to start the Phase III APOLLO-B study in mid-2019 evaluating Onpattro in hereditary and wild-type ATTR amyloidosis patients with cardiomyopathy. The company is also developing vutrisiran, which would be administered via subcutaneous injection, for patients with both hereditary and wild-type ATTR. Akcea is developing a drug for hereditary and wild-type ATTR as well.

For related analysis, see ViewPoints: Pfizer takes a niche approach for Vyndaqel launch. See also ViewPoints: TTR showdown begins well ahead of tafamidis approval.

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