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FDA OKs Pfizer Rare Disease Drug, Sets Up Battle With Alnylam, Akcea

Xconomy New York — 

[Updated 5/6/19, 9:20 am ET. See below.] A year ago, there were no FDA-approved medicines available for US patients with the debilitating rare genetic disease transthyretin amyloidosis (ATTR). Things have changed fast, however: With the FDA’s decision to approve a drug from Pfizer this morning, patients now have three options to choose from.

The FDA approved two oral formulations of the Pfizer (NYSE: PFE) drug tafamidis, to be sold as Vyndaqel and Vyndamax. The drug has been approved specifically to treat the potentially deadly heart problems faced by patients with both the hereditary and “wild-type” forms of ATTR, the latter of which develops over time. It will have a list price of $225,000 per patient, per year, according to a Reuters report. The approval came early—the FDA’s decision was expected to happen by July.

People who have ATTR make a mutated version of the protein transthyretin, which builds up in misfolded clumps, causing damage to a variety of tissues around the body. Some patients suffer just the nerve damage, which starts with numbness in the toes, then feet, and moves upwards. Others suffer a corrosion of the heart’s wiring that can lead to heart failure and death. Most patients have elements of both issues. New York-based Pfizer estimates that about 100,000 ATTR patients in the US have heart problems, and only one to two percent of them are diagnosed today.

For years, the only available treatments in the US were liver transplants or diflunisal, a generic anti-inflammatory drug used off-label to “stabilize” the TTR protein and slow the progressive nerve damage. But things changed in 2018 when the FDA approved two drugs: patisiran (Onpattro), from Cambridge, MA-based Alnylam Pharmaceuticals (NASDAQ: ALNY), and inotersen (Tegsedi), from Boston-based Akcea Therapeutics (NASDAQ: AKCA). Both give patients the chance to halt the progression of their nerve damage—and in some cases, improve nerve function.

Pfizer’s drug is similar to diflunisal, in that it is meant to stabilize TTR, and it has a checkered past. Although tafamidis has been approved in Europe as a treatment for the neuropathy that ATTR patients face, the FDA rejected it in 2012. Pfizer, however, has since run studies showing that the drug cut the risk of death and cardiac-related hospitalization for patients with both hereditary and wild-type ATTR.

Neither patisiran nor inotersen have definitively shown that they can do the same. They are currently only approved for neuropathy in patients with hereditary ATTR. Alnylam’s drug generated $26.3 million in sales in the first quarter of 2019; Akcea has yet to report its first-quarter results.

[Updated with analyst comments—Eds.] At $225,000 per year, Pfizer has priced its drug at half the $450,000 average list price of both patisiran and inotersen. Still, the price tag comes at the “high end of expectations,” wrote Stifel analyst Paul Matteis. If tafamidis had been priced lower, it would’ve raised concerns that insurers might have positioned the drug as the preferred treatment for hereditary ATTR patients “across the board, regardless of phenotype,” he wrote.

It’s important to note roughly two-thirds of all ATTR patients have both nerve and heart damage, which means there could be an overlapping group of US patients eligible for patisiran, inotersen, and tafamidis. And both Alnylam and Akcea aim to broaden the use of their respective franchises. Alnylam, for instance, aims to start a Phase 3 study this year testing patisiran in ATTR patients with heart problems. It has another ATTR drug, vutrisiran, in development that would be administered via subcutaneous injection. That drug is being tested in patients with both hereditary and wild-type ATTR. Akcea, a spinout of Carlsbad, CA-based Ionis Pharmaceuticals (NASDAQ: IONS), is also developing a drug for hereditary and wild-type ATTR.

Matteis expects tafamidis “to dominate the pure cardiomyopathy segment of hereditary ATTR…limiting the size of the pie” in the near term for the Alnylam and Akcea drugs. Patients with both nerve and heart problems “are more likely to be a battleground area” where a case could be made for using tafamidis along with either patisiran or inotersen. Those whose primary symptoms are heart-related will likely end up on tafamidis, while those with debilitating neuropathy will likely end up on one of the other drugs, Matteis wrote.