- An experimental drug developed by Pfizer for patients with a rare and fatal heart disease cut the risk of death by 30% compared to placebo, delivering on expectations set by the pharma back in April when it had announced the Phase 3 study's success.
- The condition, known as transtheyretin amyloid (ATTR) cardiomyopathy, is caused by the build-up of misfolded protein in the heart and generally leads to death between two years and six years after diagnosis. Pfizer's drug, tafamidis, works by stabilizing the transtheyretin protein and thereby limiting deposition.
- Tafamidis could represent a competitive challenge to therapies from Alnylam Pharmaceuticals and the team of Ionis Pharmaceuticals and Akcea Therapeutics, both of which are aimed at nerve damage resulting from hereditary forms of transtheyretin amyloidosis. Pfizer expects its drug to be the first and only treatment available specifically for patients with cardiomyopathy.
Tafamidis has quickly become a key asset in Pfizer's plans to build its presence in rare disease.
Expectations for the drug were low until release of topline results from a Phase 3 study earlier this year — a success that one analyst called a "rare late-stage pipeline surprise."
The detailed data released Monday in the New England Journal of Medicine firm up those prospects, delivering a significant risk reduction in all-cause mortality versus placebo. Treatment with tafamidis also led to a 32% drop in the risk of cardiovascular-related hospitalizations.
The mortality benefit only emerged after 18 months, however, which could reflect time needed to change the course of disease pathology, wrote C. Cristina Quarta and Scott Solomon, from the University College London and Brigham and Women's Hospital respectively, in a related New England Journal of Medicine editorial published Monday.
Study investigators also reported tafamidis slowed declines in distance walked during a 6-minute test, a clinical measure aimed at capturing functional capacity.
Pfizer tested tafamidis in patients with cardiomyopathy caused by mutations of the transtheyretin gene as well as by wild-type transtheyretin protein. While subgroup results for patients with wild-type ATTR were statistically significant for a benefit on all-cause mortality, tafamidis did not clear the bar for significance among patients with mutant ATTR.
The pharma, though, said the study was not designed to test for significance within each subgroup, only the broader pooled analysis. Benefit on all-cause mortality directionally favored the tafamidis group among mutant ATTR patients.
Pfizer is bullish on tafamidis' prospects, listing the drug as one of 15 potential blockbuster therapies, and believes its data sets the bar for others to clear in ATTR cardiomyopathy.
"To run such a study takes more than four years, so we think that tafamidis will have an opportunity, pending regulatory dialogue, to be a real first-in-class drug for severe patient needs," said Pfizer's R&D chief Mikael Dolsten on an earnings call last month.
Earlier this month, the Food and Drug Administration approved Alnylam's Onpattro (patisiran) for neuropathy tied to transtheyretin amyloidosis, and Ionis and Akcea expect to win an OK for their drug in October. Both will likely aim to expand into cardiomyopathies resulted to the disease, making Pfizer's tafamidis a potential challenger.
(While Alnylam reported exploratory cardiac data from Onpattro's pivotal study, the results were not included on the drug's label.)
Investors, however, appear to be bullish on the competitive balance, sending shares in both Alnylam and Ionis sharply higher Monday morning. Pfizer stock, on the other hand, fell by a little more than 2% after market open.