Pfizer drug gets speedy FDA review for rare heart failure complication

Pfizer has been awarded a breakthrough designation from the FDA for tafamidis as a treatment for the rare disease transthyretin cardiomyopathy – suggesting its marathon effort to get the drug to the US market is gaining traction.

Transthyretin cardiomyopathy is a fatal and underdiagnosed condition associated with progressive heart failure, with no FDA-approved treatments, and tafamidis chalked up a comprehensive win in its phase III trials programme with a significant impact on both all-cause mortality and cardiovascular hospitalisation, the main outcome measures.

The average life expectancy for people with transthyretin cardiomyopathy is three to five years from diagnosis, says Pfizer, which also got fast-track status for tafamidis last year.

The drug was the centrepiece of Pfizer’s acquisition of FoldRx Pharma in 2010 and was submitted for approval in the US for transthyretin familial amyloid polyneuropathy (TTR-FAP) shortly afterwards, only to be turned down by the regulator after it decided there was not enough evidence for a substantive review.

It did get the green light in Europe, however, where it is sold as Vyndaquel as a treatment to delay neurologic damage in patients with hereditary TTR amyloidosis (ATTR), the umbrella term for a range of disorders with different phenotypes of symptoms. Since then, tafamidis has also been approved in other markets including Japan, Mexico, Argentina, Israel, South Korea and Brazil.

Pfizer tried again in the US a year later, and picked up an FDA advisory committee recommendation for approval in TTR-FAP before the agency sent the company a complete response letter asking for additional clinical trials.

Pfizer chief executive Ian Read said on the company’s first-quarter results call that tafamidis has “huge potential” and could become a blockbuster product, along with other late-stage pipeline products including the company’s Clostridium difficile vaccine and nerve growth factor-targeting tanezumab for severe pain.

There is potential competition in the offing however from Alnylam's Sanofi-partnered patisiran, because while that company is focused more on polyneuropathy than cardiomyopathy in its clinical trials, it has reported some effect on cardiovascular outcomes including cardiomyopathy. Another rival is Ionis with its inotersen candidate, which showed efficacy against polyneuropathy in a phase III trial reported last year.

Pfizer is seen very much as the disruptive element in the TTR-FAP market, a third force in a market that until last year looked like a two-way fight, and shares in both Alnylam and Ionis took a dive when it reported its phase III data earlier this year.

Analysts have suggested that cardiomyopathy is seen in around a quarter of TTR amyloidosis patients, so Pfizer will only cross over with its rivals in a subset of patients. That’s not however stopping some analysts giving the drug $1bn-plus sales projections.

A further wrinkle is that Alnylam’s trials only enrolled subjects with hereditary ATTR, while Pfizer’s studies included both hereditary and ‘wild-type’ TTR cardiomyopathy. Added to that, Pfizer’s drug can be given orally, while patisiran and inotersen both require injection.

Tafamidis is part of a portfolio of rare disease therapies at Pfizer, along with two Duchenne muscular dystrophy drugs, a sickle cell programme and gene therapy assets, that Read said gives the company “critical mass” in the sector.