The pharma giant filed two new drug applications (NDAs) with the regulator covering the two forms of tafamidis – meglumine salt and free acid.
The company said that tafamidis free acid form (61mg capsule) will be under standard review while the prescription drug user fee act (PDUFA) action date for a decision on the meglumine salt form of the drug is slated to be taken by the FDA in July 2019.
ATTR-CM is a rare, fatal, and underdiagnosed condition, which results from the destabilization of a transport protein called transthyretin. The protein is made up of four identical subunits, known as tetramers.
Heart failure occurs in patients with ATTR-CM when unstable tetramers dissociate, leading to misfolded proteins that collect into amyloid fibrils and predominantly deposit in the heart.
Tafamidis is a small molecule that has been developed to selectively bind at particular sites on the transthyretin tetramer to stop destabilization of the transthyretin transport protein and formation of amyloid that causes ATTR-CM.
According to Pfizer, tafamidis is the only product to complete a phase 3 clinical trial for efficacy, safety, and tolerability in patients with the condition.
Pfizer global product development rare disease development officer Brenda Cooperstone said: “The diagnosis of ATTR-CM is often delayed, primarily because disease awareness is low and patients often present with symptoms similar to more common causes of heart failure. In fact, we believe less than one percent of patients living with this disease are currently diagnosed.
“The FDA’s filing acceptance is an encouraging step toward our goal of further raising awareness and providing a treatment option for ATTR-CM patients who are in desperate need of an approved pharmacologic therapy.”
The NDAs submission for the oral, investigational product is based on data from the phase 3 Transthyretin Amyloid Cardiomyopathy (ATTR-ACT) trial.
The late-stage study assessed the efficacy, safety, and tolerability of tafamidis meglumine against placebo for the treatment of 441 patients with ATTR-CM.
In the trial’s primary analysis, the Pfizer candidate met the primary endpoint. It showed a significant reduction in the hierarchical combination of all-cause mortality and frequency of cardiovascular-related hospitalizations in comparison to placebo through a 30-month period in patients with wild-type or hereditary ATTR-CM.