FDA Responds to Pfizer’s Tafamidis New Drug Application

FDA requests second study to establish evidence of effectiveness

/ Author:  / Reviewed by: Natasha Levin

Pfizer Inc. announced that it has received a Complete Response Letter from the US Food and Drug Administration (FDA) on its New Drug Application (NDA) for tafamidis meglumine.

The Agency is requesting the completion of a second efficacy study to establish substantial evidence of effectiveness prior to an approval. The Agency has also asked for additional information on the data within the current tafamidis NDA. Pfizer will work with the FDA to address the content of the letter. Tafamidis is a novel, investigational medication for the treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP) in adult patients with symptomatic polyneuropathy to delay neurologic impairment.

The European Commission (EC) approved Vyndaqel (tafamidis) for the treatment of TTR-FAP in adult patients with stage 1 symptomatic polyneuropathy on November 16, 2011. In the US, there is no FDA-approved treatment for TTR-FAP.

“TTR-FAP is a relentless and debilitating disease. We understand the urgent need within the patient community and stand firmly behind this innovative medicine,” said Dr. Yvonne Greenstreet, senior vice president and head of Medicines Development Group for Pfizer's Specialty Care Business Unit. “It is our intention to request a meeting as soon as possible with the Agency in order to discuss a potential path forward.”

TTR-FAP is a rare, progressive and fatal neurodegenerative disease that affects approximately 8,000 patients worldwide. Because it is a hereditary disease, family members may also be at risk for developing the disease. In the US, a non-endemic region, the incidence is estimated to be about 1 in 100,000, impacting approximately 3,000 people.

About Transthyretin Familial Amyloid Polyneuropathy (TTR-FAP)

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare and fatal neurodegenerative disease, primarily caused by a genetic mutation of the transthyretin (TTR) gene. In TTR-FAP, transthyretin destabilization leads to misfolded proteins that form amyloid fibrils in the peripheral and autonomic nerves, as well as other organs including the GI tract, kidneys and heart. Patients with TTR-FAP experience significantly diminished quality of life due to symptoms including polyneuropathy characterized by sensory loss, pain and weakness in the lower limbs; as well as severe impairment of the autonomic nervous system commonly manifesting as erectile dysfunction, alternating diarrhea and constipation, unintentional weight loss, orthostatic hypotension, urinary incontinence, urinary retention and delayed gastric emptying. As the disease progresses, patients often lose the ability to walk, needing wheelchair assistance, and eventually become bedridden and unable to care for themselves. TTR-FAP typically occurs during active adult years with onset as early as the 30s, followed by disease progression that may reach the terminal stage in approximately 10 years on average.

About Tafamidis

Tafamidis is a novel, selective stabilizer of the transthyretin protein approved in November 2011 by the European Commission (the trade name in the European Union and proposed trade name in the US is Vyndaqel). It is indicated in the European Union for the treatment of TTR amyloidosis in adult patients with stage 1 symptomatic polyneuropathy to delay peripheral neurologic impairment.

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Review Date: 
July 18, 2012