FDA Reviewer Slams Pfizer Drug as Ineffective

FDA Reviewer Slams Pfizer Drug as Ineffective

May 25th, 2012 // 12:37 pm @ jmpickett

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In late 2010, Pfizer trumpeted the purchase of a small, privately held drugmaker called FoldRx Pharmaceuticals, which developed its own discovery platform technology and was completing testing for it lead candidate. Called Tafamidis, the medicine is designed to treat familial amyloid polyneuropathy, a rare and progressively fatal genetic neurodegenerative disease for which liver transplant has been the only available option for treatment.

“This transaction will add another important component to the growing portfolio of innovative in-line and investigational medicines for orphan and rare diseases within Pfizer’s Specialty Care Business, and will complement the current and planned future research and clinical development taking place in Pfizer’s Specialty Care Neuroscience disease area,” Geno Germano, president and general manager of the Pfizer Specialty Care Business Unit, said in a statement (see this).

But 18 months later, the acquisition is looking less exciting. An FDA panel will review the drug tomorrow and agency briefing documents do not offer a good prognosis. In an unusual move, an FDA medical reviewer comes out and suggests the drug should not be approved right now because it simply does not measure up. “I recommend a Complete Response action, based on inadequate evidence of effectiveness,” writes Devanand Jillapalli, an FDA staffer in the division of neurology products.

Why? The approval comes down to findings in a single controlled trial – a double-blind, randomized, placebo-controlled, parallel group, multi-national study in which patients with FAP were randomized to receive either the drug once a day or placebo. But the effects of the drugs were seen in patients in just one study site that enrolled 58 percent of patients. Meanwhile, neither of two primary outcomes met the protocol-specified standard for statistical significance, although Pfizer performed numerous sensitivity analyses to support the conclusion the study can be considered positive.

This study, Jillapalli writes, has important weaknesses and there was “minimal evidence” of efficacy in the other seven study sites. “Given that (the study) is the sole controlled trial submitted, and given the issues raised about the results, we are very interested to hear the committee’s thoughts on whether or not this study provides the sort of robust data that would ordinarily be required to support the ‘single study’ definition of substantial evidence of effectiveness for a clinical outcome,” write division director Rusty Katz (here is the briefing document). Tafamidis has fast track designation in the US, by the way.

Despite the appearance of a possible setback, the drug is expected to be a minor product for the drugmaker, given that the FDA estimates only 5,000 to 10,000 people worldwide are affected by the affliction. Of course, Pfizer would have proceeded anyway, since the FoldRx acquisition involved proprietary technology used to target diseases caused by so-called protein misfolding. And in doing so, the drugmaker can also point its pursuit of a treatment for a rare disease. Tafamidis is already approved in Europe.