The FDA raised some questions about Pfizer’s Chantix data up for review at an advisory committee meeting today. That’s not unusual; the agency often sets out its reservations ahead of those panel discussions.
But this time, on page 63 of the review documents, FDA reviewers flagged something quite unusual. They suggested that Pfizer’s financial ties to doctors participating in the study may have biased the data.
Financial disclosures showed that investigators at 32 trial sites received speaking fees from Pfizer. At two particular sites, the doctors studying the drug collected “multiple” honoraria for speaking engagements, the documents state. And at 12 of those 32 sites, the investigators were paid specifically for speaking about Chantix.
The sites where Pfizer had paid speaking and other fees reported fewer neuropsychiatric side effects than those that did not, an agency analysis found.
That’s potentially significant, because the study in question is all about those side effects. It’s part of Pfizer’s case to remove a black-box warning on Chantix’s official label. The warning, which highlights potential problems such as suicidal thoughts and behavior changes, has been on the med since 2009, and analysts figure it has limited uptake of a drug that was initially expected to soar to blockbuster status.
But it's important to point out that the agency found only small numerical differences, and the reviewers noted that they might have been innocent enough. Indeed, the FDA's own sensitivity analysis--in which it excluded data from those 32 sites--delivered results consistent with the overall outcome of the trial.
And Pfizer pointed out that the study was a triple-dummy, blinded trial. It compared Chantix with the GlaxoSmithKline med Zyban, placebo, and nicotine therapy. "Potential bias at a particular study site would be equally distributed across all four treatment arms," the company said in an email to FiercePharma.
Whether the advisory committee itself considers the payments as an issue will be clear Wednesday as it meets to discuss the study and the drug’s warning language.
Pfizer tried and failed in 2014 to persuade the FDA to remove the warning. The agency instead added cautionary language about combining Chantix with alcohol.
At the time, the FDA did add information about several studies that looked at the risk of neuropsychiatric effects with Chantix, including observational studies and Pfizer's analyses of clinical trial data. The studies didn't show an increased risk of neuropsychiatric side effects, the agency pointed out.
"[H]owever, they did not examine all types of neuropsychiatric side effects, and they had limitations that prevented us from drawing reliable conclusions," the agency says.
Meanwhile, Pfizer has been trying to augment its case for the drug by conducting follow-up trials about its benefits, as well as the studies it’s been conducting on Chantix’s risks, on its own and at the FDA’s behest.
Earlier this year, European regulators did pull Chantix's black triangle, which indicates that additional safety monitoring is required. That move was based on the same study data FDA is considering now. Data from the trial was also added to the official European label.
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Editor's note: This story was updated with comments from Pfizer. It also corrected numbers that were wrong in the FDA's review documents. Pfizer's most recent advisory committee hearing was in 2014, not 2015, as previously stated.