September 13, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Even if you haven’t paid much attention to them, most people have heard the disclaimer on TV ads for Pfizer ’s Chantix that the drug might cause “potential changes in behavior, depressed mood and suicidal thoughts.” For at least two years, Pfizer has been trying to get the U.S. Food and Drug Administration (FDA) to let them modify those statements and eliminate the “black box” warning on the product. In a report released this week by the FDA, staffers who reviewed the company’s clinical trial of Chantix, raised questions about how Pfizer researchers evaluated and recorded neuropsychiatric events.
“The trial was designed in a well-intentioned attempt to capture somewhat ill-defined and complex neuropsychiatric phenomena,” the report stated. “However, many problems in the implementation were apparent upon review of the collected data.”
Chantix is a drug used to help stop smoking. The trial in question was partially designed to evaluate 16 different categories of neuropsychiatric side effects. Those 16 were further split into 261 different medical terms. Examples include “agitation,” which could also be defined as “restlessness” or “disturbance in attention.”
The study compared Chantix to GlaxoSmithKline ’s Zyban versus a placebo or nicotine patch in smokers with and without a history of psychiatric disorders. Pfizer’s interpretation of the study found there were minimal side effects, but the FDA did not agree, hence the warning and verbiage.
The FDA argues that there were inconsistencies in the data collection and in how researchers described the severity of some of the side effects.
“Ultimately, what was reported as an adverse event,” James Rusnak, chief development officer of Pfizer’s cardiovascular metabolic unit told Reuters, “was determined based upon the investigator’s local determination of the subject presenting in front of them.”
In addition, Rusnak pointed out that the study was conducted at multiple centers, so any systemic subjectivity on the part of investigators was unlikely. It was also a blinded study, so the researchers didn’t know whether the participants were on Chantix, Zyban, placebo or a patch.
European regulators dropped the warning label in May, where the drug is marketed as Champix. Outside experts will hold a meeting Wednesday in Silver Spring, Maryland, to provide the FDA with a recommendation on changes to the warnings for Chantix and Zyban.
In 2015, Chantix brought in $671 million in sales. The drug’s patent expires in four years.
Another topic raised in the report is researchers who received $25,000 speaking fees to talk about Chantix, and whether those researchers underreported side effects. This seems unlikely, as Rusnak mentioned earlier, because the researchers didn’t know who was actually on the drug.
Pfizer published the results of this study earlier this year in the medical journal Lancet, which cites that Chantix and Zyban do not increase the risk of suicide. “The study found that,” STAT writes, “among patients already diagnosed with a psychiatric disorder, 6.5 percent of those on Chantix and 6.7 percent on Zyban had a neuropsychiatric side effect, compared to 4.9 percent on a placebo. Of those not diagnosed with a psychiatric disorder, 1.3 percent of those given Chantix experienced a neuropsychiatric side effect compared to 2.2 percent on Zyban and 2.4 percent on a placebo.”
