Pfizer Defends Beleaguered Varenicline (Chantix)

By Todd Neale
NEW YORK, 08 june 2008-- With its antismoking drug varenicline (Chantix) under a cloud for allegedly sparking suicidal behavior and ideation, Pfizer took its case to the press today, defending the agent as contributing far more benefit than potential harm.
Apparently stung by an FDA warning, followed by a ban of use of the drug by pilots and flight controllers issued by the Federal Aviation Administration, the company invited journalists to what it called a roundtable discussion to set the record straight.
At the session, three of Pfizer's senior officers sought to explain the occurrence of the adverse events, compare them with the benefits of quitting smoking, and explain how Pfizer is responding. Also attending was a clinical investigator who took part in a phase III trial of varenicline.
In February, the FDA warned of mood swings and suicidal behavior in patients taking varenicline, but maintained that it was effective as a medication for quitting smoking. (See: FDA Warns of Mood Swings and Suicides With Smoking-Cessation Drug)
The drug works by partially blocking the alpha4-beta2 nicotinic acetylcholine receptor, which releases dopamine when nicotine binds to it. Small amounts of dopamine are released when varenicline binds to the receptor, but substantially less than with nicotine.
The company officers insisted that the drug, approved by the FDA in 2006, is not only effective but safe. "The question is, 'Do we believe that the benefit-risk profile of Chantix is positive,' and I would say absolutely it is," Gretchen Dieck, Ph.D., Pfizer's senior vice president of safety and risk management, said.
"It is far better to get patients off cigarettes," she continued. "We can manage some of the risks that we are seeing that are either due to nicotine withdrawal, underlying disease, or perhaps Chantix."
Ponni Subbiah, M.D., a vice president of Pfizer Medical, said that some of the ongoing studies Pfizer is conducting involved adolescents, pregnant women, and patients with schizophrenia, emphysema and chronic obstructive pulmonary disease, and heart disease. Results from these studies will be published, or at least posted on the company's Web site, within the next few years.
A detailed analysis of neuropsychiatric adverse events linked to use of varenicline will be published later this year, she said.
The FAA ban last month was based on a report released by the Institute for Safe Medication Practices detailing a high number of serious injuries in patients taking the drug. (See: Varenicline (Chantix) Off the Table for Pilots and Controllers)
"The fact that the FAA has done this is not that unexpected," Joseph Feczko, M.D., chief medical officer of Pfizer, said, citing the wide range of drugs the agency also bans, including antidepressants, anxiolytics, diabetes medications, and some antihistamines.
Dr. Dieck pointed out that the institute's report was not peer-reviewed or published in a peer-reviewed journal.
She added that the report listed tallies of adverse events, but without knowing what counts were expected. "The expected number could be far greater than the observed reporting rate," she said.
David Gonzales, Ph.D., of the Oregon Health & Science University in Portland, and lead author for one of the pivotal phase III trials considered during FDA approval of varenicline, said that none of the neuropsychiatric adverse events he observed raised any red flags. He attended the roundtable discussion but not as a panelist.
"We see depressed mood and depression as being very common," he said, "so we didn't see anything in the trials that would cause us to think there was something unique going on with Chantix."
He noted, however, that his group screened patients entering the trial for serious psychiatric disorders and excluded them so they could determine the effect of the drug independent from the history of the patient.
He added that it is difficult to tease out whether the adverse events in trials are caused by the drug or by the withdrawal from nicotine. Many individuals use cigarettes, he asserted, to self-regulate mood, he said, and removing their drug of choice will likely cause some psychiatric symptoms.
Furthermore, he said, events reported outside the clinical trial setting do not have the detailed follow-up that a controlled regimen allows.
"With psychiatric issues, often times with the patient who's making the report you don't have it confirmed by psychiatrists or psychologists," he said.
In closing remarks, Dr. Fecsko reiterated what he believes to be a benefit for quitting smoking with varenicline. "We feel in Chantix we've discovered and developed a significant treatment option for those individuals who need it," he said.