Pfizer just can't seem to win with Champix/Chantix as another label change approaches

Pretty much since its launch it seems that Pfizer has been having problems with Chantix (also known as Champix outside of the US).

Launched towards the end of 2006 as the new smoking cessation drug, worldwide sale of Chantix/Champix peaked at about $280 million per quarter worldwide. Then the problems started. First, cases of neuropsychiatric adverse events began to emerge leading to a label modification warning of possible depression and suicidal ideation. These warnings were later converted to a fully blown boxed warning.

Paralleling the label changes was a slump in sales. Between Q1 2008 and Q1 2009 quarterly worldwide sales had fallen by $100 million. Pfizer's response was two-fold. Firstly, to start focusing more on the emerging markets - China and India for example where the rate of smoking is massive - approaching 50% in adult males. Secondly, Pfizer began targeting those patients at greatest risk from the effects of smoking. This included patients with COPD, those going into surgery (smoking delays wound healing) and also those with cardiovascular disease.

A good strategy on the face of things and this was borne out by data suggesting that smoking cessation with the use of Chantix improved lung function in COPD patients. Now however Pfizer has been hit again following reports that Chantix may increase the risk of heart attack in smokers.

The FDA has notified the public and physicians alike that Chantix may be associated with a small, increased risk of heart attack. This safety information will be added to the Warnings and Precautions section of the Chantix physician labeling.

The warning follows an FDA review of a randomized clinical trial of 700 smokers with cardiovascular disease who were treated with Chantix or placebo. In this trial, Chantix was effective in helping patients quit smoking and remain abstinent from smoking for as long as one year. Cardiovascular adverse events were infrequent overall, however, certain events, including heart attack, were reported more frequently in patients treated with Chantix than in patients treated with placebo.

Two questions are prompted by the most recent turn of events. What effect will this new warning have on Chantix sales and how will Pfizer respond.

As far as sales are concerned, two points must be considered. Can sales drop any more in response to adverse event fears, and secondly, patients at risk of cardiovascular disease comprise just a portion of individuals attempting to stop smoking. That is not to say that we will not see a spill over effect where otherwise healthy smokers are put off Chantix as a result of data in cardiovascular patients.

When the first series of neuropsychiatric warning came along Pfizer's reaction was to claim that the adverse events were related to smoking cessation and not to Chantix itself. This question has still not been resolved and Pfizer may well have a point although the damage was done as soon as the label was modified. We would not be surprised if the same defense came out for the cardiovascular risk. There is however one alternative explanation that may have particularly interesting consequences.

One of the most commonly used antiplatelet agents, clopidogrel (branded as Plavix), interacts with nicotine. In short, nicotine enhances the activation of clopidogrel and as a result we are left with a potential paradox.

Individuals at risk of cardiovascular events are advised to stop smoking however there is the possibility that if they are being treated with clopidogrel, smoking cessation could reduce the protection they are receiving. As a result the risk of events such as heart attacks could go up. It will be interesting to look at the data that caused the FDA to issue its warning in greater detail. What proportion of the individuals in the study were receiving clopidogrel? We shall be doing exactly that in our next issue of UpdatesPlus-Nicotinic Receptors and Smoking Cessation ( http://leaddiscovery.co.uk/updatesplus )