IHS Global Insight Perspective | |
Significance | A John Hopkins University (US) study has linked Pfizer (US)'s Champix/Chantix (varenicline) to a 72% increase in risk of hospitalisation due to serious cardiovascular events in smokers. Most importantly, the study's conclusion points out that priority review for the drug was granted with limited safety data at time of approval, and that Champix's initial safety signal relating to cardiovascular events was not followed up adequately. |
Implications | The results put further pressure on the drug's safety profile, with the US FDA expected to examine the study's evaluations. Champix is already labelled with a "black box" warning over mental health risk, such as behavioural changes, suicide and depression. |
Outlook | The drug is increasingly popular as a preferred treatment worldwide, with several countries implementing smoking-cessation campaigns. If the FDA decides to issue further safety notifications for the drug, it could adversely affect potency vis a vis its risks globally. |
A study published in the latest issue of the Canadian Medical Association Journal (CMAJ) has raked up doubts over the safety profile of the smoking-cessation drug Champix/Chantix (varenicline), developed and marketed by US pharma major Pfizer. The study was conducted by researchers from the Johns Hopkins University School of Medicine (US), the University of East Anglia (UK) and the Wake Forest University (US) with part-funding from the National Center for Research Resources (NCRR), a unit of the US National Institutes of Health (NIH). The methodology involves meta analyses of 14 selected double-blind randomised clinical trials with at least one week of follow up evaluating varenicline as compared to a placebo in tobacco users reporting cardiovascular events. The conclusion of the study was that varenicline is associated with a "significantly increased risk of serious adverse cardiovascular events"—1.06% (52/4908) in the varenicline arm and 0.82% (27/3308) in the placebo arm. The study also said that the possible drug mechanisms associated with cardiovascular conditions include "action of the drug at the [alpha]-7 receptor in the brainstem or, similar to nicotine, a protombotic effect''.
The study can be accessed in full here (source: Pharmalot.com).
Pfizer's Response
The pharma major has responded to the conclusions of the study by reaffirming the effectiveness of the drug and its benefit/risk profile. The firm has, however, questioned the reliability of the meta-analysis, noting the appropriateness of the risk measure used or composite endpoint which combines events that do not share a common biological cause. Furthermore, it has highlighted the small number of events studied as well as cast doubt over the manner in which the events were classified and counted. Significantly, the firm said it is discussing with the FDA a protocol to conduct its own meta-analysis to further evaluate the cardiovascular safety of the drug. Champix/Chantix is one of the firm's top drugs with a global approval reach of 99 countries, and prescribed to 13 million patients. The drug garnered sales of USD775 million in 2010.
Outlook and Implications
The study's conclusions will affect the profile of Champix/Chantix, but to what extent will depend on the FDA's review of the meta-analyses conducted by Pfizer comparing it to the latest Johns Hopkins University study. Clearly, the results cast a negative light on the safety-profile of the drug, which is increasingly being used as a popular choice for smoking cessation in several countries where quit smoking campaigns have been initiated. The study raises two important questions which will be debated by the FDA in the short term. One, of course, is the safety profile of the drug and whether the latest study's methodology is representative of a small number of events or not. The drug already contains a "black box" warning following an FDA review in 2009 which highlights potential risks towards neuropsychiatry events such as suicidal thoughts, behavioural changes and depression among others in users. Hence, the addition of cardiovascular risk tied to the warning will affect the drug's prospects, but whether the benefit/risk profile is sufficiently tilted towards the negative will remain to be seen.
The other issue raised by the study is that of the FDA's accelerated approval procedure. It points out that the FDA had identified the cardiovascular adverse events linked to the drug at the time of review in 2006. But additional studies to establish a clear picture over the cardio effects was not followed up by the regulator. The FDA explained that at the time close inspection of the drug's cardio effects was followed up, but conflicting results had culminated in no changes to the label (source: Bloomberg). For Pfizer, the focus will be on taking into account the limitations of this latest study and creating a new one wherein the meta-analyses would potentially support the benefits of the drug outweighing risks.