Anti-smoking pill Champix slapped blackbox warning by USFDA; may face more opposition in India

Pfizer’s Champix patents in India is already opposed by Dr Reddy’s

Champix, the anti-smoking drug from Pfizer,is likely to face more opposition in India following USFDA directive to carry a black-box warning to alert patients and doctors on serious mental health risks of the drug.

Champix,which was launched in India in February last year, is already facing a post-grant opposition on its patent in India by the local generic major Dr Reddy’s.

Pfizer’s high profile anti-smoking drug Champix contains varenicline that helps smokers stop smoking.

US FDA has ordered black box warning –the toughest warning on risks associated with a medicine — on the smoking cessation drugs Chantix (varenicline) and GSK’s Zyban (buproprion).

The safety label will highlight the alert doctors and patients to potentially severe mental health risks, including behavioral changes, depression, hostility, suicide, and suicidal thoughts, as well as warnings about allergic and skin reactions as possible risks from using these drugs.

“The risk of serious adverse events while taking these products must be weighed against the significant health benefits of quitting smoking,” said Janet Woodcock, M.D., director, the FDA’s Center for Drug Evaluation and Research, in a USFDA release.

The additional warnings from USFDA came after a review of reports submitted to the agency’s Adverse Event Reporting System since the time the products were marketed and on an analysis of information from clinical trials and scientific literature.

The analyses revealed that some who have taken Chantix and Zyban have reported experiencing unusual changes in behavior, become depressed, or had their depression worsen, and had thoughts of suicide or dying. In many cases, the problems began shortly after starting the medication and ended when the medication was stopped. However, some people continued to have symptoms after stopping the medication. Also, in a few cases, the problems began after the medication was stopped.

The FDA has been reviewing Chantix safety since 2007, after hundreds of reports of erratic, aggressive and suicidal behavior.

From May 2006 through December 2007, the FDA had received 227 domestic reports of suicidal acts, thoughts or behaviors, 397 cases of possible psychosis and 525 reports of hostility or aggression. These totals included 28 cases of suicide and 41 mentions of homicidal ideation, 60 cases of paranoia and 55 cases of hallucination. The categories were not mutually exclusive.

In the 4th quarter of 2007 varenicline accounted for 988 serious injuries in the U.S. reported to the FDA, more than any other individual drug in this time period.

Certain information on neuropsychiatric symptoms has been included in the Chantix label since November 2007 and is based on post-marketing reports.

Pfizer launched Champix in Indian market in less than two years of its launch in the US,despite serious concerns about the safety of the drug.

While launching Champix in India, Pfizer said that the company had worked with the FDA to incorporate these concerns in the labelling.

Dr Reddy’s questioned the validity of the patent in post-grant opposition filed against ‘091 patent is issued against the application No. 863/MUMNP/2003 and corresponding of Orange Book listed US Patent Nos. 6,890,927 and 7,265,119.

Post-grant opposition is a proceeding allowed in the Indian patent system to dispute the validity of a patent by a third party, which is already granted.

However, it is not necessary that Dr Reddy’s post-grant opposition against Champix should be granted by the Indian Patent Office (IPO). Recently, a similar post-grant opposition filed against Roche’s Pegasys – a pegylated interferon –by Wockhardt and some NGOs was rejected by IPO.

Pfizer’s non-nicotine smoking cessation drug Champix was priced at Rs 9,500 for a 12-week therapy in India.

Vareniclineagonist of one of the nicotinic acetylcholine receptors in the brain and nervous system,1 and currently the only marketed and approved drug with this mechanism of action.

The FDA approved varenicline in May 2006 under the brandname Chantix after granting it a priority review. Since the approval varenicline is suspected in various adverse drug event reports of including inducing suicidal thoughts. Pfizer’s anti-smoking drug Champix faces patent roadblock in India as Dr Reddy’s files post grant opposition

Among the other harmful side-effects of varenicline are serious accidents and falls, potentially lethal cardiac rhythm disturbances, severe skin reactions, acute myocardial infarction, seizures, diabetes, psychosis and aggression.

Following this, FDA issued a Public Health Advisory about one of the most marked adverse effects of varenicline, psychiatric symptoms that included “changes in behavior, agitation, suicidal ideation, attempted and completed suicide.”

Smokers usually show higher inclination to psychiatric illnesses, he said. The suicide incidents came up in the post-marketing survey and not during the clinical trials.

GlaxoSmithKline’s Zyban (buproprion) too, had been linked to adverse reactions. Similar concerns are addressed on Champix’s product insert in Europe, as well.

Champix was developed specifically to act on reducing nicotine craving and the pleasure of smoking. Research showed that the odds of quitting smoking on Champix are twice that of buproprion and four times that of placebo. Though no revenue projections were made on the drug, the product is being rolled out across 17 cities in the country, Pfizer had said.

India has a tobacco-related disease burden of over Rs 24,000 crore, and by 2010 it is estimated that over one million Indians will die of smoking-related diseases, according to Pfizer.

Champix, which is known as Chantix in US, has about 90 percent of the market for prescription smoking-cessation drugs, according to IMS Health, a health care information company. Chantix had $846 million in 2008 US sales.