Zelnorm (tegaserod) may still be off the market, but it'll be back in the hands of select patients as the result of a new agreement between manufacturer Novartis and FDA. The drug, approved for women with Irritable Bowel Syndrome with Constipation (IBS-C) and Chronic Idiopathic Constipation (CIC), was voluntarily withdrawn from the market on March 30, after an FDA meta-analysis of 29 clinical trials showed an elevated risk of heart attack, stroke, and chest pain among in patients treated with Zelnorm compared with those given a placebo. 

The drug will now be available under a "treatment IND"--an FDA program that gives certain patients access to drugs in development, or Investigational New Drugs. "We're offering a restricted-access program for patients who are in dire need [of Zelnorm] and who have no other alternative," said Karen Sutherland, spokeswoman for Novartis. "And it's a strict protocol--it won't be available to everyone." 

To qualify, patients must contact their doctors, who are advised to call a toll-free number. Patients receive an enrollment kit, which outlines the inclusion/exclusion guidelines and emphasizes the fact that women with cardiovascular history or risks are not allowed to participate. To be included, a patient must:

Have had no satisfactory response to other available treatments and/or have had satisfactory improvement of their symptoms with prior tegaserod treatment 

A history or current diagnosis of cardiovascular ischemic disease

The presence of any cardiovascular risk factors, according to National Institutes of Health guidelines

Symptoms suggestive of cardiovascular ischemic disease

Uncompensated depression or anxiety or suicidal ideation or behavior 

FDA also made clear in a July 30 statement that doctors must determine that Zelnorm is necessary for their patients and that no other treatment options are available. Patients who qualify will receive their prescriptions free.

"We want to make clear that Zelnorm is not on the market--there's no selling or marketing of this product," Sutherland said. "We worked with FDA to develop a protocol that has been approved."

Sutherland said that Novartis received "thousands of calls" in regard to Zelnorm between the requests for access to Zelnorm and those seeking reimbursement in conjunction with a refund policy that was put into effect when Zelnorm was taken off the market. IBS is a debilitating and painful condition that can significantly impede patients' quality of life. Patients who had responded favorably to Zelnorm were advised by Novartis to seek counsel from their doctors and to contact FDA to voice their concern regarding the drug's withdrawal.

Zelnorm took in $541 million in profits last year. Pulling the drug cost Novartis $50 million. But while FDA's request was just that--a request, risk-management expert Louis Morris said not pulling the drug might have cost the company more in lost sales.

"If FDA requests that you stop marketing a drug, it's very difficult to keep selling it," he said. "Look at Avandia. FDA hasn't even requested it be withdrawn, and its sales are plummeting."

Withdrawal isn't necessarily a death sentence, either. Morris gave two examples: Fellow IBS drug Lotronex (alosetron) was pulled by Glaxo in 2000, with FDA allowing restricted marketing of the drug in 2002. Biogen Idec and Elan Pharmaceuticals pulled Tysabri (natalizumab), its monoclonal antibody for MS, in February 2005. FDA allowed restricted marketing for Tysabri in June 2006.

"I don't want to say they're being overly cautious," Morris said. "But FDA is definitely looking much more closely at safety, especially after Vioxx." That might explain all the risk managing, but the $64,000 question that keeps cropping up is, at what point does it become risk micromanaging?

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Novartis' Zelnorm is back, but only through a restricted-access program.

Zelnorm Returns--Sort Of

Obesity is contagious--sort of--argues the author of a study published in the New England Journal of Medicine last week. The study, headed up by Harvard doc Nicholas A. Christakis, says the probability that you will become obese is directly related to whether your family, friends, and friends-of-friends are obese. Obesity, in this model, is what some people have called a "social virus," a condition affecting an individual's entire social network.Some highlights of the study:

An individual's chance of becoming obese increases by 57 percent if he or she has an obese friend.

Close friends have greater impact: An individual's chance of becoming obese rises by 171 percent if a close friend is obese.

Social ties seem to spread obesity even at a distance. On the other hand, a neighbor who isn't a friend seems to have no impact.

The number of overweight or obese people in the United States is expected to top 139 million in 2010, and the global market should reach $1.5 billion in 2014. Sounds like a good incentive to market weight-loss drugs. So why the dearth of anti-obesity medications?

"Acomplia" might be a good answer. Sanofi-Aventis' weight-loss drug was set to be a blockbuster, possibly making billions in the first few years. Acomplia (rimonabant) was going to do for the obesity market what Lipitor (atorvastatin) did for the cholesterol market. But then came an unfavorable FDA advisory-committee vote in June, following which the company withdrew its NDA.

"Really, though, this is just another example of obesity: 12, therapy: 0," said Morningstar analyst Debbie Wang. She added that Acomplia's rocky path is more a sign of the market's challenges than a warning to Big Pharma.

The drugs on the market and in the pipeline just don't offer large enough results to really tap into the market. "These drugs are promising 5 to 10 percent weight loss," she said. "When you're 100 or so pounds overweight, that's just not a big enough result."

This lack of oomph follows the same pattern as anti-vice drugs. Wang said the joys of eating and smoking are not so different, and the obesity market is just following in the footsteps of the smoking-cessation market. But while there's no surgical alternative for nicotine addiction--yet--Wang said the real money in the obesity market is currently tied up in surgery.

Furthermore, those so-so weight loss results are contributing to insurers' reluctance to reimburse obesity drugs. "If someone develops a drug that works as well as surgery, I'm sure insurance companies will pony up," Wang said.

Meanwhile, Christakis' study probably won't be the kick in the gut pharma companies need. Though the mass media have tossed around the term virus, Wang said that will hardly send patients scurrying to physicians, looking for a way to protect themselves. What companies should keep an eye on, though, is the performance of GlaxoSmithKline's Alli (orlistat). "Their campaign is fascinating, we can learn a lot from it," Wang said.

A new study says obesity is like a social virus, so why is the obesity-drug market just sitting there?

Pharmaceutical Executive-08-01-2007

Zelnorm Returns--Sort Of

Anti-Obesity Drugs Struggle In Growing Market