Zelnorm Returns--Sort Of

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with Irritable Bowel Syndrome with Constipation (IBS-C) and Chronic Idiopathic Constipation (CIC), was voluntarily withdrawn from the market on March 30, after an FDA meta-analysis of 29 clinical trials showed an elevated risk of heart attack, stroke, and chest pain among in patients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:

• Be a woman under the age of 55

• Currently suffer from IBS-C

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

A patient will be excluded if she has:

• 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?