The Food and Drug Administration said Friday that Zelnorm, the
treatment for irritable bowel syndrome, is being taken off the market because it can increase the risk of heart attacks, stroke and chest pain associated with heart disease.
Novartis agreed to pull the drug when the FDA made its request on March 29, one day after the agency met with the company to discuss Zelnorm's safety issues, said Dr. John Jenkins, director of the FDA's office of new drugs.
Despite agreeing to the FDA's request, Dr. Daniel Vasella, the chairman and CEO of Novartis, said there was no reason to withdraw the drug because there was "no causal relationship" between Zelnorm and heart problems.
"We have not proven causality," said Jenkins in a telephone press conference. However, "the data are very concerning."
Jenkins said the agency acted after reviewing a new safety analysis of Zelnorm, which was based on the pooling of data from 29 clinical trials involving more than 18,000 patients. The research showed a higher heart-damage risk for patients who received Zelnorm than those getting a placebo.
Vasella said his company will work with the FDA to determine if the drug could be resurrected to treat some patients. "We believe Zelnorm provides benefits for appropriate patients," Vasella said. If Zelnorm comes back in a restricted form, it "won't be commercially attractive," he added. "But that's not the question."
The FDA's announcement sent Novartis' shares down 89 cents, or 1.6%, to $56.
Novartis executives told analysts during the conference call that withdrawing Zelnorm would force the company to re-evaluate this year's guidance for operating earnings and net income. They didn't offer an estimate.
Zelnorm produced $488 million in U.S. sales and $71 million in other countries' sales last year. Novartis said corporate sales growth for 2007 would be "above 5%." Previously, the guidance was for "mid- to high-single digit" sales growth.
The FDA approved Zelnorm in July 2002 for the short-term treatment of women suffering from irritable bowel syndrome (IBS) plus constipation. IBS symptoms include abdominal pain, bloating and constipation.
In August 2004, the FDA cleared the drug for men and women under 65 years old with a type of chronic constipation. Approximately 500,000 people in the U.S. take Zelnorm, a Novartis spokesman said.
Novartis executives they are discussing Zelnorm's fate with foreign regulators. The company has suspended marketing in Canada, but it is keeping the drug in Switzerland for certain indications. Zelnorm, also sold as Zelmac, is available in 50 countries.
The Zelnorm decision illustrates how the FDA must balance risks against benefits, especially for a drug that provides a unique treatment.
The FDA says that in late February and early March Novartis gave the agency new analyses of 29 clinical studies comparing Zelnorm and a placebo for an assortment of gastrointestinal problems.
"The number of patients who suffered a heart attack, stroke or severe heart chest pain that can turn into a heart attack was small," the FDA said. "However, patients treated with Zelnorm had a higher chance of having any of these serious and life-threatening side effects than did those who were treated with a sugar pill."
The key issue is the concept of relative risk. The FDA said the analysis shows that 13 Zelnorm patients, or 0.1%, had "serious and life-threatening cardiovascular side effects." One of them died. Among the placebo patients, only one, or 0.01%, "had symptoms suggesting the beginning of a stroke that went away without complication."
Those results were enough to prompt the agency to issue a public health advisory. The FDA has told Novartis it would be willing to consider "limited re-introduction" of Zelnorm "if a population of patients can be identified in whom the benefits of the drug outweigh the risks."
However, any revival of Zelnorm would require review by a panel of outside experts convened by the FDA.