Editor's Note: In March 2007 the FDA asked Novartis -- the maker of Zelnorm -- to pull the drug from the market because of evidence that it raises the risk of heart attacks and stroke. But in July 2007 the FDA ruled that Zelnorm may be used by some patients in critical need of the drug who do not have heart problems.
June 20, 2001 (Washington) -- The FDA decided not to approve the drug for irritable bowel syndrome, or IBS, called Zelnorm, despite an approval recommendation from the regulators' own advisory committee.
In a letter to Novartis, the manufacturer of Zelnorm, the FDA said it rejected the drug because of concerns that it may necessitate surgery to remove the gall bladder in some people, company spokeswoman Jill Pozarek tells WebMD. The FDA said that more data on the association between the drug and gall bladder removal would be required before it could be approved.
"There is no evidence that the drug would result in [gall bladder] surgery," Pozarek says. She notes that only six people out of the more than 4,500 enrolled in clinical trials of Zelnorm had to have their gall bladder removed. And one of the six was in the placebo group and did not take the drug.
IBS patients often have to undergo this type of surgery, she says, so it's difficult to attribute all the surgery cases to the drug.
However, Steven Itzkowitz, MD, chief of gastroenterology at the Mount Sinai School of Medicine, tells WebMD that although IBS patients may often have symptoms that resemble gall bladder problems, he's not aware of them undergoing gall bladder removal surgery more often than the general population.
Symptoms of IBS include abdominal pain, constipation, and/or diarrhea. The IBS Self Help Group, a patient advocacy organization, estimates that as many as 4.7 million Americans suffer from the condition and about 70% are women. IBS has no known cause, and there is no drug specifically indicated for the condition.
IBS can be so disruptive to a person's daily life that many sufferers have said they would be willing to accept the risk of gall bladder removal for a chance at relief, says Jeffrey Roberts, president and founder of the IBS Self Help Group and an IBS patient himself.
Last November, the FDA forced the IBS drug Lotronex to be taken off the market. Lotronex, which was made by Glaxo Wellcome, appeared to be a promising treatment for IBS when it was approved in February, 2000, but the FDA decided to remove it from the market after receiving complaints of serious gastrointestinal problems, including five deaths, possibly associated with the drug.
Novartis feels that the FDA may be taking a cautious approach to Zelnorm because of Lotronex, Pozarek says. Public Citizen's Health Research Group, a consumer advocacy organization, could be another factor. In March, the watchdog group filed a petition with the FDA claiming that Zelnorm increases a woman's risk for developing ovarian cysts. The drugmaker disagrees and says Public Citizen's concerns were based on incomplete information.
At a meeting last year, the FDA's own gastrointestinal drugs advisory committee said Zelnorm was effective and "did not voice any safety concerns," the agency's Jason Brodsky tells WebMD.
In addition, the FDA issued an "approvable" letter to Novartis in August, which stated that the drug could be approved, provided the company conducted one additional trial to confirm that the drug was safe and effective. Novartis conducted this trial and thought it had satisfied the FDA's concerns, Pozarek says.
"It is unusual" for the FDA not to follow the recommendation of its advisory committees, which consist of independent experts, Brodsky says, but he declined to offer further insight on why the FDA rejected Zelnorm.
Pozarek says Novartis has not decided if it will appeal the FDA's decision.