Novartis announced that the company is complying with a request from the Food and Drug Administration (FDA) to suspend US marketing and sales of Zelnorm (tegaserod maleate), a treatment for irritable bowel syndrome (IBS) with constipation and chronic constipation.

This action has been taken after Novartis notified the FDA about a retrospective analysis of data from more than 18,000 patients in the clinical trial database. This was the result of an ongoing review involving a number of health authorities including the FDA.

A small (but not statistically significant) imbalance in cases of angina pectoris was recorded and included in the US label when Zelnorm was approved in 2002. A recent analysis of the entire clinical database revealed a statistically significant imbalance in the incidence of cardiovascular ischemic events in patients taking Zelnorm/Zelmac compared to those taking placebo. These events included myocardial infarction, stroke, and unstable angina pectoris.

The data, which were reviewed by independent experts, showed that events occurred in 13 out of 11,614 patients treated with Zelnorm/Zelmac (0.11%), compared to one case in 7,031 placebo-treated patients (0.01%). All patients affected had pre-existing cardiovascular disease and/or CV risk factors.

The rate of cardiovascular ischemic events seen in Zelnorm/Zelmac-treated patients in controlled trials corresponds approximately with the expected rates for such events in the general population.

"My review of the data suggested that a causal relationship is unlikely between tegaserod and the rare cardiovascular ischemic events observed in clinical trials," said Jeffrey L. Anderson, MD, Professor of Internal Medicine at the University of Utah and Associate Chief, Cardiology Division, LDS Hospital in Salt Lake City and an independent cardiologist who reviewed the data. "Furthermore, the data did not show any consistent pattern of event type, time to event or dose relationship in tegaserod-treated patients."

Multiple studies do not suggest any constrictive effects of Zelnorm on coronary arteries.

An estimated 12 million Americans suffer from the painful and disruptive symptoms of IBS with constipation. Many have symptoms for five to 10 years, which trigger missed work-days and often prevent them from participating in everyday activities with their family and friends.

"Zelnorm/Zelmac provides unique benefits to patients by treating the multiple symptoms of abdominal pain, bloating and constipation that are associated with IBS with constipation," said James Shannon, MD, Global Head of Development at Novartis Pharma AG. "Although we have complied with the FDA's request and are collaborating with the agency, we continue to believe that Zelnorm/Zelmac provides important benefits for appropriate patients."

Nevertheless, Novartis has suspended the marketing, sales and distribution of Zelnorm in response to the FDA's request, so that public discussion and an Advisory Committee meeting can take place to determine the risks and benefits of this medicine.

Novartis and the FDA will communicate this information to physicians and patients, and will discuss the best way to continue to make Zelnorm available to appropriate patients, including through a Treatment IND. US patients taking Zelnorm are being advised to consult their physicians.

Novartis is in discussion with health authorities in other countries where Zelnorm/Zelmac is available to determine next steps. Patients outside the US who have any concerns about Zelnorm/Zelmac should discuss the situation with their healthcare professional.

Zelnorm received FDA approval for the short-term treatment of women with IBS in the US on July 24, 2002. Zelnorm also received FDA approval for the treatment of men and women less than 65 years of age with chronic idiopathic constipation in the US on August 20, 2004.

Zelnorm/Zelmac is approved for the treatment of IBS with constipation in 50 countries including Australia, Switzerland, Canada, the US, Mexico, China and Brazil.

Zelnorm/Zelmac is also approved for the treatment of chronic constipation in more than 20 countries including the US, Canada and Mexico. Novartis markets the therapy under the trademark Zelnorm (tegaserod maleate) in the US, Canada, Philippines and South Africa; and as Zelmac (tegaserod) in Switzerland, Latin America and the Asia-Pacific region.