Approval Recommended for Use of Zelnorm in Chronic Constipation by FDA Advisory Committee

ROCKVILLE, Md. -- Novartis Pharmaceuticals Corporation announced that Zelnorm® (tegaserod maleate) was recommended for approval for the treatment of chronic constipation (CC) by the Gastrointestinal Drugs Advisory Committee to the U.S. Food and Drug Administration (FDA). The committee’s recommendation was subject to specific labeling regarding age and gender. Novartis will work with the FDA to address the issues raised by the committee.

The supplemental new drug application (sNDA) for Zelnorm for chronic constipation was filed in October 2003. The FDA generally follows the advice of its advisory committees, although the agency is not bound by its recommendations. A decision by the FDA is expected next month. If approved, Zelnorm would be the first prescription medication for the treatment of chronic constipation.

The sNDA is supported by data from the two largest randomized, double-blind, placebo-controlled, multi-national Phase III clinical trials ever conducted in the treatment of chronic constipation in more than 2,600 male and female patients. One of the studies included a 13-month extension safety study of nearly 842 patients. Zelnorm was found to significantly increase the frequency of complete spontaneous bowel movements as well as relief of the multiple symptoms patients complain about most -- straining, hard stool, incomplete evacuation and infrequent defecation.

To enroll in the studies, patients had to have CC for at least six months, which was defined as less than three bowel movements per week, accompanied by at least one of the following additional symptoms: straining, incomplete evacuation and/or hard/very hard stools.

“We are pleased the advisory committee has recognized Zelnorm’s ability to address the needs of chronic constipation sufferers,” said Bo Joelsson, M.D., PhD, VP, global head, Gastroenterology Therapeutic Area, Clinical Development of Novartis Pharmaceuticals Corporation. “We look forward to working with the FDA on label discussions to secure approval for Zelnorm for the treatment of CC, so this novel therapy can be made available to patients at the earliest possible opportunity.”

Zelnorm was approved by the FDA in July 2002 as the first and only prescription medication for the short-term treatment of women with irritable bowel syndrome whose primary bowel symptom is constipation.

Zelnorm Clinical Trial Results
The studies demonstrated that Zelnorm-treated patients experienced significantly more complete spontaneous bowel movements (CSBMs) than patients on placebo during 12 weeks. Zelnorm demonstrated early onset of action, with the majority of the Zelnorm-treated patients experiencing a spontaneous bowel movement within the first 24 hours. The response rate for the first four weeks of treatment (primary efficacy variable) was 42 percent in the group receiving 6 mg twice-a-day of Zelnorm -- significantly higher than the 26 percent in the placebo group (p < 0.0001). Over the 12-week period, the response rate for the 6 mg twice-a-day treated group continued to be significantly superior to placebo (44 percent vs. 29 percent).

Significant weekly improvements were observed in Zelnorm-treated patients for stool frequency, consistency and straining compared to placebo. Zelnorm-treated patients also reported less bothersome constipation, abdominal pain/discomfort and bloating/distension. In addition, satisfaction with bowel habits significantly improved with Zelnorm compared to placebo.

In the studies, the incidence of adverse events with Zelnorm was similar to that of placebo. The only adverse event reported more often with Zelnorm 6 mg twice-a-day than placebo was diarrhea (6.6 percent). Diarrhea rarely led to discontinuation of the study (0.9 percent). Typically, diarrhea was transient, lasting two days, and generally resolved without rescue medication or interruption of treatment.

Data from one of the studies, which incorporated a 13-month extension study, showed Zelnorm to be generally safe and well tolerated long term.

About Chronic Constipation
Constipation affects nearly 18 percent of the population, or 37 million people, with more than 4.5 million Americans saying they are constipated most of the time. The condition is evenly distributed across all ages. CC is treated most frequently by primary care physicians, accounts for more than 5.7 million annual visits to emergency rooms and doctors’ offices each year, and leads to more than 282,000 in-patient hospitalizations.

Source: Novartis Pharmaceuticals Corporation 

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