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Approval Recommended for Use of Zelnorm in Chronic Constipation by FDA Advisory Committee
ROCKVILLE, Md., July 14 /PRNewswire-FirstCall/ -- Novartis Pharmaceuticals Corporation announced today 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, MD, 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
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.
Zelnorm is indicated for the short-term treatment of women with IBS whose primary bowel symptom is constipation. The safety and effectiveness of Zelnorm in men with IBS with constipation have not been established.
Zelnorm is the first agent proven to provide women with relief of the abdominal discomfort or pain, bloating and constipation of IBS, and it is the first in a novel class of drugs. Zelnorm acts as an agonist at 5HT(4) (serotonin type 4) receptors in the GI tract. Zelnorm mimics the natural effects of serotonin by activating 5HT(4) receptors, which normalizes impaired motility in the GI tract, inhibits visceral sensitivity and stimulates intestinal secretion.
In IBS with constipation clinical trials, tolerability to Zelnorm was similar to placebo. The only adverse event reported notably more often with Zelnorm than with placebo was diarrhea (nine vs. four percent). The majority of patients reporting diarrhea had a single episode and in most cases, diarrhea occurred in the first week of treatment. Typically, it resolved with continued therapy. Serious consequences of diarrhea, including hypovolemia, hypotension and syncope, have been reported in the clinical studies (0.04 percent) and during marketed use of Zelnorm. In some cases, these complications have required hospitalization for rehydration. Overall, safety data is now available in more than 11,600 patients who have enrolled in clinical trials assessing Zelnorm's safety and efficacy in various GI conditions.
Zelnorm was developed by Novartis and is also known in some countries as Zelmac. It is approved in more than 55 countries for IBS with constipation. Approximately three million patients worldwide have been treated with Zelnorm for IBS with constipation. Zelnorm also is approved for use in chronic constipation in 10 countries, including Mexico and Latin America. Zelnorm is being studied as a potential treatment for other important GI disorders, including gastroesophageal reflux disease (GERD) and dyspepsia.
This release contains certain forward-looking statements relating to the Company's business, which can be identified by the use of forward-looking terminology such as "if approved," "might benefit," "would be," "look forward," or similar expressions, or by express or implied discussions regarding the potential approval of Zelnorm for any chronic constipation or for any other new indications, or regarding potential future sales of Zelnorm. Such forward-looking statements reflect the current views of the Company with respect to future events and are subject to certain risks, uncertainties and assumptions. There can be no guarantee that Zelnorm will be approved for chronic constipation or for any other new indications by the FDA or in any other country. Nor can there be any guarantee regarding potential future revenues from Zelnorm. In particular, management's expectations could be affected, among other things, uncertainties relating to unexpected regulatory actions or delays, government regulation generally, new clinical data, unexpected clinical trial results, the ability to obtain or maintain patent or other proprietary intellectual property protection, competition in general, government pricing pressures, and other risks and factors referred to in the Company's current Form 20-F on file with the Securities and Exchange Commission of the United States. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
Novartis Pharmaceuticals Corporation researches, develops, manufacturers and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including central nervous system disorders, organ transplantation, cardiovascular diseases, dermatological diseases, respiratory disorders, cancer and arthritis. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG , a world leader in pharmaceuticals and consumer health. In 2003, the Novartis Group's businesses achieved sales of USD 24.9 billion and a net income of USD 5.0 billion. The Group invested approximately USD 3.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 78,500 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com/.
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