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New Data for Tegaserod maleate Demonstrate Relief of Multiple Symptoms of Dysmotility-Type Dyspepsia

Results presented at the American College of Gastroenterology Annual Scientific Meeting offer hope for patients living with this digestive condition

LAS VEGAS, NV -- October 24, 2006 -- Zelnorm (tegaserod maleate) has demonstrated potential to treat the multiple symptoms of dysmotility-type dyspepsia, according to new data being presented today at the American College of Gastroenterology (ACG) Annual Scientific Meeting in Las Vegas.

Dysmotility-type dyspepsia is a common digestive condition characterized by discomfort and bloating that occurs in the abdominal area. Dysmotility-type dyspepsia is a subgroup of functional dyspepsia, a condition that affects an estimated 25 percent of the adult population, or more than 52 million Americans, and costs an average of $2.5 billion annually in direct and indirect healthcare costs. There are no prescription medications approved to treat dysmotility-type dyspepsia or the symptoms associated with the condition.

"These multiple symptoms have a very significant impact on patients' lives," said Loren Laine, MD Professor of Medicine, University of Southern California School of Medicine. "For patients with moderate to severe symptoms the results of these studies are promising and suggest a benefit for tegaserod."

Pooled data from two pivotal studies (n = 2,667) show a positive benefit of Zelnorm treatment versus placebo for women with dysmotility-type dyspepsia symptoms, including early satiety (extreme sensation of fullness soon after starting a normal sized meal that makes it difficult to finish the meal), post-prandial fullness (uncomfortable feeling of fullness after a meal) and bloating. The data showed statistically significant treatment benefit of Zelnorm (P <.05) for the primary endpoints -- percent of days with satisfactory relief of dyspepsia symptoms and improvement in composite average daily symptom score.

In patients with more severe baseline dyspepsia symptoms, Zelnorm showed a greater treatment effect versus placebo. Although Zelnorm improves dysmotility and reduces visceral hypersensitivity in the lower gastrointestinal tract, further research is needed to assess the mechanism of action of Zelnorm in potentially relieving post-prandial fullness, early satiety and bloating associated with dysmotility-type dyspepsia.

"We know that Zelnorm uniquely treats a major underlying cause of dysmotility in the lower GI tract and these new data for the first time suggest the possibility of treating conditions of the upper GI tract," commented James Shannon, MD, Global Head of Development at Novartis Pharma AG. "Millions of patients currently rely on Zelnorm to relieve IBS with Constipation and Chronic Constipation and these new study results may offer hope of relief for those living with symptoms of dysmotility-type dyspepsia."

About the Studies
A total of 2,667 women, at least 18 years of age, were randomized in the two studies. Study participants were enrolled in accordance with ROME criteria for dysmotility-type dyspepsia. The co-primary endpoints for each study were the percentage of days with satisfactory relief of dyspepsia symptoms and the composite average daily symptom score (CADSS). The symptom score endpoints were measured using a 7-point Likert scale ("1 = no discomfort at all" to "7 = very severe discomfort"). Patients were excluded from these studies if they had concomitant heartburn, IBS or GERD. All patients included had to have at least mild dyspepsia.

Study 1 showed a statistically significant improvement with Zelnorm treatment for the endpoints of percentage of days with satisfactory relief (tegaserod 32.24% vs. placebo 26.63%) and composite average daily symptom score (tegaserod 3.14 vs. placebo 3.35) compared to placebo (p=0.0002, p<0.0001 respectively). Study 2 showed a trend in favor of Zelnorm as compared with placebo for both endpoints, percentage of days with satisfactory relief (tegaserod 31.87% vs. placebo 29.36%) and composite average daily symptom score (tegaserod 3.15 vs. placebo 3.23) compared to placebo, but statistical significance was not achieved (p=0.0662, p=0.0936). In both studies, tegaserod showed greater benefit over placebo. Pooled data demonstrated a statistically significant benefit of tegaserod over placebo for both primary endpoints.

The adverse event profiles in both studies were consistent with the established safety and tolerability profile of Zelnorm. The most common adverse event was diarrhea, which occurred in about 19% of Zelnorm-treated patients as compared with 4-5% of placebo patients. In Zelnorm-treated patients experiencing moderate to severe symptoms, the rate of diarrhea was 13.6% as compared with 3% of placebo treated patients. These events tended to occur in the first week of therapy, were transient, self-limiting and usually did not require discontinuation. (Discontinuation rate for diarrhea was 3-5% for Zelnorm. Discontinuation due to diarrhea was 0.1-0.5% for placebo.) There were no serious consequences of diarrhea reported in the pivotal studies.

About Dysmotility-Type Dyspepsia
Dysmotility-type dyspepsia is a common digestive condition characterized by discomfort that occurs in the abdominal area. Discomfort is defined by symptoms of early satiety (extreme sensation of fullness soon after the start of a normal sized meal that makes it difficult to finish the meal), abnormal postprandial fullness (uncomfortable feeling of fullness after a meal), bloating, nausea and vomiting. The symptoms of dysmotility-type dyspepsia can be chronic and disruptive. These patients often suffer from other gastrointestinal disorders such as Irritable Bowel Syndrome, Chronic Constipation and GERD.

About Zelnorm
Zelnorm is the first in a novel class of drugs that act as an agonist at 5HT4 (serotonin type 4) receptors. Zelnorm mimics the natural effects of serotonin by activating 5HT4 receptors, which normalizes impaired motility in the GI tract, inhibits visceral sensitivity and stimulates intestinal secretion. Overall, safety data is now available in more than 16,000 patients who have enrolled in clinical trials assessing Zelnorm's safety and efficacy in various GI conditions.

Zelnorm is indicated for the treatment of men and women less than 65 years of age with Chronic Idiopathic Constipation. The effectiveness of Zelnorm in patients 65 years or older with Chronic Idiopathic Constipation has not been established. Zelnorm is also indicated for the short-term treatment of women with IBS whose primary symptom is Constipation. The safety and effectiveness of Zelnorm in men with IBS with Constipation have not been established. Efficacy beyond 12 weeks has not been studied.

Serious consequences of diarrhea, including hypovolemia, hypotension, and syncope, have been reported with Zelnorm. Zelnorm should be discontinued immediately in patients who develop severe diarrhea, hypotension, or syncope. Zelnorm should not be initiated in patients who are currently experiencing or frequently experience diarrhea.

Zelnorm should be discontinued immediately in patients with new or sudden worsening of abdominal pain. Ischemic colitis and other forms of intestinal ischemia have been reported in patients receiving Zelnorm during marketed use of the drug. In some cases, hospitalization was required. Patients who develop symptoms of ischemic colitis such as rectal bleeding, bloody diarrhea, or new or worsening abdominal pain should discontinue therapy immediately and be evaluated. Zelnorm should not be resumed if ischemic colitis or other forms of intestinal ischemia are diagnosed. A causal relationship between Zelnorm and these events has not been established. The only adverse events reported significantly more often with Zelnorm than with placebo were diarrhea (7% vs. 3%) in Chronic Constipation studies, and headache (15% vs. 12%) and diarrhea (9% vs. 4%) in IBS with Constipation studies.

Zelnorm, discovered and developed by Novartis, is approved for the treatment of IBS-C in more than 55 countries including Australia, Switzerland, Canada, the United States, Mexico, China and Brazil. Zelnorm is also approved for the treatment of Chronic Constipation in more than 20 countries including the United States, Canada and Mexico. Novartis markets Zelnorm (tegaserod maleate) in the US, Canada, Philippines and South Africa; and under the trademark Zelmac (tegaserod) in Switzerland, Latin America and Asia-Pacific regions.


SOURCE: Novartis AG

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