Zelnorm

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Zelnorm(tegaserod maleate)
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• Gastrointestinal Drugs Advisory Committee
  Meeting
• July 14, 2004

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Zelnorm(tegaserod maleate) Introduction
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• John R. Cutt, PhD
• Executive DirectorGlobal Head, Gastrointestinal
  Group
• Drug Regulatory Affairs

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Objectives of Todays Presentation
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• Review Zelnorm phase 3 clinical trial data in
  support of new indication
• Review postmarketing safety data

Zelnorm (tegaserod maleate) is indicated for the
treatment of patients with chronic constipation
and relief of associated symptoms of straining,
hard or lumpy stools, and infrequent defecation
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Zelnorm (tegaserod maleate) Activity in GI Tract

• 5-HT4 receptor partial agonist with affinity for
  5-HT4 receptors in the GI tract
• Pharmacologic activity in GI tract
• Enhances intestinal motility
• Stimulates intestinal secretion
• Inhibits visceral sensitivity
• Demonstrated to improve constipation symptoms in
  IBS-C patients

• Hypothesis Zelnorm offers a unique mechanism of
  action to treat patients suffering from chronic
  constipation

GI Gastrointestinal IBS-C Irritable Bowel
Syndrome with Constipation
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Clinical Development Program for Chronic
Constipation
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• 2 randomized, placebo-controlled pivotal trials
• 12-wk blinded treatment to assess efficacyand
  safety
• 2 mg and 6 mg BID versus placebo
• 2612 patients with chronic constipation
• 1 trial included 13-month extension phase to
  assess long-term safety
• 1 trial included a 4 week withdrawal period

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Zelnorm Experience in Clinical Studies

• July 24, 2002
• FDA approval for the short-term treatment of
  women with irritable bowel syndrome whose primary
  bowel symptom is constipation (6 mg BID)
• Efficacy, safety, and tolerability had been
  documented in 5319 Zelnorm-treated patients in
  clinical trials
• July 14, 2004
• gt 11,600 patients have received Zelnormin
  clinical trials
• 3456 patient-yr exposure

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Worldwide Experience With Zelnorm

• Zelnorm approvals
• 56 countries for patients with irritable bowel
  syndrome with constipation
• 10 countries for patients with chronic
  constipation
• First made available to patients in January 2001
• Over 3 years in clinical practice
• 3 million patients treated globally 2 million
  patients treated in the US

• An estimated 362,000 patient-yr of postmarketing
  experience supports a positive safety profile

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Conclusion
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• Zelnorm 6 mg BID is efficacious and safe for the
  treatment of patients with multiple symptoms of
  chronic constipation
• Clinical data support the proposed
• Zelnorm (tegaserod maleate) is indicated for the
  treatment of patients with chronic constipation
  and relief of associated symptoms of straining,
  hard or lumpy stools, and infrequent defecation

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Agenda and Todays Speakers
Charlene Prather, MD Associate Professor ofInternal MedicineSt. Louis University Chronic Constipation An Unresolved Problem for Many Patients
Eslie Dennis, MD Clinical Development and Medical Affairs, Novartis Zelnorm (tegaserod maleate) Efficacy and Safety in Chronic Constipation
Bo Joelsson, MD, PhD Clinical Research and Development, Novartis ZelnormSafety Overview
Philip Schoenfeld, MD, MSEd, MSc (Epi) Chief, Division of GastroenterologyAnn Arbor VAMCU. of Michigan School of Medicine ZelnormBenefit/Risk Assessment
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Consultants
Felix M. Arellano, MD, FISPE Risk Management Resources, LLCCalifon, NJ
Gary Koch, PhD Department of BiostatisticsUniversity of North Carolina at Chapel Hill
David Lieberman, MD Chief, Division of GastroenterologyOregon Health and Science University
Walter Peterson, MD Department of Internal MedicineUniversity of Texas Southwestern Medical Center