Psychopharmacologic Drugs Advisory Committee

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• Psychopharmacologic Drugs Advisory Committee
• June 16, 2003

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Introduction and Regulatory Overview

• James Rawls, Pharm.D.
• Associate DirectorDrug Regulatory Affairs
• Novartis Pharmaceuticals Corporation

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Clozaril - Pharmacology

• Pharmacologically considered a dibenzodiazepine
  that binds to dopamine receptors
• Paucity of extrapyramidal side effects (EPS)
• First atypical antipsychotic available in the
  United States

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Clozaril - Indications

• First approved in 1969 for treatment of
  schizophrenia
• First approved in the United States in 1989 for
  the management of treatment-resistant
  schizophrenia
• Approved in 2002 for treatment of recurrent
  suicidal behavior in patients with schizophrenia
  and schizoaffective disorder

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Regulatory Overview (1)

• 1989
• Clozaril was launched in the US
  (treatment-resistant patients) with weekly White
  Blood Cell (WBC) count monitoring
• 1998
• Following 1997 Advisory Committee Meeting a
  revised monitoring system was implemented (weekly
  for 6 months then biweekly thereafter)
• Monitoring frequency should be reduced after six
  months to every two weeks
• After implementation of the current monitoring
  system, evaluate the impact this system had on
  the rate of agranulocytosis
• First generic version of Clozaril is available

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Regulatory Overview (2)

• 2001
• FDA requested update regarding safety of current
  monitoring frequency
• 2002
• Submitted data regarding current monitoring
  frequency
• New indication approved for recurrent suicidal
  behavior
• 2003
• Second FDA AC Meeting regarding monitoring
  frequency

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Objective of Novartis Presentations

• To present data that will facilitate the
• discussion regarding the various
• questions posed to the committee

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Agenda

• Introduction . . . . . . . . . . . . . . . . . .
  . . . .James Rawls, PharmD
• Overview of Agranulocytosis . . . . . . . . . .
  Stanton Gerson, MD
• Clozaril Registry Data . . . . . . . . . . . .
  . . . . Vinod Kumar, MD
• Quantitative Analysis of US Data . . Lawrence
  Hauptman, PhD
• Summary and Conclusion . . . . . . . . . . . . .
  . . . John Kane, MD