Psychopharmacologic Drugs Advisory Committee

1
C

• Psychopharmacologic Drugs Advisory Committee
• November 4, 2002

2
Clozaril (clozapine)Introduction and Regulatory
Overview
C

• Roy W. Dodsworth
• Executive DirectorDrug Regulatory Affairs
• Novartis Pharmaceuticals Corporation

3
Overview
C

• Clozaril is an antipsychotic agent belonging to
  the dibenzodiazepine class of drugs
• Considered first atypical antipsychotic agent
• First approved in Austria 1969
• Original New Drug Application (NDA 19-758)
• Approved September 26, 1989
• Approved in gt 150 countries
• Supplemental New Drug Application (sNDA
  19-758/S-047)
• Filed March 1, 2002
• Submitted in Canada and Australia
• Planned submissions worldwide (eg, EU)

4
C
Clozaril Indication(s)

• Current
• Clozaril is indicated for the management of
  severely ill schizophrenic patients who fail to
  respond adequately to standard drug treatment for
  schizophrenia.

Proposed Additional Clozaril is indicated for
reducing the risk of emergent suicidal behavior
in patients with schizophrenia or schizoaffective
disorder who are judged to be at risk for
emergent suicidal behavior, based on history and
recent clinical state. Suicidal behavior refers
to actions by a patient that put him/herself at
high risk for death.
5
Study Supporting New Indication
C
International Suicide Prevention Trial
(InterSePT) A prospective, randomized,
international, parallel-group comparison of
Clozaril/Leponex versus Zyprexa in the
reduction of suicidality in patients with
schizophrenia or schizoaffective disorder who are
at risk for suicide
6
Key Interactions With the FDA (1)
C

• Date Action
• Mar 31, 1993 FDA requests assessment of
  mortality
• May 31, 1995 Novartis submits Mortality of
  People Using Clozapine report
• Aug 15, 1995 Novartis submits supplemental applic
  ation for reduction of suicidal behavior
• Feb 23, 1996 FDA issues not approvable letter

7
Key Interactions With the FDA (2)
C

• Date Action
• Jan 16, 1998 Novartis submits InterSePT protocol
• Mar 1, 2002 Novartis submits NDA 19-758/S-047
• Aug 30, 2002 FDA issues approvable letter
• Nov 4, 2002 Advisory Committee Meeting

8
Objectives of Novartis Presentations
C

• To demonstrate that suicidal behavior in patients
  with schizophrenia and schizoaffective disorder
  represents a new indication
• To demonstrate that the results from the
  InterSePT study, together with those from other
  published studies, support the efficacy of
  Clozaril in the treatment of suicidal behavior
  in this patient population

9
Agenda
C

• Introduction . . . . . . . . . . . . . . . . . .
  . . . . .Roy W. Dodsworth
• Overview of Suicidal Behavior. . . . Herbert Y.
  Meltzer, MD
• InterSePT Study Results . . . . . . . . . .
  . Rocco Zaninelli, MD
• Suicide Monitoring Board . . . . . K. Ranga Rama
  Krishnan,
  MB, ChB
• Benefit/Risk . . . . . . . . . . . . . . . . . .
  . . . . . John M. Kane, MD
• Question and Answer Moderator. . . . Rocco
  Zaninelli, MD