Table of Contents
PPT Slide
Agenda
Experts Available for the Committee
Chemical Structure
Regulatory Overview
Recognition of Abuse
Proposed Indication
Prevalence of Narcolepsy in the U.S.
Narcolepsy - Medical Need
Narcolepsy - Cataplexy
Narcolepsy - A Disabling Disorder
Driving Effects and Accidents
Objective Measurement of EDS
Abnormal Regulation of REM Sleep
PPT Slide
Partial Efficacy of Treatments: MWT
Hypocretin Deficiency in Narcolepsy
Need for New Treatments
William Houghton, M.D. Chief Operating Officer & Medical Officer, Orphan Medical, Inc.
PPT Slide
OMC-GHB-2 Study
OMC-GHB-2 Efficacy Parameters
OMC-GHB-2 Inclusion Criteria
OMC-GHB-2 Overall Study Design
Cataplexy Attacks per Week
OMC-GHB-2 Primary Efficacy Total Cataplexy
OMC-GHB-2 Primary Efficacy Cataplexy (Median Percent Change)
Secondary Efficacy Epworth Sleepiness Scale
OMC-GHB-2 Secondary Efficacy Daytime Sleepiness (medians)
OMC-GHB-2 Other Daytime Sleepiness Parameters
Clinical Global Impression (CGI)
Clinical Global Impression of Change at Endpoint OMC-GHB-2 – By Dose Group
Post-Hoc Responder/Non-Responder Analysis
OMC-GHB-2 Secondary Efficacy CGIc
OMC-GHB-2 Other Variables
OMC-SXB-21
OMC-SXB-21 Objective
OMC-SXB-21 Study Design
OMC-SXB-21 Cataplexy Median Change from Baseline
OMC-SXB-21 Cataplexy Median Change from Baseline
PPT Slide
Scrima Cross-over Trial Study Design
Scrima Trial Number of Cataplexy Attacks / Week
Lammers Trial Study Design
Lammers Trial Cataplexy
Lammers Trial Other Measures
OMC-GHB-3
OMC-GHB-3 Cataplexy – Median Percent Change
OMC-GHB-3 Mean ESS for All Dose Groups
OMC-GHB-3 Dose Distribution – 6 & 12 Months
OMC-SXB-21 Supports Efficacy in OMC-GHB-3 Cataplexy Attacks / Week: OMC-GHB-2/3 Patients in OMC-SXB-21
Summary of Efficacy
William Houghton, M.D. Chief Operating Officer & Medical Officer, Orphan Medical, Inc.
Xyrem Pharmacokinetic Studies
Plasma Concentrations of Oxybate (GHB) After 4.5 Grams (2x2.25) or 9.0 Grams (2x4.5) of Xyrem to Normal Volunteers (Mean, Standard Error)
Plasma Oxybate (GHB) Concentration After an Oral Dose of 4.5 Grams of Xyrem to Normal Volunteers Following a High Fat Meal or after an Overnight Fast
PPT Slide
Xyrem Pharmacokinetics: Summary
Xyrem Pharmacokinetics: Summary
Polysomnographic Effects of Xyrem
Effects of Sodium Oxybate on Quantitative EEG Parameters in Narcoleptics
Scrima and LammersTrials Nocturnal PSG Data
OMC-SXB-20 Study Design
OMC-SXB-20 Study Results
Change in Slow Wave (Stages 3&4) Sleep Duration
Total Slow Wave (Stages 3&4) Sleep Duration
Delta Power
MWT Sleep Latency (Daytime)
Epworth Sleepiness Score (Daytime)
Correlation Between Daytime and Nocturnal Effects
OMC-SXB-20 Overall Conclusions
William Houghton, M.D. Chief Operating Officer & Medical Officer, Orphan Medical, Inc.
PPT Slide
Sodium Oxybate Exposure All Trials Including Scharf
Sodium Oxybate Exposure Updated ISS Excluding Scharf
Updated ISS Database Summary of Patient Exposure by Dose
Updated ISS Database Treated Patient Disposition
Updated ISS Database Summary of Adverse Events
Updated ISS Database Dose Distribution of Adverse Events
Updated ISS Database Most Frequent Adverse Events (n=399)
Placebo-Controlled Clinical Trials Most Frequent Adverse Events
OMC-SXB-21 Safety Summary
OMC-SXB-21 Possible Withdrawal Associated AEs
Scharf Trial
Adverse Events
Scharf Trial (16 years) Patient Disposition
Scharf Trial (16 years) AE Incidence
Comparison of Updated ISS Database to Scharf Trial (First 6 months) Most Frequent Adverse Event Incidence
Adverse Events of Special Interest
Incontinence
Incontinence
Incontinence Method
Urinary Incontinence
Fecal Incontinence
Incontinence Conclusion
Convulsions
“Confusion”
Summary of Adverse Events COSTART Coded as “Confusion”
Updated ISS Verbatim Terms for “Confusion”
Updated ISS Action Taken for AE of Confusion
Controlled Trial: OMC-GHB-2 Confusion as AE
Confusion -- Conclusions
Neuropsychiatric Events
Summary of Neuropsychiatric Adverse Events
Updated ISS Summary of Neuropsychiatric Events
Scharf Open-Label Trial Summary of Neuropsychiatric Events
Conclusions Neuropsychiatry and Confusion
Sleep Disorders Sleepwalking (Somnambulism)
Sleepwalking Summary of Events
Sleepwalking Differential Diagnoses
Sleepwalking in Controlled Trials
Sleepwalking -- Conclusions
Summary of Safety
Summary of Safety
Safety Conclusion
William Houghton, M.D. Chief Operating Officer & Medical Officer, Orphan Medical, Inc.
Benefit-Risk Assessment Proposed Indication
Narcolepsy - Overview
Benefits of Xyrem
Clinical Benefits of Xyrem
Safety of Xyrem
Somnambulism
Enuresis
Laboratory Measures
Tolerance
Withdrawal Phenomenon
Abuse Issues
Conclusions
Robert Balster, Ph.D. Medical College of Virginia
Abuse Liability of Xyrem
GHB and GHB-like Substances
Abuse of GHB-like Substances Results Primarily From Availability
PPT Slide
Scientific Data on the Abuse Potential of GHB
Conclusions From Abuse Potential Studies
Potential Sources of Abuse of Xyrem
Abuse Among Patients is Unlikely
Illicit Diversion of Xyrem Unlikely
GHB, GBL and 1,4- Butanediol Comparison of Production Quantities
Abuse Liability Summary
Patti Engel, R.N., BSN Vice President of Marketing & Sales, Orphan Medical, Inc.
Xyrem Success Program
Xyrem Success Program
Risk Management Through Risk Confrontation
Standard Pharmaceutical Distribution
Xyrem Closed Distribution System
Xyrem’s Distribution
Physician Promotion and Education
Physician Promotion and Education
Physician Success Program Materials
Prescription Process
Physician Verification
Patient Verification
Pre-Shipment Patient Counseling
Rapid Trac® System
Patient Success Program Materials
Post-receipt Contact
Benefits of Central Data Repository
Xyrem Success Program
Xyrem Closed Distribution System
PPT Slide
Xyrem® (Sodium Oxybate) oral solution
OMC-SXB-21 Median Change In Cataplexy Attacks by Dose
Updated ISS Database Summary of Patient Exposure by Dose
Updated ISS Database with Scharf Summary of Patient Exposure by Dose
Updated Integrated Summary of Safety Summary of “Confusion” Events
PPT Slide
|