Efficacy of Testosterone Transdermal System (TTS) for Treatment of HSDD in Surgically Menopausal Women on Concomitant Estrogen Daniel Davis, MD, MPH Division of Reproductive and Urologic Drug Products December 2, 2004

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Efficacy of Testosterone Transdermal System (TTS)
for Treatment of HSDD in Surgically Menopausal
Women on Concomitant EstrogenDaniel Davis, MD,
MPHDivision of Reproductive and Urologic Drug
ProductsDecember 2, 2004
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Clinical Efficacy Issues

• First application for this indication
• Clinical significance of small treatment effects
• Small ? in satisfactory sexual events (SSEs)
• Small changes in secondary endpoints
• Strong placebo effect relative to TTS effect
• Methodology for determining a clinically
  meaningful treatment effect

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Clinical Development Program

• FDA Draft Guidance and advice followed
• 3 Instruments developed to assess efficacy
• Two placebo-controlled Phase 3 trials that
  evaluated efficacy over 6 months
• Study to determine the magnitude of change that
  is clinically meaningful

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Key Inclusion-Exclusion Criteria

• Surgically menopausal, on stable estrogen
• Acquired HSDD diagnosed by answer to5 questions
• Generally good health, without history of
  diabetes, cardiovascular disease
• No specific entry testosterone level
• Stable partner relationship

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Diagnosis of Acquired HSDD

• Was your sex life satisfying before the surgery?
• Have you had a meaningful decrease in sexual
  desire since surgery?
• Have you had a significant ? in sexual activity?
• Are you distressed by the changes?
• Would you like to see an ? in desire for sex and
  sexual activity?

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Primary and Secondary Endpoints

• Primary endpoint
• Change from baseline in satisfactory sexual
  events (SSEs) per 4 weeks
• Secondary endpoints
• Change in personal distress score on the Personal
  Distress Scale
• Change in sexual desire domain in the Profile of
  Female Sexual Function

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Satisfactory Sexual Events(Mean Change from
Baseline per 4 Weeks)
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Personal Distress Score(Mean Change from
Baseline)
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Sexual Desire Score(Mean Change from Baseline)
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Summary of Efficacy Findings(Change from
Baseline)
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TTS Treatment Effects Compared to Normal Values
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Determination of Minimal Meaningful Treatment
Effects

• Blinded exit interview of subset (n 132)
• Considering everything that we have talked
  about today, would you say that you experienced
  a meaningful benefit from the study patches?
• On TTS 52 yes On Placebo 31 yes
• Analysis Receiver Operating Characteristic (ROC)
• Results
• SSE 1.1 event per 4 weeks
• Desire 8.9 change in score
• Distress decrease of 20 or more in score

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SSEs - Percent Responders (Phase 3 Studies
Combined)
Differences in percent of responders (TTS minus
placebo) ranged from 12 to 14
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Clinical Efficacy Summary

• Small, statistically significant increase in
  mean number of SSEs
• TTS - Placebo 1 event per 4 weeks
• Small changes in secondary endpoints
• Distress Score
• TTS - Placebo - 6.7 units
• Desire Score
• TTS - Placebo 5.1 units
• Small increase in SSEs responders
• TTS -Placebo 14 (gt1 event/4 wks)