Analgesic Drug Development for Chronic Pain A Brief to DAAODP

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Analgesic Drug Development for Chronic Pain A
Brief to DAAODP AACJuly 29, 2002

• Najib Babul, PharmD
• TheraQuest Biosciences
• nbabul_at_theraquestinc.com

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Conflict of Interest Statement

• Pharmaceutical sponsors with submissions or
  pending submissions before Divisions 550 and 170.
• Views expressed are solely those of TheraQuest
  Biosciences

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Analgesic Drug Development Regulatory Framework

• FDA
• Guideline for the Evaluation of Analgesic Drugs
  (December, 1992)
• EMEA
• Guidance on Clinical Investigation of Medicinal
  Products for Treatment of Pain (CPMP Draft,
  November 2001)

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Supportive Guidelines

• Clinical development programs for drugs, devices
  and biological products intended for the
  treatment of osteoarthritis (FDA Guidance, July
  1999)
• Clinical investigation of medicinal products used
  in the treatment of osteoarthritis (CPMP PTC,
  July 1998)

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Gaps in Regulatory Framework

• Multidose evaluation in acute pain
• Slow-onset drugs with utility in acute pain
• Drugs for neuropathic pain
• Drugs for cancer pain
• Guidance for CLBP, fibromyalgia, myofascial pain
• Chronic pain as an indication

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Potential Models of Chronic Pain

• Myofascial pain
• Low back pain
• Osteoarthritis
• Fibromyalgia
• Mixed-model population
• Neuropathic pain
• Cancer pain

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Response Assessment in Chronic Pain Challenges

• Diverse etiology
• Heterogeneous population within diagnosis
• Referral patterns
• Psychological overlay
• Disability payments and litigation
• Unrealistic outcomes expectations

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It has recently been suggested that replicate
evidence in 3 chronic pain states (models) may be
required for a chronic pain indication .

• What are the potential implications of this?

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Chronic Pain Indication

• Do we have three well established and robust
  models of chronic pain?
• Replicate evidence for a specific sub-indication
  may be appropriate
• Replication in two models of chronic pain OR
  robust and internally consistent evidence in
  single trials in three models may be reasonable
• If burden is too high for a broad indication,
  will we get sub-indications, with attendant
  off-label use?

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Additional Issues

• Use of co-primary endpoints
• - Pain, function, global
• - Some precedence in OA
• - Increased statistical burden?
• - Unrealistic pharmacologic expectation for
  complex disorders?
• Placebo-control vs. active control
• Clinimetric flexibility

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Important Considerations

• DAAODP and DACCADP face somewhat different
  issues
• - Abuse liability, neuropathic pain
• - GI and CV outcomes, inflammatory pain, disease
  modification
• However, harmonized development guidelines may
  help assure cost-effective development, parity
  and timely patient access
• Sponsors with clinical development/submissions
  underway may need special considerations

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Analgesics Drug Development for Chronic Pain A
Brief to DAAODP AACJuly 29, 2002

• Najib Babul, PharmD
• TheraQuest Biosciences
• nbabul_at_theraquestinc.com