OVERVIEW FEBRUARY 15, 2005 Pediatric Advisory Committee

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OVERVIEWFEBRUARY 15, 2005Pediatric Advisory
Committee

• Possible Risk of Cancer from the use of the
  Topical Immunosuppressants Protopic and Elidel
  (tacrolimus and pimecrolimus)
• Dr. Dianne Murphy
• Director, Office of Pediatric Therapeutics, OC,
  FDA

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THE PROBLEM

• Unknown Degree of Serious Risk
• Why Waiting until Risk is More Certain is Not
  Acceptable
• Too many years before we have an answer
• Too many children will have been exposed
• Too late with too little information

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CONCERN LOW

• Animal studies only partially relevant to humans
• High doses used in animal studies
• Absorption levels in humans usually low

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CONCERN HIGH

• Many species, including non-human primates,
  developed cancers
• Biologic Plausibility very high
• Dose effect clearly seen in monkey study
• Documented high systemic levels in some cases
  after topical application
• Children have larger surface area and less
  evolved immune status

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USE HIGH

• Increase use of over 4 fold in 4 years
• Almost 2 Million prescriptions for children
  between June of 2003 and May of 2004
• Approximately half a million for lt 2 y.o.
• Increase in Elidel more marked than Protopic
• For Elidel the majority of use is currently by
  pediatricians

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Pimecrolimus Ointment (Elidel)
From the website http//www.novartis.com/investor
s/en/ir_archive/index.shtml, obtained
02/11/2005 this slide is subject to disclaimers
on the website of origin, and conforms with the
terms of use . FDA cannot vouch for the factual
accuracy of the data presented here.
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Perception of Safety

• In general, Topical products are not usually
  perceived as associated with the same level of
  risk as those that are taken orally or given
  intravenously

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Difficult Message

• HOW DO WE PROVIDE A CLEAR MESSAGE WHEN WE DO NOT
  HAVE A CLEARLY DEFINED RISK?

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BAD OUTCOME5- 10 YEARS FROM NOW

• Applying these creams/ointments to skin does
  contribute to an increase in cancer
• and
• People think they were not provided adequate
  information to assist them in proper use of these
  products.

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Charge to the Committee

• Advise FDA as to your assessment of the Risk
• Define the important Risk messages
• Identify approaches to maximize the successful
  communication of the messages
• Identify how we measure success
• Advise FDA about timelines