Division of Pediatric Drug Development

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Division of Pediatric Drug Development

• Shirley Murphy, MD
• Director, DPDD
• March 3, 2003

DPDD
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Objectives

• Provide an overview of DPDD
• Update on activities
• NICHD/FDA Partnership
• Consultative Activities Across FDA
• New Labels

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Who is in Division of Pediatric Drug Development?

• Medical Officers
• D. Birenbaum L. Grylack
• L. Mathis L. Cooper
• S. Iyasu B. Lindsay
• S. Cummins J. Filie
• S. Buckman
• H. Sachs
• S. Olnes

• Project Managers
• G. Carmouze
• R. Addy
• K. Phucas
• Support Staff
• J. Angel
• P. Curry
• L. Gilmer

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Division of Pediatric Drug Development
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What is the Role of Division of Pediatric Drug
Development?

• Foster pediatric drug development within FDA
• Partner with NICHD to identify and obtain
  pediatric information for off-patent drugs
• Provide consultative service to all centers
  within FDA

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What is the Role of Division of Pediatric Drug
Development?

• Conduct detailed review of proposed pediatric
  trials for on-patent drugs
• Contribute to resolution of scientific/ethical
  issues
• Disseminate new pediatric labeling information

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What is the Role of Division of Pediatric Drug
Development?

• Partnership with NIH/NICHD
• FDA-NICHD Marriage Made In Congress
  

NIH/NICHD
FDA/DPDD
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FDA/NIH Partnership

• Develop List of Drugs for Which Pediatric
  Studies are Needed
• Long, involved iterative process lead by Bill
  Rodriguez/George Giacoia
• Input obtained from Advisory Committee, FDA
  Divisions, NIH Divisions, AAP, USP, and Experts.

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Development of the List

• The BPCA stipulates that in developing and
  prioritizing the list, the NIH shall consider
• the availability of information concerning the
  safe and effective use of the drug in the
  pediatric population
• whether additional information is needed
• whether new pediatric studies concerning the drug
  may produce health benefits in the pediatric
  population

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List Development

• 5/19/00 FDA publishes list of 426 drugs where
  further pediatric studies are needed
• 6/11/02 Pediatric Advisory Subcommittee
  Meeting
• 7/02 NIH gives list of 426 drugs to USP
• USP removes some on-patent drugs
• 7/15/02 NIH sends new list of 284 drugs to
  FDA
• FDA reviews list - removes on-patent drugs,
  biologics, 505b approvals, off-market drugs,
  duplicates groups drugs by division/disease

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List Development

• 9/18/02 FDA sends refined list of 180 drugs
  back to NIH
• NIH ranks 180 drugs with input from NIH
  institutes, AAP and experts
• NIH divides drug list
• Lower Priority High Priority
• (List kept at NIH)

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List Development

• 10/21/02 NIH sends 34 Drug High Priority List
  back to FDA
• FDA review divisions rank drugs on public
  health benefit, other approved products in
  class, other options adds inpatient/outpatient
  data
• 11/27/02 FDA sends 34 Drug List with above
  information to NIH
• NIH obtains written review by
  subspecialty expert on each drug

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List Development

• 12/10/02 NIH convenes expert panel (AAP, COD,
  pharmacologists, subspecialty pediatricians,
  FDA, USP) each drug is reviewed scored by
  NIH system (100 high-500 low)
• Scores totaled by NIH
• 12/13/02 FDA/NIH meet select 12 drugs from
  top 16
• 1/21/03 NIH publishes List of Drugs for
  Which Pediatric Studies are Needed

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2003 List of Drugs for Which Pediatric Studies
Are Needed

• Azithromycin
• Baclofen
• Bumetanide
• Dobutamine
• Dopamine
• Furosemide

• Heparin
• Lithium
• Lorazepam
• Nitroprusside
• Rifampin
• Spironolactone

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FDA/NIH Off-Patent Drug Process

• BPCA establishes a process to study off-patent
  drugs in collaboration with NIH
• DPDD performs existing literature/label review
• DPDD writes detailed plan for studies (Written
  Request)
• No response to WR, NICHD issues Request for
  Contract (RFC)

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Process for the Study of Off-Patent Drugs
Priority List of Off-Patent Drugs
Industry agrees to conduct studies
FDA issues Written Request
yes
Industry declines to conduct studies
no
Industry has 30 days to respond
Referral to NIH
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FDA/NIH Partnership

• RFC for Coordinating Center Published in Federal
  Business Opportunities
• RFCs to be published
• Nitroprusside - to reduce blood pressure in
  pediatric patients
• Lorazepam - long-term, continuous sedation in ICU
  setting
• Lorazepam - treatment of status epilepticus
• 5 other off-patent drugs in process

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FDA/NIH Partnership

• NICHD/FDA Newborn Drug Development Initiative
• BPCA recognizes neonates as a specific pediatric
  subpopulation
• Goal foster the development of safe and
  effective drug therapies for the pre-term and
  neonatal population

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FDA/NIH Partnership

• NICHD/FDA to conduct workshop in early 2004 to
  frame the state of the art and define research
  priorities for pain control, cardiac,
  neurological, and pulmonary diseases
• Planning meeting with 50 multidisciplinary
  experts held 2/10/03
• Working groups established

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Consultative Service To All Centers Within FDA

• Devices
• Cochlear Implants
• Breast Implants
• GI Devices
• Other
• CFSAN
• Infant formula additives
• Other
• phthalates
• scientific/safety/ ethical issues
• Formal Consulting Process with Counter-Terrorism

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Prussian Blue Label

• Treatment of internal contamination of
  radioactive and non-radioactive Cesium or
  Thallium
• Efficacy extrapolated from adult data, safety and
  efficacy supported by information from pediatric
  patients exposed in the Goiânia accident
• 27 pediatric patients received PB after exposure
  to Cesium
• Reduced half life by 46 in adolescents and 43
  in children

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Labeled Products(6/02 - 2/03)

• Isotretinoin
• Famotidine
• Omeprazole
• Mometasone
• Montelukast
• Tamoxifen
• Lamivudine
• Atorvastatin

• Simvastatin
• Cetirizine
• Pravastatin
• Vinorelbine
• Atomoxetine
• Fluoxetine
• Busulfan

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Labeled Products with Significant New Information

• Montelukast (Singulair) - prophylaxis and chronic
  treatment of asthma
• dose, PK AE profile in pts. 12-23 mo.
  2-5yrs.
• new formulations 4mg chewable tablet 4mg oral
  
• granule

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Labeled Products with Significant New Information

• Mometasone (Elocon) - Corticosteroid responsive
  dermatoses
• Cream Ointment
• evidence of HPA Axis suppression in ped patients
  6-23mo.
• skin atrophy in pediatric patients 6mo-2yr.
• Should not be used for treatment of diaper
  dermatitis
• Lotion
• Safety and effectiveness have not been
  established in ped
• patients below 12 yrs and use is not
  recommended
• Should not be used for treatment of diaper
  dermatitis

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Labeled Products with Significant New Information

• Tamoxifen (Nolvadex)
• safety and effectiveness studied in female
  patients aged 2-10 yrs. with McCune-Albright
  Syndrome and precocious puberty treated for up to
  12 months. Long term effects have not been
  established.
• relative to prestudy baseline
• 50 reduction in frequency of vaginal bleeding
• Reduction in mean rate of increase of bone age
• linear growth rate reduced in majority of
  patients during treatment
• mean uterine volume increased after 6 months of
  therapy and doubled at end of 1 yr. study

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Labeled Products with Significant New Information

• Pravastatin (Pravachol) - Heterozygous Familial
  Hypercholesterolemia
• new indication in boys and girls 8-18yrs
• Atorvastatin (Lipitor) - Heterozygous Familial
  Hypercholesterolemia
• new indication adolescent boys and girls
  (post-menarche)
• Simvastatin (Zocor) - Heterozygous Familial
  Hypercholesterolemia
• new indication in adolescent boys and girls (at
  least one year post menarche) 10-17yrs.

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Labeled Products with Significant New Information

• Vinorelbine (Navelbine)
• no meaningful clinical activity in a variety of
  tumors (e.g., recurrent solid malignant tumors,
  including rhabdomyosarcoma/undiff sarcoma,
  neuroblastoma, and CNS tumors)
• Atomoxetine (Strattera) - ADHD down to 6yrs.
• First non-stimulant (SNRI) drug labeled for ADHD
• NME/non-scheduled drug
• unknown whether final adult height or weight is
  affected by treatment
• patients on long-term treatment should be
  monitored

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Labeled Products with Significant New Information

• Fluoxetine (Prozac) - Major Depressive Disorder
  (MDD)
• Obsessive Compulsive Disorder
  (OCD)
• Effectiveness established MDD 8-17yrs. OCD
  7-17yrs.
• Decreased weight gain observed with use of
  fluoxetine as with other SSRIs
• In one 19 week clinical trial ped subjects
  treated with fluoxetine gained an average of
  1.1cm less in height (p0.04) and 1.1kg less in
  weight (p0.008) than those treated with placebo
• height and weight should be monitored
  periodically in pediatric patients treated with
  fluoxetine

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Labeled Products with Significant New Information

• Fluoxetine (Prozac) - MDD OCD (cont.)
• Mania/hypomania led to discontinuation of 1.8 of
  fluoxetine treated patients vs 0 of placebo
  controlled patients in 3 placebo controlled
  trials combined
• regular monitoring for the occurrence of
  mania/hypomania is recommended

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Summary

• The FDA is the most interesting and fun place
  you could ever work
• Jane Henney,
  MD 5/02
• (Former FDA Commissioner)
• Please send me the CVs of all your friends
• and colleagues.

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To Learn More

• Internet
• www.fda.gov/cder/pediatrics
• Peds Line
• 301-594-PEDS
• Email
• pdit_at_cder.fda.gov