Palifermin (Kepivance

1
Palifermin (Kepivance)

• Recombinant Human Keratinocyte Growth Factor
• Oncologic Drugs Advisory Committee
• Pediatric Subcommittee
• October 20, 2005
• Amgen Inc.

2
Palifermin Pediatric Development

• Pre-registration Phase

Sept 2000 End of Phase 2
Sept 03 Pre- BLA
Jun 04 Adult BLA submission
Adult studies conducted
2000
2001
2002
2003
2004
Pediatric PMC agreed
Pediatric Phase 1/2 design
Early Discussions
BLA Biologics License Application PMC
Post-Marketing Commitment
3
Palifermin Pediatric Program Former Proposal

• Phase 1/2 Study with COG
• Patients B-NHL receiving COP/COPADM/CYM
• Age 3-16 years
• Palifermin i.v. 3 consecutive days before
  chemotherapy

Phase 1
Phase 2

• Palifermin vs. Placebo
• Safety
• Efficacy

• Dose escalation,
• 4 dose cohorts
• Safety, Pharmacokinetics

COG Childrens Oncology Group. B-NHL B-cell
Non-Hodgkins Lymphoma, stage 1-2 COP/COPADM/CYM
multi-agent chemotherapy regimen
4
Palifermin Pediatric Development

• Post-registration Phase

Dec 04 Adult BLA approved
Mar 05
Jun 05
Sept 05
2004
2005
Pediatric PMC
Change in Standard Therapy
Revised Study Proposal
Further Study Specification
5
Palifermin Pediatric Program Current Proposal

• Separate Studies with PBMTC and COG
• Patients Acute leukemias, neuroblastoma
• Age 1-16 years, 3 age groups
• Palifermin i.v. 3 consecutive days before after
  chemo

Phase 1
Phase 2

• Dose escalation, 4 dose cohorts
• Safety
• Pharmacokinetics

• Safety
• Homogeneous
• population
• Age 1-6 years

• Efficacy, Safety
• Randomized
• Broad population
• Age 1-16 years

PBMTC Pediatric Blood and Marrow Transplant
Consortium COG Childrens Oncology Group
6
Palifermin Pediatric ProgramPhase 1 with PBMTC
Sites

• Objectives Dose finding, safety,
  pharmacokinetics
• Patients ALL or AML requiring TBI and high-dose
  chemotherapy with alloHSCT
• 36-72 patients
• 3 age groups (1-2, 3-11 and 12-16 years)
• Conventional dose escalation
• 4 dose cohorts (20 40 60 80 ?g/kg/d) given
  3 consecutive days before and after chemotherapy
• Dose escalation decisions for each age group

PBMTC Pediatric Blood and Marrow Transplant
Consortium. ALL Acute Lymphoblastic Leukemia,
AML Acute Myeloid Leukemia, TBI Total Body
Irradiation, alloHSCT allogeneic hematopoietic
stem cell transplant.
7
Palifermin Pediatric ProgramProposed Phase 2
with COG Safety

• Objective Safety
• Patients Homogeneous patient population
• 60-80 patients, randomized
• Age group lt 6 years
• Autologous transplant setting
• Neuroblastoma
• Doses established in Phase 1

COG Childrens Oncology Group
8
Palifermin Pediatric ProgramProposed Phase 2
with COG Efficacy

• Objectives Efficacy, Safety
• Patients
• 200 patients, broad population, randomized to
  placebo
• Age 1-16 years
• Hematological malignancies or neuroblastoma
  undergoing either allogeneic or autologous HSCT
• Endpoints
• Incidence and duration of WHO Grade 3-4 oral
  mucositis
• Acute and long-term safety
• Doses established in Phase 1

COG Childrens Oncology Group
9
Palifermin Pediatric Development

• Common to All Drugs in Pediatric Oncology
• Similar to pegfilgrastim
• Palifermin-Specific Issues
• Change in standard therapy
• Competition with therapeutic agent trials
• Need to establish long-term safety

10
Palifermin Pediatric DevelopmentSummary and
Conclusions

• Positive benefit/risk profile based on approved
  adult indication
• Severe mucositis is an unmet medical need in the
  pediatric transplant population
• Pediatric development program with common and
  product-specific challenges
• Amgen shares the goal of making this drug
  available to children