FDA Pediatric Oncology Subcommittee Meeting “Company Perspective”

FDA Pediatric Oncology Subcommittee Meeting

“Company Perspective”

Key Questions to Address(Company Perspective)

• Question #1-When in the development of a new oncolytic should pediatric studies be undertaken?

• Question #2-What factors influence the decision whether or not pediatric studies are undertaken?

• Question #3-Should pediatric studies be performed only by cooperative groups?

Key Questions to Address

• Question #1-When in the development of a new oncolytic should pediatric studies be undertaken?

• Question #2-What factors influence the decision whether or not pediatric studies are undertaken?

• Question #3-Should pediatric studies be performed only by cooperative groups?

Historically When Are Pediatric Studies Performed?

Drug Date of Initial FDA Approval

Date of 1st Adult Study

Date of 1st Pediatric Study

Difference in Years Between Studies

Gemcitabine 1996 1991 Ongoing 10+

Paclitaxel 1992 1986 1993 7

Cladribine 1993 1984 1991 7

Irinotecan 1996 1993 (US) 1999 (US) 6

Temozolomide 1999 1992 1998 6

Docetaxel 1996 1992 1997 5

Tretinoin 1995 1988 1992 4

Topotecan 1996 1992 1993 1

Imatinib 2001 2001 Ongoing 1+

ASPHO Survey1

(Interim Results)

Percent of ASPHO RespondersWhen should pediatric studies be undertaken?

3%

57%

37%

3%

Before Adult Phase IDuring Adult Phase IAfter Adult Phase IOther

1Survey of 91 ASPHO Members-October 2002

Key Questions to Address

• Question #1-When in the development of a new oncolytic should pediatric studies be undertaken?

• Question #2-What factors influence the decision whether or not pediatric studies are undertaken?

• Question #3-Should pediatric studies be performed only by cooperative groups?

ASPHO SURVEY1-INFLUENTIAL FACTORS2

1. Pediatric preclinical data

2. Drug with new mechanism or target

3. Positive data from adult phase I or II

4. Availability of drug for pediatric studies

5. Other factors

1Survey of 91 ASPHO Members-October 20022Rate from 1-7; One being least influential

“Most Influential-#7”

05

101520253035404550

Preclinicaldata

Newmechanism

Adultexperience

Availability ofdrug

Other

#Re s

pond

ers

choo

sing

“7”

Key Questions to Address

• Question #1-When in the development of a new oncolytic should pediatric studies be undertaken?

• Question #2-What factors influence the decision whether or not pediatric studies are undertaken?

• Question #3-Should pharmaceutical companies conduct pediatric studies outside of cooperative groups?

ASPHO Survey1

Percent of RespondersShould Pharmaceutical Companies Conduct

Pediatric Studies Outside of Cooperative Groups?

37%

57%

6%

No Yes No Comment

1Survey of 91 ASPHO Members-October 2002

Comments- “No”• Patient numbers too small-direct competition with COG

studies• Definitely “no”; “That would be a terrible mistake”• Concerned about “conflict of interest”• Cooperative group(s) are cornerstone of our success

against pediatric cancer• More convincing if studies are done within Cooperative

group setting• Cooperative group mechanism in concert with industry

and the NCI, when necessary, should meet all industry and FDA requirements

Comments-“Yes”

• The Cooperative groups have a problem with congestion; Speed!

• Cooperative group is a monolith

• Any route necessary if it means getting phase I studies in children

• Resources and infrastructure

• Opportunity for smaller institution

“Company Prospective”

Early Pediatric Studies Late Pediatric Studies

Medical/ScientificSimilar disease processSimilar target expression(Novel mechanism)

RegulatoryPediatric Rule

Business DevelopmentFDAMA/BPCA

CMCFormulation-oralStability(Drug supply)

Toxicology“Unaccepted” toxicitiesUnusual target organs

Unmet Need

Each new agent needs to be considered separately(there is no standard approach)

Data ManagementCooperative group

Summary- “Company Perspective”• Strong shift towards not if, but when, should pediatric

studies be undertaken• Most pediatric oncologist believe studies should be

done early versus late– Company involvement is OK-But!– Perception that conducting studies outside cooperative groups

could speed up the process?

• Companies are showing increased interest in developing new agents in children– FDAMA and Pediatric Rule

• Many factors influence decision to conduct studies in children– Industry views are similar to those of pediatric oncologist, but

there are obvious differences

Questions-Discussion?

“Other Influential Factors”

• A company that is not overtly hostile towards pediatric studies (7)

• Favorable side-effect or toxicity profile (6)

• Unmet need (5)

• Ease of study (5)

• Foreign experience (4)

Recent/Ongoing Pediatric Phase I Studies

ABT-751 (ST) Arsenic Trioxide (L) BMS 247550 (ST)Clofarex (L) Carbo/Irinotecan (ST) DX-8951f (ST)Fenretinide (ST) Doxorubicin Liposome (ST) Flavopiridol (ST)Gadolinium Texaphyrin Cisplat/VP16/Bleo/Amifostine (GC) IT-Busulfan (BT)Iodine I131 MIBG (NB) Melphalan/Buthionine Sulfoximine IrinotecanOxaliplatin (ST) R115777 PS-341SCH 66336 (BT) Squalamine/Carbo (ST) SU5416 (BT)Temozolomide/O6BG Thiotepa/Carbo/Topotecan (ST) Irinotecan/VCR (ST)XR 9576 (ST) STI571 (ST) Holmium Ho 166

IL-2 Expanded CD8 Cells (NB) Rituximab-Glucan MoAb 3F8 (NB) hu14.18/IL-2 (NB)MoAb Ch14.18/IL2 (NB)