1 / 35

European Paediatric Initiative Experience in Oncology

European Paediatric Initiative Experience in Oncology. Dr Agnès Saint Raymond & Dr Ralf Herold Scientific Advice, Paediatrics and Orphan Drugs Sector European Medicines Agency, EMEA FDA April 16 2008. Objectives of the Regulation . Improve the health of children

salena
Download Presentation

European Paediatric Initiative Experience in Oncology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. European Paediatric InitiativeExperience in Oncology Dr Agnès Saint Raymond & Dr Ralf Herold Scientific Advice, Paediatrics and Orphan Drugs Sector European Medicines Agency, EMEA FDA April 16 2008

  2. Objectives of the Regulation • Improve the health of children • Increase high quality, ethical research into medicines for children • Increase availability of authorised medicines for children • Increase information on medicines • Achieve the above • Without unnecessary studies in children • Without delaying authorisation for adults

  3. Main pillars • Creation of a Paediatric Committee • Measures for new/patented drugs • Measures for off-patent drugs • Paediatric Investigation Plans • Many other measures (information and transparency)

  4. Main pillars • Creation of a Paediatric Committee • Expert Committee • Mix of Academics and Agencies employees, including paediatric oncologists • Meeting monthly at EMEA • Scientific decisions • Measures for new/patented drugs • Measures for off-patent drugs • Paediatric Investigation Plans • Many other measures (information and transparency)

  5. Paediatric Committee 1 elected Chair 5 members from Approval Committee (CHMP) 22 representatives from other Member States 3 Patients/families’ representatives* 3 Health Professionals representatives* *still to be appointed

  6. Main pillars • Creation of a Paediatric Committee • Measures for new/patented drugs • Measures for off-patent drugs • Paediatric Investigation Plans • Many other measures (information and transparency)

  7. New drugs before approval • Obligation to submit results of agreed Paediatric Investigation Plan (PIP) • At time of Marketing Authorisation Application, OR Deferral of studies, OR Waiver of development • Reward: 6-month extension of the patent • Conditions: • compliance with PIP • results in product information • approval in all Member States

  8. On-Patent marketed Drugs • Obligation to submit results of agreed Paediatric Investigation Plan (PIP) • When applying for new indication, new route of administration, and/or new formulation • OR deferral of studies, OR waiver • Reward: 6-month extension of the patent • Conditions: • compliance with PIP • results in product information • approval in all Member States

  9. Orphan drugs • Among orphan drugs, 15-20% are for diseases only affecting children, 55% for diseases affecting both adult and children* • Orphan drugs receive 10 years of market exclusivity in EU • Orphan drugs must submit a Paediatric Investigation Plan • Orphan drugs can get 2 additional years of exclusivity when they comply with PIP * EU orphan designation data

  10. Off-patentdrugs Paediatric Use Marketing Authorisation (PUMA) • Optional • Covers Paediatric Indication and Formulation • Need for agreed Paediatric Investigation Plan • Need for compliance and results in Product information • Incentive: Data protection of 10 years (as for new products in EU)

  11. Main pillars • Creation of a Paediatric Committee • Measures for new/patented drugs • Measures for off-patent drugs • Paediatric Investigation Plans • Many other measures (information and transparency)

  12. Paediatric Investigation Plan (PIP) • Paediatric Investigation Plan proposed by company • By end of phase 1 for new products • Plan is discussed, modified, and agreed/refused by Paediatric Committee • Followed by EMEA Decision • Binding on company

  13. Paediatric Investigation Plans • Define necessary data on Quality, Safety and Efficacy for use in the paediatric population (0 – 18 years) • No explicit link with adult indication • Specify development timelines, including deferral of studies • Define age-appropriate formulation • Results according to agreed plan serves as basis for approval

  14. PIP Waivers/Deferrals On request from applicant or initiative of Paediatric Committee, for all or part of the paediatric population: • Waiver of development for ‘classes’ of indications, or for a specific product • Deferral of initiation of studies and/or completion Development is most often a combination of a plan with deferrals and waivers (population subset)

  15. Life cycle of a Paediatric Investigation Plan PIP MA Non-clin Phase 1 Phase 2 Phase 3 Post Approval 1 Compliance Modifications Paediatric Committee

  16. Life cycle of a Paediatric Investigation Plan PIP MA With deferral Non-clin Phase 1 Phase 2 Phase 3 Post Approval 1 Modifications Compliance Paediatric Committee

  17. Applications and Indications • Each PIP corresponds to an active substance (or a combination) from a company • Each PIP usually covers more than one indication (e.g. high grade glioma and neuroblastoma)

  18. PIP and Waivers Applications • August 2007 – April 2008: • All Indications: 326 • PIP/Waiver applications: 178 • Authorised products: 30 % Update 3/18/2008

  19. PIP Therapeutic areas (%) • CNS 6 • Cardiovascular 10 • Oncology 14 • Anti-infectives 10 • Endocrinology / metabolism 21 • Immunology / vaccines 11 • Other 28

  20. Oncology PIPs* • Active substances • Total 18 • New: 9 • Authorised: 9 • Cytotoxic / established / conventional: 9 • Non-cytotoxic / innovative: 6 • Supportive (antiemetics, growth factors) 3 • Written requests: 8 * Exclude full Waivers Update 3/18/2008

  21. Oncology PIPs* • Number of conditions / indications in oncology (15 active substances): • Total: 52 • Adult condition only 24 • Paediatric condition only 26 • Front line-treatment 11 • Relapse treatment 15 • Adult and paediatric 2 * Excludes full waivers

  22. Class Waivers • Published: • Oropharyngeal epithelial cancer • Lung cancer (small cell and non-small cell) • Basal cell carcinoma • Breast carcinoma • Ovarian carcinoma • Endometrial carcinoma • Prostate carcinoma • Hairy cell leukaemia • Multiple myeloma

  23. Issues with PIPs/Waivers in paediatric oncology • Low incidence for condition but exists • Definition of condition • Wider name = extended scope • Lower age range for studies: • Glioma, neuroblastoma, rhabdomyosarcoma • Which is the appropriate cut-off: 0 – 6 mo – 1 – 2 - 3 years? • Which minimal age for relapse / refractory disease?

  24. Oncology PIPs • Paediatric trials for 15 active substances: • Completed 17 • Proposed, ongoing 6 • Total per active substance ~ 1.5 • Collaborative paediatric oncology group ~ 6 • Proposed and planned trials • Phase 1/2 4 • Phase 2 single arm 10 • Phase 3 4 • Combination therapy studies 8 • Additional to Written Requests (n=3) 2

  25. Paediatric condition/indication • Rhabdomyosarcoma 3 • Non-RMS soft tissue sarcomas 2 • Ewing sarcoma 2 • Neuroblastoma 3 • High-grade glioma (HGG) 5 • Brainstem HGG 1 • Leukaemia 2 • Lymphoma 2 • Carcinoma 2 • Melanoma 2 • ‘Any solid tumours’ 3 • First-line treatment 10 • Treatment of relapse or refractory disease 9

  26. More Issues • No corresponding development in adults (no proof-of-concept) • Neonates: waiver very often requested • Non-clinical data : highly variable level of details • Models of paediatric tumours? • Study design choice • Studies deferred not described: Lack of overall strategy

  27. Main pillars • Creation of a Paediatric Committee • Measures for new/patented drugs • Measures for off-patent drugs • Paediatric Investigation Plans • Many other measures (information and transparency)

  28. Transparency measures PUBLIC ACCESS to: • Decisions on Paediatric Investigation Plans • Summary of content • Timelines • Results in Product Information • Publication of Assessment Reports (public outcome of evaluation)

  29. Transparency measures PUBLIC ACCESS to EU Database of all clinical trials (called EudraCT): • protocol-related information • results-related information • All trials with at least a study site in EU • All those performed outside EU if included in a Paediatric Investigation Plan

  30. Other measures • Establishment of an EMEA network of paediatric research networks (in particular paediatric oncology groups e.g. SIOP, ITCC) • Inventory of all paediatric uses of medicines in Member States • To help define ‘paediatric needs’ for future Paediatric Investigation Plans

  31. Public funding for studies on off-patent drugs Off-patent drugs on EMEA Priority List of about 60 drugs • EU funding (Framework Programme) ~ 20-30 million Euros available in 2007 • 5 projects funded • New call for proposals in July 2008

  32. TAKE HOME MESSAGES • Successful implementation • Paediatric oncology as a model: • Consider Mechanism of action/Target of a drug rather than Adult indication • Lack of Proof of concept in adults/ in children • Lack of models of paediatric tumours • Age groups to be included in trials • Weak level of evidence proposed • Collaborative approach highly needed

  33. CHMP: Committee for Human Medicinal Products (EMEA ‘approval’ Committee) • CT: Clinical Trial(s) EMEA: European Medicines Agency (ww.emea.europa.eu) • EU: European Union • EUDRACT: European Database of Clinical Trials European Commission (pharmacos.europa.eu) • GCP: Good Clinical Practice • ICH: International Conference on Harmonization • MA: Marketing Authorisation (Drug Approval) • MS: Member State • PIP: Paediatric Investigation Plan • PUMA: Paediatric Use Marketing Authorisation

More Related