european paediatric initiative experience in oncology l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
European Paediatric Initiative Experience in Oncology PowerPoint Presentation
Download Presentation
European Paediatric Initiative Experience in Oncology

Loading in 2 Seconds...

play fullscreen
1 / 35

European Paediatric Initiative Experience in Oncology - PowerPoint PPT Presentation


  • 292 Views
  • Uploaded on

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

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'European Paediatric Initiative Experience in Oncology' - salena


Download Now 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.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
european paediatric initiative experience in oncology

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

objectives of the regulation
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
main pillars
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)
main pillars4
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)
slide5

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

main pillars6
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)
new drugs before approval
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
on patent marketed drugs
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
orphan drugs
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

off patent drugs
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)
main pillars11
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)
paediatric investigation plan pip
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
paediatric investigation plans
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
pip waivers deferrals
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)

life cycle of a paediatric investigation plan
Life cycle of a Paediatric Investigation Plan

PIP

MA

Non-clin

Phase 1

Phase 2

Phase 3

Post Approval

1

Compliance

Modifications

Paediatric Committee

life cycle of a paediatric investigation plan16
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

applications and indications
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)
pip and waivers applications
PIP and Waivers Applications
  • August 2007 – April 2008:
    • All Indications: 326
    • PIP/Waiver applications: 178
  • Authorised products: 30 %

Update 3/18/2008

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

oncology pips21
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

class waivers
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
issues with pips waivers in paediatric oncology
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?
oncology pips24
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
paediatric condition indication
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
more issues
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
main pillars28
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)
transparency measures
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)
transparency measures30
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
other measures
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
public funding for studies on off patent drugs
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
take home messages
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
slide35
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