Kerstin Westermark

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Treatment of Rare Diseases and EU Legislation
Prag, May 21, 2009 "Role of COMP and support of
research and development of drugs with orphan
medicinal product designation in the EU"

• Kerstin Westermark
• Prof., Senior expert, Medical Products Agency,
  Sweden
• Chair, Committee for Orphan Medicinal Products,
  EMEA

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Who wants to be an Orphan?
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Why an Orphan Regulation?

• Regulation (EC) No 141/2000 of the European
  Parliament and of the Council on Orphan Medicinal
  Products of 16 December 1999
• Persons suffering from rare conditions should
  be entitled to the same quality of treatment as
  other patients
• But
• the pharmaceutical industry would be unwilling
  to develop the medicinal product under normal
  market conditions
• As
• some conditions occur so infrequently that the
  cost of developing and bringing to the market a
  medicinal product () would not be recovered by
  the expected sales

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Which Incentives in EU for Orphan designated
Medicinal Products (OMP)?

• Market Exclusivity in the EU
• - 10 years for all orphan medicines (from
  marketing authorisation)
• 2 years if Paediatrics Investigational Plan
  (PIP) results included in the MA and reflected in
  the SPC
• Fee reductions for OMP development
• Application for OMP Designation free of charge
• Protocol assistance and follow up from the EMEA
  free of charge
• Application for Marketing Authorisation free of
  charge for Small and
• Medium-sized Enterprises (from 2009)
• Extended incentives for SMEs in post
  authorisation
• EU marketing authorisation through unique
  centralised procedure
• Priority to EU Research - Framework programs
• Access to Member States Incentives (EC inventory)

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EMEA European Medicines Agency (EMEA)

• Coordinates evaluation and supervision of
  medicinal products
• throughout the EU
• Brings together scientific resources of the 27 EU
  Member States network of the national competent
  authorities
• Has around 100 working groups/parties and access
  to a network of ca 4000 European experts
• Works through 6 Committees
• - CHMP Committee for Medicinal Products for
  Human Use
• - COMP Committee for Orphan Medicinal Products
• - PDCO Paediatric Committee
• - CAT Committee for Advanced Therapies
• - HMPC Herbal Medicinal products Committee
• - CVMP Committee for Veterinary Medicinal
  Products
• The committees give Opinions
• The EU Commission gives Decisions

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Committee for Orphan MPs (COMP)
Patients' representatives (3)
EMEA members (3)
Experts from Member States (273)
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Tasks of the COMP

• Examine applications for designation of a
  medicinal product as an orphan medicinal product
  (OMP)
• Assist the Commission in drawing up guidelines
• Assist the Commission in liaising internationally
  and with patient support groups
• Advise the Commission on a policy on orphan
  medicinal products for the EU

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• Examine applications for designation of a
  medicinal product as an orphan medicinal product
  (OMP)
• What was expected in year 2000?
• Ca 15 applications
• Four-five1 day meetings/year
• What was the result?
• More than 100 applications/year
• Eleven 2-day meetings/year

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Criteria for Orphan Designation

• SERIOUS CONDITIONS
• (life threatening, chronically disabling)
• RARE lt 5/10.000 individuals in the EU
• or
• LACK OF RETURN ON INVESTMENT
• NO SATISFACTORY TREATMENT
• or
• "SIGNIFICANT BENEFIT"
• (A clinically relevant advantage or
• a major contribution to patient care)

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Protocol assistance

• Protocol assistance ? scientific advice
• for companies developing OMPs
• Questions on quality-efficacy-safety
• Questions on significant benefit
• Company position required
• SAWP (Scientific Advice Working Party) provides
  answers COMP represented by 3 members
• CHMP adopts answers
• COMP involved/adopts answers on significant
  benefit
• Follow-up Protocol Assistance possible

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Protocol assistance - improved chances for a
successful marketing authorisation application!

• Orphan Drug development requires
• Flexibility at Regulatory level
• Potential for alternative approaches
• Strive for efficiency
• But - No new methods for rare disorders

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Guidance documents www.emea.europa.eu

• Guideline on the Format and Content of
  applications for designation as orphan medicinal
  products and on the Transfer of designations from
  one sponsor to another, 9July 2007 (ENTR/6283/00
  Rev 3)
• Guideline on Elements Required to Support the
  Medical Plausibility and the assumption of
  Significant Benefit for an orphan designation (In
  public consultation)

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Guidance Documents (cont'd)

• Points to consider on the calculation and
  reporting of the prevalence of a condition for
  orphan designation (EMEA/COMP/436/01)
• Guideline on clinical trials in small populations
  (CHMP/EWP/83561/2005)
• several CHMP guidelines (general and
  disease/drug specific)

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Websites

• EMEA www.emea.europa.eu
• (orphan drugs, guidelines, EPARs etc.)
• DG Enterprise www.ec.europa.eu/enterprise/pharmace
  uticals/regiater/index.htm
• DG Research www. cordis.lu

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EMEA Marketing Authorisation Centralised
procedure

• Mandatory for orphan designated products
• One single marketing authorisation application to
  the EMEA
• A single evaluation by the Committee for
  medicinal products for Human Use (CHMP)
• If quality, safety and efficacy sufficiently
  proven positive opinion
• Opinion sent to EU Commission transformation
  into a single marketing authorisation valid for
  the whole of EU

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10 (2) years of Market exclusivity

• Protection against
• similar products (structure/mechanism of action)
  for same indication
• Three derogations
• Sponsors consent
• Lack of supply
• Clinical superiority

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International Co-operation (Confidentiality
arrangements existing) Facilitating Cooperative
Efforts on the Orphan Regulatory Process

• EU (EC and EMEA) and the US FDA/DHHS
• (actions ongoing)
• EU (EC and EMEA) and Japan MHLW/PMDA
• (actions planned)
• EU (EC and EMEA) and Health Canada
• (actions started)

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Since November 2007Common Application Form
EMEA/COMP FDA/OOPD for Orphan Medicinal
Product designation

• A common form to simplify administrative process
• First step in harmonising administrative
  practices
• BUT
• Different regulations and procedures
• - Different criteria/requirements (prevalence
  threshold, significant benefit)
• - Different approaches (definition of condition)
• - No single opinion EU and US

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EMEA/COMP-FDA/OOPD(currently ongoing/planned)

• Regular contacts monthly teleconferences
  EMEA-FDA
• Exchange of information on ongoing orphan
  designation application procedures between the
  two agencies
• Annual reports on development
• Timeline and structure harmonisation
• Guidelines on orphan designation
• Existing EMEA/COMP guidelines
• Proposal for future discussion and harmonisation
  of common terms

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TOMORROW Facilitating Cooperative Efforts on
the Orphan Regulatory Process The Global
Approach

• Creating an international forum for discussion on
  the harmonisation of terminology and concepts
  related to designation
• Sharing international expertise and discussing
  divergent opinions
• Creating an international network of experts to
  be used for designation
• Discussing a global approach for stimulation of
  research linked to orphan designation
• Global administrative harmonisation

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EU Orphan regulation 141/2000 A SUCCESS STORY

• Before the EU - 27 different marketing approval
  procedures for every new drug
• Before the EU Orphan Regulation almost no
  development of drugs for rare diseases/conditions
• Today, after more than 9 years of the Orphan
  Regulation
• 937 applications for orphan designation/ 648
  positive opinions/ 231 withdrawals/ 13 negative
  opinions
• Today, after more than 9 years of the Orphan
  Regulation
• - 53 marketing authorisations for orphan drugs
• - via centralised procedure
• 1 procedure for 27 Member States
• Update May 6, 2009

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EU Orphan Regulation 141/2000 - Opportunities
for patients with rare conditions

• Potential benefits for 30 milj. European patients
  with rare conditions
• Potential benefits for neglected diseases, e.g.
  tbc, malaria, leishmaniasis rare in the EU
  prevalent in the rest of the world
• To date, 53 orphan medicinal products have been
  given marketing authorisation, a main part
  innovative drugs from micro-, small and medium
  sized enterprises (e.g. gene therapy for SCID)
• Potential benefit for the understanding of and
  drug development for common diseases
• "Learning from the Rare" (William Harvey)
• but
• Challenges
• Profitability Costs - Avalibility

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How can COMP contribute- What's on/What's next?

• COMP members in Scientific Advice Working Party
  (SAWP) "full advice" not only significant
  benefit questions
• Increased collaboration/harmonisation between
  EMEA committees (COMP- CHMP-PDCO-CAT)
• Increased transparency in COMP opinions - COMP
  role in scientific assessment of "clinical added
  value" of OMPs
• Increasing role of COMP visavi stakeholders
  (patient organisations, industry, health care
  professionals/academia) regular meetings/focus
  groups/conferences
• COMP members in EU Commission Rare Disease Task
  Force (RDTF) future Committee of Experts on
  Rare Diseases (CERD)
• COMP as advisors to the EU Commission (DG
  Enterprise/Sanco/Research (Rare diseases FP7
  priority Support fro clincial trials in phase
  I-II in designated OMPs 2009?
• COMP members as Member States "ambassadeurs" for
  Rare Diseases/Orphan Drugs (National plans
  National registries etc.)

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From challenge to solution? 4th Eurordis' survey
on OMPs availability in the EU(F.Bignami, MEDEV
meeting, Brussels, Jan. 2008)
ODD, PA, MA, Post-MA, Market Exclusivity, PS EU
level
EMEA EU
Availability for patients national level
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The way forward

• Conclusions and Recommendations from the High
  Level Pharmaceutical Forum (Oct. 2, 2008)
• http//europa.eu/pharmaforum/docs/final_conclusio
  ns_en.pdf
• - Commission Communication and Recommendation on
  Rare Diseases "Rare diseases - Europe's
  challenges" (Nov. 11, 2008)
• http//ec.europa.eu/health/ph_threats/non_com/rar
  e_10_en.htm
• Proposal for a COUNCIL RECOMMENDATION on a
  European action in the field of rare diseases
• http//ec.europa.eu/health/ph_threats/non_com/doc
  s/rare_rec_en.pdf

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