Orphan Café, 8 december 2011 Presentation by Lugdivine Le Dez (Alexion) & Laura Gutierrez (Celgene)

1. JOINT RARE DISEASES / ORPHAN
MEDICINAL PRODUCTSTASK FORCE
A collaborative initiative with national trade associations and
policy developments at EU level.
Lugdivine Le Dez (Alexion)
Laura Gutierrez (Celgene)

2. Agenda
I. Presentation of the joint taskforce
II. Cooperation with national OD groups:
◦ Objectives, rationale, proposal, expected
outcomes
III. Highlight of EU policy developments

3. I. Presentation of the joint
taskforce

4. European member companies of all sizes that
have either developed or intend to develop
orphan drugs
Members of EBE and/or EuropaBio,
4 Meetings per year
Name of active member companies: Actelion, Alexion,Astra Zeneca,
Biomarin, Celgene, CSL Berhing, Dompé, Genesis Pharma, Genzyme,
GSK, Novartis, Novo Nordisk, Merk Serono, Orphan Europe, Pharma
Mar, Pfizer, Shire.
47
companies
What is the Joint Task Force?

5. Objectives of the
Joint Task Force
 Contribute to the development of EU rare diseases-related policies
and regulatory frameworks
 Work towards a harmonised implementation of EU legislation and
regulatory guidelines for OMPs
 Improve timely access to therapies for all rare disease patients
across the EU
 Raise awareness about the economic and social value of OMPs

6. Why the EU matters?
• Member States’ individual responsibilities:
 Health care financing
 Pricing and reimbursement of drugs
• Influences the political agenda of the individual EU
countries:
 Laboratory of ideas
 Meeting point of national authorities: Exchange of
best /worst practices among Member States
• Regulation of the pharmaceutical sector:
 Marketing Authorizations
 Clinical Trials rules
 Orphan Drugs Regulation (ME)
 Intellectual Property (Data protection, SPC)

7. Joint taskforce 2011-2012 priorities
• Industry input in the CAVOD process and Mechanism of
coordinated access to ODs
• Exceptions for OMPs both at EU and national level and establish
links with national trade association.
• National Plans for Rare Diseases
ACCESSTO
OMPs FOR
PATIENTS
• Build tools to communicate the values and specificities of the
OMP business models
• Implementing a tailored outreach (educational) programme mainly
targetted at EU audiences
VALUE AND
REPUTATION OF
THE RARE
DISEASE
BUSINESS
MODEL
• Ensure that the EU legislative and regulatory frameworks continue
to be appropriate and predictable for OMP developers
• Ensure that a consistent framework for registries is implemented
at national level
LEGISLATIVE
AND
REGULATORY
ASPECTS OF
OMPs

8. II. Cooperation with national
OD groups
A collaborative approach with national trade
associations

9. Creating interaction
EU Orphan
Drug
Taskforce
National
trade
associations

10. Main objectives
- Enhancing cross-communication
- Information sharing / best practice sharing
- Supporting local efforts/crisis when
needed

11. • European
Commission
• European
Parliament
• EU Council
EU
Regulators • EMEA/COMP
Other
Stakeholders
• Patient group
• Healthcare
professionals
• Academia
National
trade
associations
An new partner
EU
institutions
Joint EBE-EuropaBio
Task Force

12. Rationale
- Relevance of MS policy work on EU policy and vice
versa
- Dominoes effect of local policy/cost containment
measures on other MS
- Common objective to orphan drug policy
- Unstable EU economic/financial environments needing
sustained policies for ODs

13. Interaction process
EU Orphan DrugTaskforce National trade associations
• Share with you with tools we
developed to promote the value of
ODs, and punctual EU policy
updates
• Organise a yearly “get together” in
Brussels with all national relevant
leaders to share best practices and
align on common goals.
• Share information about major
national political and legislative
decisions that can have an impact
on orphan medicines in your
country but also in the rest of
Europe
• Share tools/concepts
• Send your group representative to
the yearly meeting in Brussels
• Ensure an industry unified approach to OD policy
developments
• Ensure EU support is provided when requested to
reinforce local lobby
• Ensure all parties (EU/Local) are ready to react in time

14. Tools to update you on ongoing EU
work and to promote national plans

15. Tools to communicate OD specificities

16. The budget impact is
estimated to have grown from
0% in 2000 to 3.3% by 2010
From 2010 to 2016, the rate
of growth is likely to slow
and will reach a plateau of
approximately 4.6%
3.3%
4.6%
Orphan Drug Budget Impact
The budget impact of orphan medicines in Europe has grown steadily over the 10 years
since the introduction of the orphan drug legislation in 2000, but growth is predicted to
slow and plateau over the next decade

17. III. Key highlight of EU policy
developments

18. Highlights of EU ongoing policy
developments
EU
policy
Follow up to
implementation
of National
Plans
CAVOD
MOCA
ClinicalTrials
Directive
Transparency
Directive (P&R)
Directive on
patients’ rights
in cross-border
healthcare
EUCERD

19. Highlights of EU ongoing policy
developments
EU
policy
Follow up to
implementation
of National
Plans
CAVOD
MOCA
ClinicalTrials
Directive
Transparency
Directive (P&R)
Directive on
patients’ rights
in cross-border
healthcare
EUCERD

20. Council Directive 89/105/EEC on P&R
processes– “Transparency” Directive
 Does not affect national decisions regarding prices
 Sets rules for decision regarding P&R (time-limits, transparency, and right to appeal)
Timelines:
◦ December 2011/January 2012: New legislative proposal expected end.
◦ Debate in the EP and Council is foreseen in 2012;
◦ Implementation by Member States in 2013/2014.
Expected content:
- Shortening of timelines for both generics (15/30 days) and innovative medicinal
products (60/120 days).
- HTA in the scope
- Results of the marketing authorization (quality, safety, efficacy, bioequivalence) shall
not be reassessed in HTA decisions

21.  Concerns
 Instrumentalisation by Member States to facilitate cost-containment
measures and increased international reference pricing
 Demands by European Parliament for harmonisation of prices
Council Directive 89/105/EEC on P&R
processes– “Transparency” Directive

22. Highlights of EU ongoing policy
developments
EU
policy
Follow up to
implementation
of National
Plans
CAVOD
MOCA
ClinicalTrials
Directive
Transparency
Directive (P&R)
Directive on
patients’ rights
in cross-border
healthcare
EUCERD

23. Background: Clinical Added-Value of Orphan
Drugs (CAVOD)
Initiated by Eurordis, included in the recommendations of
High Level Pharmaceutical Forum
◦ Possible exhange of knowledge on the scientific assessment of
the clinical added value of orphan drugs (CAVOD)
 Original objectives – speed patients access
◦ Make the most of evidence on Clinical AddedValue of Orphan
Drugs gathered by EMA
◦ Coordinate payers requirements for additional data
 European Commission commissioned E&Y to identify
implementation options

24. Main purpose of the
CAVOD study
 PURPOSE OF THE STUDY
• Identify and assess the possible options for the creation
of a mechanism for the exchange of knowledge between
Member States and European authorities on the scientific
assessment of the relative effectiveness of orphan medicines (to
be implemented, if possible, from 2011)
 PURPOSE OF THE MECHANISM
• To facilitate MS informed decision on the scientific
assessment of the clinical effectiveness of an orphan drug
• To contribute to the development of a continuum between pre-
market authorization practices (clinical development) at EU
level and post-marketing authorizations practices at member
state level
• SOURCE: European Commission

25. CAVOD: a potential tool for better
access to orphan drugs
 Based on the initial opinion of the COMP and CHMP at the time of
orphan designation, which
 includes an evaluation of the significant clinical benefit of an OMP –
which is confirmed at time of MA

26. CAVOD:The E&Y report
 A state of play of regulatory processess
and HTAs for ODs in Europe.
 An identification of the data collection
which could be accepable for assesing
relative effectiveness of ODs.
 A proposal for a collaboration mechanism
between regulatory and HTA bodies for
OD assessment.

27. Sources: Draft Backgroung review, EUnetHTA JA WP5: Relative Effectiveness Assessment (REA) of Pharmaceuticals; April 2011
EUnetHTA WP4 – HTA Core Model for Medical and Surgical Interventions, Dec ember 2008
(1) Approach aligned with the EUnetHTA JA WP5:
REA of Pharmaceuticals, Draft Background review,
April 2011:. WP5 model
to be particularly considered as being part of
rare diseases’ specificity
► The type of evidences (1) covered by the clinical added value are based on
the EUnetHTA JA WP4 & WP5 & HTA core model and adapted to the
specificity of orphan drug
► 1. Health problem and current use of the technology
► 2. Description and technical characteristics of technology
► 3. Safety
► 4. Effectiveness
► 5. Costs, economic evaluation
► 6. Ethical aspects
► 7. Organizational aspects
► 8. Social aspects
► 9. Legal aspects
Data to measure the CAVOD
already considered
as part of EMA scope

28. E&Y: Interaction process
EUnetHTA-CAVOD/EMA
► The objective of the interaction between EUnetHTA-CAVOD and EMA is to build a bridge and
develop a continuum between pre-market authorization practices (clinical development) at EU
level and post-marketing authorizations practices at member state level.
► Through this process, the National HTA bodies through EUnetHTA are engaged collectively and
bring their experience together to give inputs and valuable requirement to the EMA prior to the
Risk management plan.
► Member states will be able to contribute to the Risk management plan.
Evidence
requirement
gathering from
HTA bodies
Writing of
recommendation
paper
Identification
of the project
manager PM
EUnetHTA-CAVOD
Exchange of
information with
the rapporteur of
OD at the CHMP
Marketing Autorisation review process, prior to CHMP opinion
Exchange of information with
EUnetHTA-CAVOD PM *
One EUnetHTA-CAVOD PM for 4 days (FTE)
EMA
•Focused on HTA expectations for evidence generation
• Based on national HTA bodies experience of the disease
&/or drug
Recommendation
paper for EMA
* Discussion to consider
at the CHMP committee
including EUnetHTA-
CAVOD PM ?

29. CAVOD:The E&Y Report
Time
CHMP opinion, T0
EC marketing
authorisation
T0 + 90 days
T0+ΔT
(after 3 to 5 years, flexible
depending of the disease)
Period 1:
for EMA / EUnetHTA
coordination
Period 2:
for simple
Compilation
report &
evidence
generation plan
Period 3:
for follow up of the
evidence generation plan
Period 4:
relative
effectiveness
assessment
Protocol
assistance
Significant Benefit, COMP

30. E&Y report: Concerns
 Involvement of EUnetHTA, namely:
◦ Involvement of HTA bodies in the regulatory
process -> impact on MA.
◦ Interactions between EMA and HTA not well
defined  additional hurdles for access?
◦ Lack of expertise in OD of HTA bodies.

31. CAVOD: Next steps
 Rare Diseases stakeholder community
• Industry comments under development Dec
2012
• EUCERD drafting group
• Workshop tentatively scheduled for March 2nd
2012
• EUCERD opinion document to be adopted
June 2012

32. Highlights of EU ongoing policy
developments
EU
policy
Follow up to
implementation
of National
Plans
CAVOD
MOCA
ClinicalTrials
Directive
Transparency
Directive (P&R)
Directive on
patients’ rights
in cross-border
healthcare
EUCERD

33. Mechanism of coordinated access to ODs-
Background
 Sept 2010: Launch of “Tajani initiative” including all
relevant stakeholders in pharmaceutical sector.
 3 platforms aimed at developing recommendations
focusing on specific issues:
◦ Ethics andTransparency
◦ Access to medicines in the least developed countries
◦ Access to medicines in Europe, including a platform on
Mechanism of coordinated access to orphan medicinal
products.

34. 34
Mechanism of cooordinated access
to ODs
 Project vision: The coordination between stakeholders and
Member States at EU level to provide real access to a real
solutions (orphan medicinal products) for real
patients with real unmet medical needs, for which these
solutions would otherwise be out of reach – in an affordable
and sustainable way (-> “real life access”).
 Project objective: Designing a concrete operational manual
of coordinated real access for stakeholders and Member
States to achieve the vision irrespective of the local
conditions starting with the identification of the unmet
medical need and the possible answers (phase zero).

35. 35
Mechanism of coordinated acces to ODs -
Project Methodology
Mechanism of coordinated access to
orphan medicinal products
WP1
Identifying and
assessing a relevant
orphan drug
(Assessment/evaluative)
WP2
Selection of target
population and
mechanism of funding
(Structural access)
WP3
Treatment
(Individual access)
#1
operationa
l step
#2
operationa
l step
#1
operationa
l step
#2
operationa
l step
#2
operationa
l step
#1
operationa
l step
#1
impl.
activit
y
#2
impl.
activit
y


36. Reminder
 Objective: an industry unified approach
when dealing with Orphan Drug Policy
 Proposed next steps:
◦ Sharing of messages/tools
◦ Regular updates
◦ Yearly meeting (date tbd)
 Your feedback on cooperation?

37. Thank you for your attention!

38. Back-up slides

39. Directive on patients’ rights in
cross-border healthcare
 Directive on patients’ rights in cross-border healthcare Adopted by the European Parliament
(EP) on 19 January and by the Council on 28 February. Member States have until 25 October
2013 to implement it
 The EP managed to include rare diseases in the scope of the directive, which had been opposed
for long by MS
 Key elements of the adopted text:
◦ Prior authorisation system (could only be refused on obvious grounds)
◦ Reimbursement (a patient being treated in another Member State should be reimbursed up to the amount
of the reimbursement anticipated by his own national health system for similar treatment)
◦ Diagnosis and treatment of rare diseases (support to EU Member States in cooperating in the development
of their diagnosis and treatment capacity )
◦ Information to patients (obligation to set up a kind of one-stop shop)
◦ European reference networks (objectives: facilitate mobility of expertise (virtually or physically); develop,
share and spread information, knowledge and best practice; foster developments of the diagnosis and
treatment of rare diseases)
◦ HTA cooperation (new legal basis for an improved HTA-related cooperation between EU Member States)
◦ Prescription recognition (a prescription issued in another EU country will be recognised in a patient's
country of residence and vice versa)

40. WP 1 WP 2 WP 3
BELGIUM Ri De Ridder 2
Francis Arickx 1 2 3
Catherine Adriaens 1 2
Marleen Mortier 2
Céline Hermans
Mireille Pierlet
Diane Kleinermans 3
AUSTRIA Christine Leopold 3
Florian Bachner
ESTONIA Dagmar Ruutel 1
FINLAND Sari Ekholm
Jyrki Vanakoski 1
FRANCE Danielle Golinelli
Pierre Pribile
Patrick Cayer Barrioz 1 2 3
Arlette Meyer 1 2
Catherine Choma
Nadine David
Renaud Morin
GREECE Lena Katsomiti
HUNGARY M Szabados
Mi Palosi
Claudia Habl 1 2 3
Sabine Vogler

41. ITALY Pietro Folino Gallo
Paolo Siviero 2
MALTA Jennifer Farrugia 1
Isabelle Zahra-Pulis
NETHERLA
NDS
Hugo Hurts
Huub Kooijman
HJJ Seeverens
POLAND Jakub Adamski 2
PORTUGAL Ines Ramos 2
SPAIN Mercedes Vallejo
Martinez
2
SWEDEN Anna-Marta Stenberg
Maria Storey 1

42. EFPIA Katia Finck 2 3
Wills Hughes-Wilson 1
Ana Palma 1
Kevin Loth 1
Adam Heathfield 2 3
Laura Gutierrez 1
Enda Scott 2 3
Thomas Cueni
François Bouvy
EGA Greg Perry
Ilina Markova
EuropaBio Ludovic Lacaine
GIRP Monica Derecque-Pois
Martin Fitzgerald 2 3
EPF Yann LeCam 1 3
Ariane Weinman
Flaminia Macchia 1 3
AIM Heidi Goethals 2
ESIP Anna Bucsics 2
Hans Seyfried 2
CPME Oscar Arias 3
Birgit Beger
Synnove Lindemalm 1 3

43. COMP Elodie Carmona
Dominik Schnichels
SANCO Jerome Boehm
Anders Lamark Tysse
Nathalie Chaze
Patricia Brunko
Mirjam Soderholm
MARKET Jean Bergevin
Jan Willem Verheijden
ENTERPRISE 1 2 3
Thomas Heynisch
Christophe Roeland
Valerie Vanhoeck
Giulia DelBrenna
Laura Nistor
Aurelie Vandeputte
Eminet 1 2 3