This document summarizes Solange Corriol-Rohou's presentation on the EMA's Adaptive Pathways initiative and the IMI ADAPT SMART project. The presentation discusses (1) the Adaptive Pathways approach explored by EMA and ADAPT SMART to facilitate early patient access to new medicines, (2) the goals and activities of the ADAPT SMART project, and (3) next steps to continue progressing the adaptive pathways approach.

1. Solange Corriol-Rohou, M.D.
ADAPT SMART deputy topic lead
AstraZeneca
14 June 2018
The new development paradigm as
explored through the EMA adaptive
pathway initiative and the IMI ADAPT
SMART project
A Sustainable, Multi-stakeholder Approach
from Research to Treatment-Outcomes

2. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Agenda
•The EMA Adaptive Pathways Initiative
•The IMI ADAPT SMART projects
•Next steps

3. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
THE EMA ADAPTIVE PATHWAY (AP) INITIATIVE
• Since 2014, the AP approach is part of the EMA efforts to improve timely access for
patients to new medicines
• AP is a scientific concept for medicine development and data generation to allow for
early and progressive patient access to a medicine
– iterative development, which either means:
• approval in stages, beginning with a restricted patient population then
expanding to wider patient populations
• confirming the benefit-risk balance of a product, following a conditional
approval based on early data (using surrogate endpoints) considered
predictive of important clinical outcomes
– gathering evidence through real-life use to supplement clinical trial data
– early involvement of patients and health-technology-assessment (HTA) bodies in
discussions on a medicine’s development
• The approach makes use of the existing EU regulatory framework for medicines, e.g.
use of scientific advice, compassionate use, conditional approval, disease registries,
PV tools/system

4. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/gen
eral/general_content_000601.jsp&mid=WC0b01ac05807d58ce
http://www.ema.europa.eu/docs/en_GB/document_library/Report/2017/02/WC500222153.pdf

5. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Concerns raised by stakeholders
• How will high unmet medical needs be defined?
• Will regulatory standards be relaxed?
• How will real world data be used and defined?
• How will companies be made to comply with data
requirements once their product is on the market?
• Will restricted medicines be restricted in practice?
Not all medicines are suitable for Adaptive
Pathways !!

6. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Workshop conclusions
• Broad agreement that the AP concept should focus on
meeting high unmet medical needs where data cannot
be acquired via RCTs
• Acknowledgment of the value of early involvement of
stakeholders, without putting patients at risk
• Recognition of the need for continued efforts to improve
access to medicines and ensure healthcare system
sustainability
• Based on the lessons learnt from the EMA pilot,
improvements have been made and the AP initiative is
now part of EMA processes

7. Solange Corriol-Rohou, M.D.
ADAPT SMART deputy topic lead
AstraZeneca
14 June 2018
What it is?
What has been achieved?
A Sustainable, Multi-stakeholder Approach
from Research to Treatment-Outcomes

8. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
MAPPs and ADAPT SMART
• The IMI ADAPT SMART
consortium established a
platform to facilitate and
accelerate the availability
of MAPPs* to all healthcare
stakeholders  science,
policy, political implications
• Outputs: recommendations
& proposals for future
research projects
*Medicine Adaptive Pathways to Patients

9. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
ADAPT SMART: a Coordination and Support Action
IMI 2 / CALL 4
• Funded by IMI-JU
• 01 June 2015 – 30 April 2018
• 24 EFPIA members
• 2 patients’ organisations
• 2 HAs, 2HTAs
• Payers as observers
• Total cost € 4 039 646
Project lead: H-G Eichler (EMA)
Deputy project lead: S. Corriol-Rohou (AZ)
Coordinator: A. Broekmans (Lygature)

10. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Governance
Patients
Eurordis / EPF
Yann le Cam / Nicola Bedlington
Regulators – EMA
Hans-Georg Eichler, Tomas Salmonson
Academia
CASMI / Lygature
Richard Barker / André Broekmans &
Pieter Stolk
Industry/EFPIA
AstraZeneca / Servier / Sanofi-Genzyme
Solange Rohou / Patricia Maillere /
Alicia Granados
HTAs
NICE / AIFA-EUnetHTA
Jacoline Bouvy/ Giovanni Tafuri
Payers (observers)
MEDEV
Ad Schuurman & Anna Bucsics
The Navigator Group

11. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Points to consider
• MAPPs is a life-span approach to learning: post-licensing
is as important as pre-licensing evidence generation
• What needs to be known before launch, what can wait
until post-launch?
• Consider the full spectrum of methodologies; are studies
doable?
• Does the evidence generation plan address the
information needs of all decision makers?

12. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
MAPPs and ADAPT SMART
• A 34 month journey, to explore a highly sensitive and
controversial concept
• All stakeholders of the health ecosystem
• To address key operational and strategic challenges to foster
access to beneficial treatments for the right patient groups at
the earliest appropriate time in the product lifespan in a
sustainable fashion
• Evolution and not a revolution, in a challenging environment
• Adaptive mindset to support a change in drug development
paradigm
• What has been achieved?
*Medicine Adaptive Pathways to Patients

13. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
How?
Unmet need
Timely access
Increase of the evidence-to-uncertainty ratio
Iterative development and assessment
Expansion of treatment eligible population
Adaptive pricing and reimbursement
Use of real world data
Ensure appropriate utilisation
Collaboration of all stakeholders
(sponsor, patients, regulators, HTAs, payers, health care providers)
Smartly designed combination of “building blocks”

14. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
When? …engagement criteria are met
1. Can we define a target population with a high unmet need? Does
the product hold sufficient promise to address the unmet need?
2. Can a prospective iterative post- (initial) marketing authorisation
development plan be proposed, developed, implemented and
agreed?
3. Are there workable tools to ensure appropriate product utilisation?
4. Are there workable ‘strategies’ for payers in case the product
under-performs?
5. Is there sufficient commitment and resources from relevant
stakeholders to ensure successful interactions?
6. Which critical aspects for pharmaceutical development would need
to be considered?

15. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
When? ...across entire product life-span

16. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Sustainability of innovation and
healthcare systems
• How can flexible pricing and reimbursement schemes contribute to a
MAPPs approach in a sustainable healthcare system?
• How could stakeholders effectively sustain resource mobilisation over
the lifetime of a medicinal product?
• How can the impact of a decision to disengage from MAPPs be
managed?
• Can the legal and ethical aspects of guiding the appropriate use of
medicinal products be dealt with in a sustainable fashion?
• How do the current exclusivity rights work for a product developed
under MAPPs?

17. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Project outputs
www.adaptsmart.eu
ADAPT SMART INFOGRAPHIC
• Proposals for future researches:
• Single arm studies
• Observational studies
• Indirect comparison &
Payers’ evidence requirements
• To be further explored:
• RWE generation & acceptance
• MEAs to facilitate adaptive
decision making
• Better patients’ and HCP’s
involvement

18. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
However..
• Conscious of the fact the AP/MAPPs approach is transformative
and disruptive
–Progress is expected to be slow
• We need to keep the momentum
–We need assets to show the approach is meaningful
• We need to communicate further
–To enhance acceptance of the MAPPs concept
• Dissemination is expected within and beyond Europe
–To integrate project outputs into everyday activities
• Project’s recommendations for future research proposals should
be seriously considered

19. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Next steps
•The EMA Adaptive Pathways Initiative
– Work in progress
•The IMI ADAPT SMART projects
– Keep th momentum

20. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
Post ADAPT SMART: some reflections for
keeping the momentum
• Communication: important not only to engage with all stakeholders but
also to look for opportunities to embed the learnings and principles of
MAPPs in development projects
• Patient and public voice: need to engage on an on-going basis, as
part of development projects and in further research projects
• Follow up on ADAPT SMART outputs: recommendations & proposals
for future research projects

21. © Copyright IMI ADAPT SMART | This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115890. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
ACRONYSMS
AP Adaptive Pathways
CSA Coordination and Support Action
EFPIA European Federation of Pharmaceutical Industry and Associations
EMA European Medicines Agency
IMI-JU Innovative Medicine Initiative-Joint Undertaking
HA Health Authority
HCP Health Care Provider
HTA Health Technology Assessment
MAPPs Medicines Adaptive Pathways to Patients
MEA Managed Entry Agreement
RCT Randomised Clinical Trials
RWD Real World Data
RWE Real World Evidence
WP Work Package