Simon Shohet PhD, Senior Director, Global Market access and Pricing, Ipsen Pharma Pricing & Market Access Congress 2017 22 February 2017 London

1. Simon Shohet PhD, Senior Director,
Global Market Access & Pricing, Ipsen.
Early evidence development for new
products –
planning for reimbursement success
World Evidence and Pharma Pricing & Market Access
Congress - London - February 2017
Note: This presentation represents the author’s views and the content is not
necessarily reflective of Ipsen’s company policy.

2. 2
European HTA and reimbursement processes are
complex – can early planning help address uncertainty?
“It is challenging even for those with considerable personal
experience in European HTA processes to establish what is really
happening in market access for new drugs. We recommend that
efforts should be directed toward improving transparency in HTA,
which should, in turn, lead to more effective processes”
Akehurst R.L. et al. Variation in Health Technology Assessment
and Reimbursement Processes in Europe
Value in Health (2017)
Simon Shohet, World Evidence and Pharma Pricing & Market Access Congress - London - February 21-23, 2017

3. Simon Shohet, World Evidence and Pharma Pricing & Market Access Congress - London - February 21-23, 2017
Pharma needs to adopt an agile business model that has
“market access” at its core
3
Parameters Old model New model
Organisation Silo’d and linear
Cross-functional and payer and patient
centric
People Vertical technical skill sets
Multi disciplinary and networked (T shaped).
Medics understand health economics,
marketeers understand trial design!
Global v local
governance
Centrally driven/top down
Delegated/decentralised/local empowerment
with clear governance and accountabilities.
Market access happens ‘on the ground’.
R&D process Regulatory-approval driven
Customer/payer driven – ‘agile’. Processes
to integrate stakeholders into R&D.
Evidence
dev’mnt
Late reaction to payer evidence
needs
Integrated approach (R&D, MA&P, MA,PA,
Franchises), anticipating evidence needs of
stakeholders early. Plan to capture RWE
Pricing
‘always maximize’ mantra
irrespective of volume
opportunity
‘Always optimise’. Adaptive, ‘elastic’, value-
based, willing to trade uncertainty
Launch
planning
Linear, disconnected.
Early engagement with multiple
stakeholders. Cross-functional & integrated.

4. Why ‘Early’ Market Access?
4 Simon Shohet, World Evidence and Pharma Pricing & Market Access Congress - London - February 21-23, 2017
“The ultimate objective of market access must be to enable payment for a
medicine at an optimal price for the manufacturer, at an acceptable cost
to the payer and which ensures access to patients.“
Internally, it means working collaboratively in a fully integrated way across the
development pathway, to generate a common evidence package that will
enable regulatory approval and positive HTA appraisal.
Phase I Phase II Phase III Filing Launch
Early market access is about ‘design for reimbursement’ up to pivotal
trial stage and ‘in-market’ collection of RWE. Includes in-house
development and assets in-licensed from other companies. In the
latter case robust early market access due diligence is critical.
In-market

5. 5
Many reasons for HTA negative appraisals can be
identified
• Treatment switching/cross overs
• Withdrawals
• Use of ‘Surrogate outcomes’ e.g. PFS
rather than ‘hard’ OS
• Imbalance of sub-groups in trial
• Results not generalisable to national
clinical practice
• Use of placebo rather than best
supportive care
• Comparator not standard of care
• Lack of measurement/ impact on
quality of life
• Uncertainty over clinical benefit
demonstrated
Simon Shohet, World Evidence and Pharma Pricing & Market Access Congress - London - February 21-23, 2017
• Safety / toxicity issues
• Lack of efficacy
• Model assumptions challenged
(e.g. time horizon, curve fitting)
• Use of indirect comparison
techniques (e.g. NMA)
• Cost effectiveness calculations
questioned (sources of costs,
assumptions, ICER calc)
• Budget impact unclear (e.g. market
shares)
• Lack of / inaccurate resource use
data
Sources: Author’s case study analysis of recent appraisals from NICE, IQWiG and HAS; Holmstrom et al. Payer/HTA
requirements in metastatic breast cancer ISPOR 18th Annual European Congress | 7–11 November 2015 | Milan, Italy: See
also Jonsson, B (2015), Molec Onc. (9), 1025 - 1033

6. 6
Several of these can be anticipated in trial design
and model planning
Reasons for HTA negative appraisals
Clinical trial related Modeling and cost/pricing
related
Potentially
within our
control
Surrogate outcomes
Imbalance of sub-groups
Results not generalisable
Use of placebo arm
Comparator not SoC
Choice of end points
QoL data collection
Model assumptions
Indirect comparison
techniques
Cost effectiveness
calculations / ICER
Budget impact
Resource use/treatment cost
data
Largely
outside our
control
Uncertain clinical benefit
Withdrawals
Safety / toxicity issues
Lack of efficacy
QALYs
Simon Shohet, World Evidence and Pharma Pricing & Market Access Congress - London - February 21-23, 2017
Cross-over

7. 7
Early planning best practice means anticipating payer
and regulatory questions concurrently
…as part of an integrated evidence plan
•Early advice
from payers
•Prototype
econ.
modelling
•Define
TPPs that
incorporate
payer value
features
(TVP)
•Design Ph II/b and Ph III
trials with agreed
comparators, end-points and
economic parameters
•Build-in Real World evidence
plans
•Power trials for sub-population analysis
•Plan to capture QoL to support utility
and humanistic value
•Timely preparation of
HTA dossiers tailored to
each HTA
•Track / Capture RWE to
sustain value argument
Phase I Phase II Phase III Filing Launch
TPP: Target Product Profile; TVP: Target Value Proposition
Simon Shohet, World Evidence and Pharma Pricing & Market Access Congress - London - February 21-23, 2017

8. 8
There are several channels for seeking early advice to
support evidence planning for reimbursement
Three mechanisms to get early advice: all offer
‘non-binding’ guidance
• National e.g. NICE + MHRA joint advice
• National level advice
• Face-to-face meeting with NICE and the Medicines and Healthcare products
Regulatory Agency.
• Regulatory and Health Technology Assessment advice in parallel, with reports from
both agencies
• Fees up to £50,000
• European Medicines Agency – Parallel Scientific
Advice
• Parallel regulatory and HTA advice procedure
• Started in 2010: choose which HTA bodies to invite
• Face-to-face meeting with participating bodies at the EMA offices
• Simultaneous feedback from regulators and HTAs on a pharmaceutical company’s
development plan
• Fees are invoiced at the end and depend on time and complexity
• EUNETHA – SEEDS: Shaping European Early Dialogues
• Multi HTA Consortium (14 agencies) led by HAS
• Project funded by European Commission
• 10 Pilot projects
AIFA, GBA, ZIN, TLV,
HAS, CADTH and
others also have
similar mechanisms
Simon Shohet, World Evidence and Pharma Pricing & Market Access Congress - London - February 21-23, 2017

9. Q & A