Regulatory and Reimbursement Harmonization An Industry Perspective

Adrian Griffin | April 2016

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One Global Development Plan Many geographies, More Stakeholders

Discovery

3 yrs

Early Development

2 yrs

Phase II

2 yrs

Phase III

3 yrs

Regulatory review

1-2yrs

Launch

Need to know evidence requirements 4-7 yrs before launch

Initial

Plan

Evidence

Plan

‘Locked’

Clinical

Use

Planning the Evidence -

Predicting the future

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Need for Regulatory and HTA Agencies to be Aligned

Focus of HTAi Policy Forum, 2011

International Journal of Technology

Assessment in Health Care, 27:3 (2011),

Page 1 of 8.

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Different Focus, Different Decisions Both driving for better outcomes for patients

Regulation HTA Coverage

Role Give market

authorisation

Support for clinical and

coverage decisions

Decide on coverage or

reimbursement

Decision Do the clinical

benefits for patients

outweigh the risks?

[HTA supports

decisions, often taking

into account clinical,

financial & other

dimensions]

Are the expected

health benefits useful

and affordable?

Evidence Efficacy and safety from

trials; post launch

surveillance

Effectiveness, cost

effectiveness and

opportunity costs from

trials, other studies and

modelling

As for HTA; conditional

coverage may be used

to improve evidence

base for re-appraisal

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Regulatory-HTA Interactions have been Increasing

Timing

• Pre-competitive

• During Development

– Pre-Phase II / III

• Pre-Market / launch

Type of Interaction

• Disease Specific

– Evidence Guidance Documents

• Green Park Collaborative

• Early Scientific Advice

– Product specific advice

– HTA, Multi-HTA, Parallel Reg-HTA

• Parallel reviews

– Regulatory and reimbursement

• Canada, Australia, US

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• Regulator, patient, clinicians call for ‘early

access’

– FDA: Breakthrough therapies

– EMA: PRIME

• Regulators discussing longitudinal

approach to approval

– “Adaptive Licensing”

Now Medicines Adaptive Pathways to

Patients (MAPPs)

• How will HTA & Reimbursement adapt?

– Existing approach to value assessment

needs to evolve

New Challenges for Stakeholders

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Ibrutinib versus Ofatumumab in previously treated CLL:

Byrd et al, NEJM, July 2014

The Challenges are here now

Crossover bias

Ofatumumab as single agent CD20 immunotherapy in

fludarabine-refractory CLL: Wierda et al, JCO, April 2010

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Ongoing Initiatives

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Ongoing Initiatives (2)

To show how Real World

Evidence (RWE) can be adopted

in to medicine development &

decision making, and provide the

tools to achieve it

https://www.imi-getreal.eu/

An enabling platform to

coordinate MAPPs activities.

Supporting evidence generation,

designing the MAPPs pathway,

decision-making & sustainability

http://adaptsmart.eu/

Both are multi-stakeholder, including regulators, HTA agencies, patient

organisations, academics and industry

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Countries can find ways to deliver access, whilst managing their uncertainty

Scheme type

Rebate for early non-responders

Capped treatment duration

Treatment duration linked rebate

Response scheme

Initiation period costs

Population level cap

Range of Managed

Entry Agreement

Archetypes in use in

Europe, for One Drug in

one Disease

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Challenges

• Regulators are Decision-Makers – Able to change their decision-making paradigm

• HTA-agencies provide information & recommendations – Third parties then make Reimbursement decisions

• What flexibility do HTA-agencies have to navigate the reimbursement access

model? – Will a new model be required in the new regulatory environment

• Industry needs to address Regulators, HTAs, Clinicians and Patients