Bruno FLAMION, MD, PhDChair, Scientific Advice Working Party (SAWP) of the CHMP (EMA)Federal Agency for Medicinal and Health Products (FAMHP), BelgiumChair, Belgian Committee for Reimbursement of Medicines (CTG-CRM)Professor of Physiology & Pharmacology, FUNDP Namur, Belgium

How to accelerate approval of innovative drugs

Created 26 January 1995

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Disclaimer

My presentation might not be the view of the of the CHMP/SAWP, the EMA, or the FAMHP. My presentation is a personal viewpoint and binds in no way the organisations mentioned above.I have no financial interest to declare.

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Acknowledgement

Prof. Hans-Georg Eichler, EMA

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The drug development productivity gap

Global sales

Global R&D expenditure

Development times

Global NME output

From: CMR International & IMS Health, 2008

Accelerated approval

• Is early access to the market the most appropriate solution to the productivity gap ?

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Are regulatory agencies raising the entry bar?

Yes

Nature Rev Drug Discov May 2010

29/48 (60%) New Active Substances approved by CHMP in 2009

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The regulator’s dilemma

Nature Rev Drug Discov Dec 2008

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Eichler HG, Pignatti F, Flamion B, Leufkens H, Breckenridge A.Nature Rev Drug Discov 2008

The regulator’s dilemma

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Time

Timing of market authorisation?

Level of knowledge

Accelerated approval

• Accelerating approval of innovative drugs is a risky business for regulators

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Evolution of Remicade (infliximab) at EMA

1999 2000 2001 2002 2003 2004 2005 2006

RA: signs and symptoms

Fistulizing CD maintenance

Ankylosing Spondylitis

Luminal CD maintenance

Early RA

Psoriatic Arthritis

Moderate/Severe Psoriasis

Ulcerative Colitis

RA:joint damage

Crohn’s Disease

RA: physical function

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Dinv lettertransaminases

CHF DDL

SP commitment to CD and RA registry

German “death scare”

TB education

DDL Lymphoma

FDA panel Lymphoma

DDL Hepatotoxicity

HepatotoxicityPSUR3 pancytopenia listeriosis

1998 1999 2000 2001 2002 2003 2004 2006

TB/infectionsalert card

PSUR4 interstitial pneumonitis/fibrosis

PSUR 6 & 7 vasculitis

PSUR 8 agranulocytosis,pancreatitis

Severe infections

serum sickness, pericardial effusion

Malignancies

Delayed Hypersensitivity

PSUR 9 heart failure

T24 stopped

Alcoholic Hepatitis study stopped

PSUR 5 myelitis, anemia, hepato cellular damage

2005

CD: 2nd to 3rd line therapy

Label ChangeLabel Change

DDL or other event DDL or other event

FU commitment FU commitment

Dinv Letter hematological AE

TB DDL

General DDL

Pneumonia

Evolution of Remicade (EU): Safety

Evolution of Acomplia (rimonabant)

Selective CB1 antagonist

Approved April 2006

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Enabling rapid access to market

Legal instrument in place since 2006:Conditional Marketing Authorisation

Several requirements, including: “...The benefit/risk balance is positive.”“...Benefits to public health of the immediate availability outweigh the risks inherent in the fact that additional data are still required.“

Illustrates the growing need for post-marketing benefit-risk assessment

Accelerated approval

• How to deal with the uncertainty of earlier approvals?

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201

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136

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0 50 100 150 200 250 300 350 400

2000200120022003200420052006200720082009

Scientific Advice Protocol Assistance

* Protocol Assistance = Scientific Advice for Orphan Medicinal Products

Scientific Advice (SA) and Protocol Assistance

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Eur J Clin Pharmacol2010 Jan; 66(1): 39-48

Benefits of SA

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Compliance with SA (vs no advice) gives an odds ratio of 14.71 (1.95 – 111.15) for a successful approval

Scientific Advice on future studies required for

qualification purposesCHMP Public Opinion on

the QualificationOR

Qualification of novel methodologies

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Example of a successful BMQ process

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Example of a successful BMQ process

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EMA and precompetitive research

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• Qualification of novel methodologies

• Early dialog between industry with regulators: e.g., non-binding “Briefing Meetings” on pharmacogenomics, personalised medicines, drug-diagnostic combinations, etc.

• EMA participation in Public-Private-Partnerships (e.g. IMI)

EMA participation in IMI first call projects

EMA role/participation

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“EMEA’s proposal that it will undertake outcomes research using the vast data pool it has available is encouraging…”

From: The IMI Research Agenda 2009

EMA could also mine and share data

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Another type of incentive

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Finally, a critical question...

• Relative efficacy• Relative effectiveness• What is the role of national pricing and reimbursement

committees?• What is the role of HTA bodies?• What is the role of EMA?

(EMA RoadMap to 2015) “There is no reason why the EMA and the HTA bodies should take a different approach to the assessment of net health benefit (benefits minus risks) since the ultimate objective should be to achieve integrated medicine development satisfying the various needs.”

How to measure the level of innovation

Conclusions - 1

• Accelerating approval of innovative drugs is a risky business for regulators

• What we need is: earlier, more focused knowledge more understanding of the mechanism of action personalised medicines drug-device & drug-diagnostics developments

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Conclusions - 2

• Companies and consortia are advised to consider early dialogs with regulatory bodies (informal contacts, Briefing Meetings, Qualification processes, Scientific Advices…)

• What incentive/benefit for innovative drugs ?

• (Unavoidable) How to measure the level of innovation ?

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In the end, regulatory decisions must be appropriate, predictable and consistent

Thank you !!

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