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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
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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
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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
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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
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Accelerated approval
• How to deal with the uncertainty of earlier approvals?
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71 1725
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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
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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)
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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
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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
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Thank you !!
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