Transcript AIFA spring conference - AIFA Agenzia Italiana del farmaco

Industry role in building clinical evidence
James Shannon, Head of Global Development
Giovanni Della Cioppa, Global Head of Methodology & Innovation –
Global Development Management Board
AIFA spring conference
30 March 2007
Agenda
 Pharma has a leading role in fighting disease…but
disease is not conquered yet
 The Pharma environment is challenging
 Health authorities and industry have a common goal
 The future will bring new demands
2 | AIFA spring conference| James Shannon| 30.03.2007 | | © Novartis March 2007
New pharmaceuticals contributed approximately 40%
to the increase of life expectancy since 1986
Cumulative Advantage in U.S. Life Expectancy at Birth
Years
2.5
Total Increase in Longevity
Increase in Longevity due to
Pharmaceuticals (est.)
2.0
2.0
1.8
1.7
1.5
1.5
1.4
1.2
1.1
0.9
1.0
0.7
0.8
0.6
0.5
0.4
0.2
0.0
0.1
0.1
0.0
1986
1987
1988
0.2
1989
0.4
0.3
1990
1991
Source: Frank Lichtenberg, NBER, EE.UU., 2003
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0.5
1992
0.6
0.7
0.5
0.6
0.6
0.7
1993
1994
1995
1996
1997
1998
0.7
0.8
1999
2000
Changing the practice of medicine
and outlook for patients
3 000
2 500
2 000
1 500
1 000
500
“Five years ago,
I was close to death. Now, I have a
grandson, Will, who is named for
Granny’s ‘will’ to live.”
– Ladonna Lopossa
Glivec patient
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0
CML deaths
Significant improvements, but prognosis still poor in
many cancers
Survival (%) during two time periods
by cancer site1
1974–1976
1992–1999
100
80
60
40
20
0
Prostate
Breast (Women)
Leukemia
Lung
Pancreas
5-year relative survival rates based on follow up of patients through 2000
Source: Surveillance, Epidemiology, and End Results Program, 1975-2000, Division of Cancer Control and
Population Sciences, National Cancer Institute, 2003.
1
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An aging population will drive a huge increase in
the burden of disease
Older population (age 60+) in major markets,
in % of total population
Drug usage in 2002 by population age group, in %
2010
2005
 100%
30
Germany
27
Spain
27
25
France
26
25
> 55 years
21
50
< 55 years
43
24
22
UK
Italy
23
21
Japan
23
21
US
US EXAMPLE
18
17
39
< 25 years
35
11
US
population
Rx drug
usage
Source: Mattson Jack Epidemiology database; 2002 US Census Bureau, Wall Street research, National Association of Chain Drug Stores
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Drug access programs for the less privileged
(Novartis example)
 Leprosy (free to WHO1):
Over four million patients treated since 2000
 Malaria/Coartem:
62 million treatments produced in 2006
 Tuberculosis (with WHO):
500 000 free treatments provided over five years
 Glivec2 Patient Assistance Program:
Free therapy to 20 000 people in 80 countries
 Novartis Institute for Tropical Diseases:
Singapore-based research initiative
1 World
Health Organization
in US
2 Gleevec
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Access
programs worth
USD 755 million
reached
33.6 million
patients in 2006
Agenda
 Pharma has a leading role in fighting disease…but
disease is not conquered yet
 The Pharma environment is challenging
 Health authorities and industry have a common goal
 The future will bring new demands
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Our environment is more difficult than ever
 Governments and payers increasingly aggressive in
managing costs:
• Price cuts, discounts, co-pays, formularies and other cost
containment measures
• Parallel imports
• Patent challenges
• Fast penetration of generics
 Pharmaceutical industry reputation is challenged
• Transparency
• Access to medicine
• Pricing
 R&D productivity has decreased
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More patients and trials are required
90
6000
80
5000
4237
70
3567
60
4000
3233
50
3000
40
30
1576
1321
2000
20
1000
10
30
30
36
60
68
82
1977-78
1981-84
1985-88
1989-92
1994-95
1998-2001
0
clinical trials
Source: SkyePharma, Parexel 2003/4
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patients
Average patients per NDA
Average clinical trials per NDA
5303
But productivity has declined
B. Booth & R. Zemmel. Nature Rev Drug Disc 2004
11 | AIFA spring conference| James Shannon| 30.03.2007 | | © Novartis March 2007
Agenda
 Pharma has a leading role in fighting disease…but
disease is not conquered yet
 The Pharma environment is challenging
 Health authorities and industry have a common goal
 The future will bring new demands
12 | AIFA spring conference| James Shannon| 30.03.2007 | | © Novartis March 2007
The common goal
Give patients
access to
innovative
treatments
WITH MAXIMAL EFFICACY
AND SAFETY
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Working with the FDA and EMEA from the customer
perspective
FDA
+
• Strong science-orientation
• Strong science-orientation
• Clear timelines for review
• Clear timelines for review
• Usually open dialogue with
• Strong central organization with
reviewers
_
EMEA
• Resources do not match current
needs
• In transition from conservative
model to Critical Path model
one voice for 27 member states
• Country-orientation vs medical
specialisation
• Heavy focus on cost,
sometimes independent of
benefit
• Country-specific safety related
constrains
• Country-specific
reimbursement negotiations
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Agenda
 Pharma has a leading role in fighting disease…but
disease is not conquered yet
 The Pharma environment is challenging
 Health authorities and industry have a common goal
 The future will bring new demands
16 | AIFA spring conference| James Shannon| 30.03.2007 | | © Novartis March 2007
Vision for the future of drug development is generally shared
by Health Authorities, Trade Associations, and Industry
Modernizing medical product development through innovation
Innovative
Medicines
Initiative
EMEA Road Map to 2010
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FDA Critical Path Initiative
Development vision 2015:
better, safer, faster through DELPhI1
Traditional Model
Approval
Preclinical
Ph.
I
Milestone
Ph.
IIa
Ph.
IIb
Milestone
Phase III
Milestone
Subm.
Milestone
from our current sequential,
multi-phase and milestone led
process to a more flexible,
adaptive model.
2015 Model
Modeling & Simulation
Confirmatory
Development
• DELPhI will minimize
Monitored
Release
Targeted
Milestone
Mile- Approval
stone
Full
Release
Full
Approval
Biomarkers
Continuous sharing of data with Health Authorities
1
development process at
Novartis fundamentally.
• DELPhI will create a shift
White Space
Exploratory
Development
• DELPhI will change the drug
Development excellence, productivity and innovation
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inconclusive results and help
to identify patients with the
best benefit-risk-ratio.
• DELPhI will speed up the
development process by
reducing the white space with
a strong focus on safety.
DELPhI
From vision to action
Vision
1.
Get the dose right
2.
All trials conclusive
3.
Minimal ‘white space’ and
rapid patient access
4.
Direct drug to patients –
direct data from patients
5.
Predict positive and negative
responders
6.
Predict safety issues to
minimize surprises
7.
Health Authorities embrace
DELPhI Vision & Objectives
8.
All Dev databases integrated
and easy to access
8 Objectives
>20 Major Projects
Sub-Projects / Activities
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Key drivers to transform the Development model
 Modeling and Simulation
 Rapid compound selection in man
 Biomarkers
 Innovative clinical trial designs
 Integrated safety assessment and risk management
 Technical R&D innovation
 Quality by design manufacturing
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Innovative trial designs are in implementation phase
 Adaptive trial design methodology workshops with
both the EMEA and the FDA
 Novartis has embarked on implementation of
adaptive designs in multiple registration programs
(5 on-going, up to 10 by the end of 2007)
• Adaptive designs: to adapt dose, target population,
sample size etc.
• Seamless adaptive designs: phase I/II, phase II/III, phase
III/IV
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Redefining end-points
Approval of anti-IgE in severe asthma
Exacerbations
FEV1
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The staged approval paradigm
Monitored
Release
Targeted
Approval
Full
Release
Full
Approval
 Staged approval is a two-step approval process paradigm.
 Its goal is to enable patients to have more rapid and controlled access
to targeted, innovative therapies based on qualified biomarkers while
enhancing learning about how best to use the medicine in the “real
world.”
 It differs from existing early approval mechanisms in that would be
applicable to targeted therapies for primary care indications as well as
more serious and life-threatening conditions.
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Why staged approval?
 Need to develop new approaches
• Long-term safety
• Less common adverse events:
To have a 95% chance of observing an adverse event
Expected rate
1 in
Number of patients to study on drug
1 000
3 000
1 in 10 000
30 000
1 in 100 000
300 000 -> uncertainty remains
 Narrowing of study population
 Targeted therapies dramatically enhance benefit/risk
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Experience to date
EU Conditional Approval
 Very limited experience; application of approach and definition of
“serious” indication not fully understood by industry
US Subpart H (Accelerated Approval)
 Widely applied to oncology and HIV/AIDs drugs, but some indication of
reluctance on the part of FDA to utilize this approach
Can these mechanisms be utilized for primary care
indications?
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Critical success factors to achieve staged approval
Advances in science must justify change in policy

Identification and qualification of biomarkers as surrogate
endpoints

Advancement of predictive safety

Advancement of pharmacovigilance methods
Staged approval must translate into a viable business
opportunity

Reimbursement, pricing, formulary acceptance must be adequate
to support the proposed approach
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