Transcript Medicines- from Trial to Market View from Pharma

PROCUREMENT &
DISTRIBUTION INTEREST
GROUP
Autumn Symposium 2007
http://www.pdig.org.uk/
Medicines- from
Trial to Market
View from
Pharma
Dr David Gillen
Medical Director
Pfizer UK
Coventry November 8th 2007
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The second Gap in Translation –
Cooksey 2006
3
The Future Challenge: Demographics!
As the population ages healthcare costs grow rapidly
Growing burden of age
Healthcare cost relative to
50 - 64 age group
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US
Canada
10
UK
Australia
8
Japan
Germany
6
Sweden
Spain
4
2
0
50-64
65-69
70-74
Age Group
75-79
80+
Older people consume more healthcare than younger people do
PricewaterhouseCoopers LLP
Eye-4-Pharma,
Sources: Laurence Kotlikoff and Christian Hagist, “Who’s Going Broke?” National Bureau of Economic Research,
Working
Paper No. 11833, December 2005, p.25; World Factbook, 2006; OECD Health Data 2006; IMS Sales Data 2005.]
March 2007
Slide 6
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Medicines Extend Quantity and Quality of Lives
Drop In Death Rates For Diseases 1965-1996
Disease
Atherosclerosis
Ulcer of Stomach
and Duodenum
Ischemic
Heart Disease
Emphysema
Hypertension
Treatment
74%
Statins, ACE inhibitors, beta blockers, nitrates
72%
H2 blockers, proton pump inhibitors
62%
ACE inhibitors, beta blockers, nitrates
57%
Anti-Inflammatories, bronchodilators
Anti-Hypertensives,
diuretics
0%
21%
20%
40%
60%
80%
DEATH RATE
Source: Lasker/Funding First
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Yet…New Product Development Is a
Risky and Expensive Proposition
Compound Success
Compound
Success
Rates by Stage
Rates by Stage
Years
00
Discovery
(2–10 Years)
Phase I
20–80 Healthy Volunteers Used to
Determine Safety and Dosage
22
4
66
88
Phase III
10
10
1,000–5,000 Patient Volunteers
Used to Monitor Adverse
Reactions to Long-Term Use
12
12
Additional PostMarketing Testing
Preclinical Testing
Laboratory and
Animal Testing
14
14
16
16
Phase II
100–300 Patient Volunteers
Used to Look for Efficacy
and Side Effects
FDA Review Approval
5,000–10,000
5,000–10,000
Screened
Screened
250
250
Enter
Enter
Preclinical
Preclinical
Testing
Testing
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Enter
Clinical Testing
1
Approved by the FDA
Net Cost: £400 Million
Invested Over 15 Years
Sources: 1) Increased Length and Complexity of the Research and Development Process. Chapter 1 in: PhRMA Pharmaceutical
Industry Profile 2003. 2) DiMasi, JA, Hansen, RW, Grabowski, HG. The Price of Innovation: new estimates of drug development
costs. Journal of Health Economics. 2003; 22:151-185.
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2.a, 2.b
So much for so little…
Global R&D Spending ($ in MN)
NME and New Biologics Approved
60
R&D Spending ($ in MN)
45,000
50
40,000
35,000
40
30,000
25,000
30
20,000
20
15,000
10,000
10
5,000
0
No. of NME, BLA Approvals
50,000
0
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004* 2005* 2006*
Source: FDA/CDER Data, PhRMA data, Pw C analysis
* includes Biologics
Even allowing for inflation, the industry is investing twice as
much in R&D as it was a decade ago to produce two-fifths of
the new medicines it then produced.
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So what is the reality of this translation
and how can we improve it?
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For patients, standards are still held back by the slow
uptake of medicines
Share of products grouped by year of first sales in total non-generic pharmaceutical
sales (%, 2006)
Year of first sales
100%
Post-2002
1998-2001
Pre-1998
18
17
33
33
32
41
47
49
51
Spain
US
23
36
20
Germany France
NOTE: IMS data includes parallel trade for the UK, but excludes it for all other countries
See appendix for additional analyses on uptake
Source: IMS Health, team analysis
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16
28
24
56
60
UK
Italy
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Relative survival in All Malignancies in
Europe- Lancet Oncology 2007
…UK relative survival below the
Mean Eurocare Region 47 % men
55 % women….
Lancet Oncology 2007 8 784-796
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Sunitinib- An Oral Multitargeted Tyrosine
Kinase Inhibitor
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Sunitinib- An Example of the challenge in
the UK
Professor Bob Hawkins from Christie hospital said:
"We would like [Sutent] to be available for every patient.
"We would still encourage patients to go into the
trials of new treatments
because that's the only way we're going to make
progress on drugs like
Sutent.
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Compassionate Use
Must Adhere to
Regulatory
Requirements
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Use of unlicensed medications

An unlicensed relevant medicinal product may
only be supplied to third parties if it is:
 supplied in response to a bona fide unsolicited
written request;
 formulated in accordance with the requirement
of a doctor or dentist registered in the UK;
 for use by their individual patients on their
direct personal responsibility;
 supplied under specific conditions
MHRA Guidance Note 14 2006
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Phase III b study for Sunitinib
Renal Cancer UK Globally highest recruiter
To be enrolled
n = 5,000
Enrolled as of 1 May ‘07
n = 4,470
Data available
n = 2,341
ITT population
Safety
Treatment duration
Response rate
With potential FU >6 mo
(incl. PD / )
n = 2,125
PFS
OS
No prior cytokines:
n = 285
Prior cytokines:
n = 1,840
Subgroups
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Sunitinib- NICE review due 2009
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Oncology: A Particular Challenge for HTA
1.
HTA is limited in its application to end stage oncology in large
part because of the nature of these conditions.
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
2.
3.
QALY assessments do not capture the true value of therapy and
fail to weight survival gains relative to life expectancy.
Conditions are rare so share many of the limitations presented by
the application of HTA to orphan products, data scarcity and
uncertainty, necessarily high costs plus associated high budget
impact.
Cancer treatment evolves incrementally. This has produced
significant improvements in survival beyond what is seen in
the Phase III trials of existing products which can not
efficiently be achieved through formal trial programs. Denial
of access obviously stifles this evolution
The UK now has one of the lowest uptakes of new oncology
products in Europe.
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Moving forwards- Is there a different way?

Drug Development and the opportunity of Inline Real World testing

Risk Sharing

HTA reform
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The future - integrated healthcare?

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Mainly biologically based
Based on clinically validated
target(s)
Targeted to specific disease
populations
Disease modifying
Compliance and persistence
monitored and ensured
Prophylactic treatment of
susceptible
Supported by a network of services
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Drug Development and the opportunity of
In- line Real World testing
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Risk Sharing : Velcade (Bortezomib)

Britain's NICE (on Wednesday 24th Oct) published final
guidance to the National Health Service (NHS) on the funding
of Janssen-Cilag's Velcade (bortezomib) in multiple
myeloma, including the introduction of a novel risk-sharing
scheme.
In a statement, the cost-effectiveness watchdog said:
"The guidance confirms the response-rebate scheme which will
allow patients at first relapse who show a full or partial
response to bortezomib to carry on with the treatment, fully
funded by the NHS, and patients who show no or minimal
response to be taken off the drug and the drug costs
refunded by the drug's manufacturer."
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Pfizer principles of HTA (1)

1. The views of physicians and patients are an
essential component in assessing the value of
medicines and healthcare decision-making

HTA should formally incorporate physician and
patient views

Guidance should recognise that patient preferences
and responses to medicines vary and thus permit
physicians to prescribe contrary to guidance without
undue burden to justify their decision
Alzheimers –
limit treatment
to moderate
patients
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Pfizer Principles of HTA (2)
HTA should reflect the full value of medicines to UK society
 HTA should focus on cost and benefits of new
medicines to society rather than the NHS alone
 HTA needs to recognise that the value of medicines
takes many forms and incorporates all these
dimensions rather than focus solely on clinical
outcomes
 The development of new healthcare technology
requires that HTA appraisals recognise and reward
incremental innovation
Alzheimers – Residential
care costs borne by
patients and their
families were excluded
in the Alzheimer’s
appraisal
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Pfizer Principles of HTA (3)
HTA, especially close to launch, requires a pragmatic
approach to assessing evidence and developing
guidance

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The real value of a medicine will only be confirmed
after launch following sufficient and appropriate use
in a real world setting
Uncertainty about treatment effect and economics
will always exist. HTA needs to ensure that risk
averse decision making does not stifle innovation
and deny patients access to medicines
Single Technology
Appraisals – The need
for pragmatism is not
explicitly stated in
guidance to evidence
review groups
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Pfizer Principles of HTA (4)

4. The reliability of economic analyses need to be
explicitly considered within the decision making
process
 Measurement and valuation methods are evolving but
remain imprecise
 Models are only as good as the underlying structure
and assumptions
 Models often contain a high degree of uncertainty
 Models can be relatively unstable – a small change in
one or more parameters can lead to very different
results and conclusions
The Alzheimer’s Disease economic model - assumptions and
parameter estimates that do not reflect current practice, resource use
and costs.
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Pfizer Principles of HTA (5)
.
HTA must include an open, transparent decision making
process that involve all stakeholders, covers all health
technologies, makes full balanced use of all evidence,
contains a fair appeal process, and makes decisions in
a timely manner.
Manufacturers are not represented at the appraisal committee hearing.
The appeal process focuses on whether process has been followed
NICE do not engage with manufacturers during drug development
process to discuss data requirements.
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Pfizer Position on HTA

The UK government should ensure that it receives
value for money from the medicines it procures
through the NHS. Current methods for assessing
value for money through Health Technology
Assessment (HTA) are limited.

HTA increasingly undermines patients’ access to
innovative new treatments

HTA leads to uncertainty in the drug development
process

HTA risks undermining the future development and
availability of new medicines.
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Key issues during the transition from Trials to
licensed products
The pharmaceutical industry needs
to be a partner with not an
adversary of the NHS and we must
work with all stakeholders to allow
the next generation of Innovative
Medicines to be available …..
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“ We try never to forget that medicine is for the
people. It is not for the profits. The profits
follow, and if we remembered that, they have
never failed to appear. The better we
remembered that, the larger they have been…”
George Merck- Founder of MSD
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