what are the obstacles in analgesic development? · 2012-04-22 · non-narcotic analgesics narcotic...
TRANSCRIPT
Kenneth I Kaitin, Ph.D. Director and Research Professor
Tufts Center for the Study of Drug Development
ACTION Workshop – FDA White Oaks Campus Silver Spring, MD, June 15, 2011
Current R&D Challenges
What are the Obstacles in Analgesic Development?
Current Realities for Pharmaceutical Developers
Patents on many high revenue products are expiring
Marketplace is highly competitive and reimbursement environment is increasingly restrictive
Public support is low
Regulatory hurdles are increasing
Pharmaceutical R&D remains a long, risky, and expensive process
$3.6
$4.9
$5.3
$5.9
$6.1
$6.8
$8.1
$8.1
$9.2
$9.4
BMS
Lilly
AstraZeneca
Sanofi Aventis
GSK
J&J
Novartis
Merck
Roche
Pfizer
Billions of US$
Top Ten R&D Spenders for 2010
Sources: FierceBiotech, 3/8/11
New Drug Approvals Are Not Keeping Pace with Rising R&D Spending
0
13
26
39
52
0
15
30
45
60
1963 1968 1973 1978 1983 1988 1993 1998 2003 2008
R&
D E
xp
en
ditu
res
(B
illion
s o
f 20
08
$) N
ew
Dru
g A
pp
rov
als
R&D Expenditures
New Drug Approvals
* Trend line is 3-year moving average; R&D expenditure adjusted for inflation
Source: Kaitin, Clin Pharmacol Ther, 2010;87:356-361
http://www.nature.com/clpt/journal/v87/n3/full/clpt2009293a.html
Bringing a New Analgesic to Market: Development Metrics
0 11
AIDS Antivirals
Anesthetic/Analgesic
Antiinfective*
Gastrointestinal
Immunologic
Cardiovascular
Endocrine
Antineoplastic
CNS
4.6
5.3
5.4
5.8
6.4
6.5
6.5
6.9
8.1
0.5
0.8
1.2
2.4
1.0
1.3
1.2
0.7
1.9
Years
Clinical Phase Approval Phase
10.0
7.7
7.8
8.2
6.6
5.1
6.1
7.4
7.6
* excludes AIDS antivirals
Clinical and Approval Times Vary Across Therapeutic Classes, 2005-09
Source: Kaitin & DiMasi, Clin Pharmacol Ther, 2011;89:183-188
Clinical Development Times in Three Decades
Source: Kaitin & DiMasi, Clin Pharmacol Ther, 2011;89:183-188
0
10
2.3
6.2
4.2
7.4
6.1
7.9
3.9
6.6
5.4
7.8
5.8
7.0
5.0 4.9
6.6
7.4
5.3
8.6
Years
1980-1989
1990-1999
2000-2009
* excludes AIDS antivirals
Overall Clinical Approval Success Rate for NCEs has Dropped to 16%
0 27
CNS
Cardiovascular
GI/Metabolism
Arthritis and Pain*
Oncology/Immunology
Musculoskeletal
Sys. Antiinfective
8.2%
8.7%
9.4%
19.4%
20.4%
23.9%
17%
Clinical Approval Success Rate
Source: DiMasi et al, Clin Pharmacol Ther, 2010;87:272-277
* Arthritis and Pain figure based on Kola and Landis, Nature Rev Drug Disc, 2004;3:711-715
Long Development Times + Low Success Rates = High R&D Costs
0
1500
Non-Clinical Clinical Total Costs
615 626
1,241
439
879
1,318
Millio
ns o
f 2005 D
ollars
Biotech Pharma (Time Adjusted)
Source: DiMasi & Grabowski, Managerial Decision Econ, 2007;28:469-479
Time Adjusted Capitalized Clinical Costs by Therapeutic Area
$604
$741 $750$792
$849
0
1000
Mil
lio
ns
of
20
05
Do
lla
rs
Anesth/Analg Cardiovascular All Antiinfective CNS
Source: DiMasi et al, Drug Info J, 2004;38:211-223
$20,457
$17,094 $16,653
$14,163
$12,500 $11,784
$10,850 $10,213 $9,835 $9,547
$8,948 $8,056
$6,341
$4,265
$0
$5,000
$10,000
$15,000
$20,000
$25,000
Clinical Trial Costs per Patient (all phases), 2007-2009
Source: TTC, llc; Parexel Statistical Sourcebook 2010-11
Approved NMEs by Therapeutic Class in Three Decades
Source: Kaitin & DiMasi, Clin Pharmacol Ther, 2011;89:183-188
0
80
4
25
51
11
52
20
7 10
3 3
23
35
41 38
74
35
25
9 10
18
10
20
30
47 49
27 26
11 12
7
Nu
mb
er
of
Ap
pro
vals
1980-1989
1990-1999
2000-2009
* excludes AIDS antivirals
Market Size
Competitive Landscape
Exploitable Science
Portfolio Risk
What Factors Influence a Company’s Decision to Invest in a Therapeutic Area
Source: Tufts CSDD, 2011
Top 15 Therapy Classes in 2009 Global Pharmaceutical Sales
$10.8 bil
$11.2 bil
$11.2 bil
$13.0 bil
$13.8 bil
$14.6 bil
$18.0 bil
$19.4 bil
$23.2 bil
$25.2 bil
$29.6 bil
$30.4 bil
$33.6 bil
$35.3 bil
$52.4 bil
Erythropoietins
Non-Narcotic Analgesics
Narcotic Analgesics
Anti-Epileptics
HIV Antivirals
Platelet Aggr. Inhibitors
Autoimmune Agents
Antidepressants
Antipsychotics
Angiotensin-II Antag.
Anti-Ulcerants
Antidiabetics
Respiratory Agents
Lipid Regulators
Oncologics
Source: IMS Health Midas, December 2009; Parexel Statistical Sourcebook 2010-11
2.7% of Global
Market
Source: Kissin I. The Development of New Analgesics Over the Past 50 Years: A Lack of
Real Breakthrough Drugs. Anesthesia & Analgesia 2010; 110(3): 780-789; Tufts CSDD
Development Classification of New Analgesics
Category N
Incremental improvement on an existing
drug mechanism
41
Novel selective mechanism of an existing
drug
3
Completely novel mechanism of action 1
Total 45
Portfolio Decision-Making Grid
— — Anesth/Analgesic
Oncology
—
—
—
— CNS
— Cardiovascular
— — Infectious Disease
Market Size Competitive
Landscape Portfolio Risk
Exploitable
Science
—
—
—
Source: Tufts CSDD, 2011
Oncology 34%
Central Nervous System 15%
Antiinfectives 11%
Cardiovascular 7%
Diabetes 7%
Respiratory 7%
Pain and Inflammation 6%
Gastrointestinal 5%
Blood 4%
Dermatology 3%
Compounds in Development in Top 10 Areas: Oncology Leads
Source: R&D Directions; Parexel Statistical Sourcebook 2010/2011
Development Challenges for Analgesics
Multiple etiologies
Poor understanding of pain mechanisms
Patient response variability: poor understanding why
Clinical trial challenges:
Poor overall responsiveness to chronic treatment
High placebo response
Poor patient reporting
Insensitive and imprecise clinical endpoints
Chronic use products often with abuse potential
Post-approval safety and risk management demands
Highly competitive market and strong generic penetration
Source: Tufts CSDD, 2011
A FIPNet Model for Drug Development: The Emergence of Innovation Nodes
Phase IV
Studies Approval
Late Stage
Development
Early Stage
Development
Discovery
Preclinical
Research
Pre-Discovery
Large Pharma
Academia
Biotechs/
Small Pharma
CROs/Other
Partners
Basic Research Translational Medicine
Execution, Monitoring, Analysis
Innovation, Partnerships
Coordination, Management Execution, Monitoring, Analysis
Large Scale Clinical Trials
Data Analysis
Medical Writing
Regulatory Approval
Source: Kaitin, Clin Pharmacol Ther, 2010;87:356-361
http://www.nature.com/clpt/journal/v87/n3/full/clpt2009293a.html
Oncology
AD Peds
RA
Diabetes
Source: Tufts CSDD, 2011
How Innovation Nodes Will Work
Tufts Center for the Study of Drug Development Tufts University, Boston, Massachusetts, USA
Kenneth I Kaitin, Ph.D. Director and Research Professor
Tufts University School of Medicine
Website http://csdd.tufts.edu
Email [email protected]