Access and Benefi t Sharing - Key Points for Policy-Makers Sarah A. Laird - ABS Initiative
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Access and Benefit Sharing
Key Points for Policy-Makers
THE PHARMACEUTICAL INDUSTRY
Sarah A. Laird
November 2015
SUMMARY OF KEY POINTS
MARKETS, COMPANIES AND PRODUCTS NATURAL PRODUCTS RESEARCH
Revenues have increased steadily over the last 30 years, but in Although support for natural products research in large
recent years growth has slowed in developed country markets companies has declined, the contribution of natural products to
while in ‘pharmerging’ markets it has increased. the development of new drugs continues, and between 1981-
The world’s largest pharmaceutical companies are located in 2013 an average of 31% of all new drugs annually were natural
developed countries. Their earnings make them some of the products.
wealthiest companies in the world. Natural products research has undergone dramatic changes
The pharmaceutical industry has undergone significant in the last 50 years, with significant implications for the speed,
consolidation over the last 30 years in order to increase growth scale and focus of R&D, and the design of effective ABS
and acquire new technologies, expertise and novel drug measures.
candidates. Traditional knowledge, once the primary lead for the discovery of
Many of the industry’s top-selling drugs have gone off-patent, new medicines, is no longer a significant part of industry R&D.
resulting in reduced revenues in recent years. Patent expiries
on small molecule products will reduce brand spending in INDUSTRY AND ABS
developed markets by $113 billion through 2017. The pharmaceutical industry is more aware of the Convention
A top-selling pharmaceutical product can now generate more on Biological Diversity than many other sectors, although this is
than $5 billion in sales a year. more the case with large companies than with small. However,
Specific disease areas and products differ significantly between many concerns persist within industry about legal certainty and
developed and pharmerging markets. the need for new measures drafted to implement the Nagoya
Protocol to reflect the scientific, business and legal realities of
natural products research today.
TRENDS IN RESEARCH AND DEVELOPMENT
Spending on R&D has increased over the last few decades but
productivity has gone down. The number of new drugs coming
on the market each year has held roughly steady or declined
since 1981.
Government contributions to pharmaceutical R&D remain high
across the globe. In the US, for example, government funding
contributed to 48% of all drugs approved by the FDA and 65%
of drugs that received priority review between 1988-2005.
Drug discovery, including that on natural products, is
increasingly done in smaller start-up companies, academia and
government laboratories, with large companies undertaking
development and marketing.
2
MARKETS, COMPANIES AND PRODUCTS
Global growth rates
1 200
7%
37% NORTH AMERICA 1 000 13%
Revenues have LATIN AMERICA 800
7%
increased steadily
USD billion
600 2%
over the last 30 years, 400
but in recent years $989 billion of 200
2%
growth has slowed 29% global spending 0
in developed country
ASIA / on medicines 2008 2012 2017 (F) CAGR*
markets while in AUSTRALIA
2012-2017
‘pharmerging’ markets Pharmerging markets Between 2012 and
it has increased. Other emerging markets
2017, Pharmerging
markets have growth
rates far higher than
4% AFRICA / MIDDLE EAST Other developed markets
in mature markets.
24% Top 8 mature markets
EUROPE *CAGR (Compound Annual Growth Rate)
EUROPE
The world’s largest pharmaceutical companies are located in developed 2013 R&D
countries. Their earnings make them some of the wealthiest companies RANK COMPANY COUNTRY
2013 SALES
(USD million)
SPENDING
2013 TOP-SELLING DRUGS
(USD million)
(USD million)
in the world.
Gleevec ($4,693) Diovan
1 $46,017 $9,360
($3,524) Lucentis ($2,383)
NORTH AMERICA
2013 R&D
Rituxan ($7,503) Avastin
2013 SALES 2013 TOP-SELLING DRUGS 3 $39,143 $8,294
RANK COMPANY COUNTRY SPENDING ($6,751) Herceptin ($6,562)
(USD million) (USD million)
(USD million)
Lantus ($7,592) Plavix
4 $37,701 $6,117
Lyrica (4,595) Prevnar ($2,460) Lovenox ($2,262)
2 $45,011 $6,254
($3,974) Enbrel ($3,774)
Top Companies
Seretide / Advair ($8,251)
Januvia ($4,004) Zetia 6 $33,055 $5,041 Pediarix ($1,349)
5 $37,519 $7,123
($2,658) Remicade ($2,271) Avodart ($1,341)
Remicade ($5,334) Zytiga Crestor ($5,622) Nexium
7 $26,475 $5,810 8 $24,523 $4,269
($1,698) Prezista ($1,673) ($3,872) Symbicort ($3,483)
Cymbalta ($5,084) Alimta
9 $20,119 $5,316 13 $15,594 $2,710 Kogenate ($1,597)
($2,703) Humalog ($2,611)
Humira ($10,659) AndroGel
10 $18,790 $2,831 14 $14,886 $2,090 NovoRapid ($3,001)
($1,035) Kaletra ($962)
11 $18,192 $3,941 Enbrel ($4,551) 15 $14,468 $3,247 Spiriva ($4,719)
17 $12,306 $3,715 Reyataz ($1,551) ASIA / AUSTRALIA
2013 R&D
2013 SALES 2013 TOP-SELLING DRUGS
RANK COMPANY COUNTRY SPENDING
18 $10,804 $2,056 Atripla ($3,648) (USD million) (USD million)
(USD million)
AFRICA / MIDDLE EAST 16 $13,591 $3,352 Biopress ($1,256)
2013 R&D
2013 SALES 2013 TOP-SELLING DRUGS
RANK COMPANY COUNTRY SPENDING
(USD million)
(USD million)
(USD million) 19 $10,431 $2,132 Prograf ($1,755)
12 $17,563 $1,422 Copaxone ($4,328) 20 $10,268 $1,926 Benicar ($2,116)
3
The pharmaceutical industry has undergone significant consolidation over Many of the industry’s top-selling drugs have gone
the last 30 years in order to increase growth and acquire new technologies, off-patent, resulting in reduced revenues in recent
expertise and novel drug candidates. years. Patent expiries on small molecule products
will reduce brand spending in developed markets by
$113 billion through 2017.
1980
No. Companies: (including Amgen and Johnson and Johnson) 33
Merck Hoffman Hoescht Roussel Squibb Sandoz Glaxo Pfizer
Marion Merril Developed markets patent expiry 2008-2017
Schering-Plough Genentech Dow Bristol Myers Ciba-Geigy Wellcome Parke-Davis
60
Organon Rhone Poulenc DuPont Pharma Burroughs Warner Lambert
$149 billion $123 billion
Smith Kline & 40 Pre-expiry spending
Sanofi Merck DuPont French Monsanto
SPENDING US BILLION
Synthelabo Beecham Searle 20
21.0 22.3 26.9 28.4 50.3 19.1 31.7 28.8 20.3 22.6
Upjohn 0
-18.5 -15.3 -21.5 -22.6 -43.6 -32.1 -17.2 -26.2 -22.5 -15.9
Pharmacia -20
Consolidation has been a continuing process
A H Robbins -40 -$121 billion -$113 billion
Lower brand spending
Lederle (AHP)
-60
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
Wyeth
Protection US Japan UK France Germany
expiry year
H-LaRoche Hoescht Squibb Sandoz SmithKline Pfizer Plavix Nu Lotan Lipitor Tahor Seroquel
Syntex Beecham 2012 Seroquel Myslee Amias Singulair Atacand
Sanofi/ Singulair Preminent Seroquel Pariet Atacand Plus
Genentech Synthelabo Bristol Meyers Ciba-Geigy Warner Lambert Actos Haigou Aricept® Ixprim Sortis
Lexapro Seroquel Singulair Aprovel Aricept
RhonePoulenc & Monsanto Searle Diovan
Fisons Diovan HCT®
Marion Merril Pharmacia Geodon
Dow Upjohn Viagra
Boniva
Lederle (AHP) Oxycontin® Diovan Viagra Seretide Viani
2013 Aciphex Plavix Xeloda Coaprovel Zometa
Wyeth Zameta Livalo Xeloda Atmadisk
Xeloda Elplat Micardis Coaprovel
Opana ER Viagra Viagra
Asacol
Hoescht Roussel Bristol-Meyers SmithKline Pfizer Nexium® Axura
Squibb Beecham Prograf Abilify Seroplex
2014 Cymbalta Glivec Cipralex Abilify Risperdal Consta
Sanofi/ Burroughs- Pharmacia Cerebrex Abilify Risperdal Consta Ebixa Biopress Plus
Synthelabo Wellcome Symbicort Risperdal
Lunesta Consta LP
RhonePoulenc & Glaxo Lederle(AHP)
Fisons Restasis
Evista
Sandostatin LAR
Wyeth
Actonel
Abilify Zyprexa Spiriva Alimta Spiriva
2015 Copaxone Adoair Cymbalta Spiriva Copaxone
Merck Hoffman Aventis GlaxoSmith Kline Wyeth Gleevec Alimta Alimta Copaxone Alimta
LaRoche Namenda Spiriva Protelos Cymbalta
Sanofi/ Provigil Symbicort Cymbalta
Schering-Plough Synthelabo Pfizer Combivent
Zyvox
Prezista
Avodart
Merck Roche Sanofi-Aventis Bristol-Meyers Novartis Glaxo Pfizer
Squibb SmithKline Crestor Blopress Glivec Glivec Glivec
2016
9
Benicar Baraclude Vfend Cancidas Zyvoxid
2010 Benicar HCT
Vfend Vfend
Cubicin
4
A top-selling pharmaceutical
product can now generate Specific disease areas and products differ
more than $5 billion in sales significantly between developed and
a year. pharmerging markets.
Top ten global products 2013 Spending by therapy area (projected for 2017)
2013 sales (USD million)
DEVELOPED MARKETS Projected sales in 2017 PHARMERGING MARKETS Projected sales in 2017
(USD billion) (USD billion)
1 $9,851
Oncology $74-84 billion Pain $22-25 billion
Diabetes $34-39 billion Other CNS Drugs $20-23 billion
2 $9,213 Anti-TNFs $32-37 billion Antibiotics $18-21 billion
Pain $31-36 billion Oncology $17-20 billion
Asthma/COPD $31-36 billion Hypertension $14-17 billion
3 $8,149
Other CNS Drugs $26-31 billion Diabetes $10-12 billion
Hypertension $23-26 billion Dermatology $10-12 billion
4 $7,949
Immunostimulants $22-25 billion Antiulcerants $9-11 billion
HIV Antivirals $22-25 billion Cholesterol $6-8 billion
5 $7,935 Dermatology $22-25 billion Asthma/COPD $3-5 billion
Antibiotics $18-21 billion Anti-Epileptics $3-5 billion
6 $7,863 Cholesterol $16-19 billion Antivirals excluding HIV $3-5 billion
Anti-Epileptics $15-18 billion Immunosuppressents $3-5 billion
Immunosuppressents $15-18 billion Allergy $3-5 billion
7 $7,832
Antipsychotics $13-16 billion Antidepressants $3-5 billion
Antiulcerants $12-14 billion Antiplatelet $3-5 billion
8 $7,678
Antidepressants $10-12 billion Antipsychotics $2-3 billion
Antivirals excluding HIV $8-10 billion Heparins $1-2 billion
9 $6,464 ADHD $7-9 billion Erectile Dysfunction $1-2 billion
Interferons $6-8 billion Immunostimulants $1-2 billion
10 $6,263
BRAND 67% GENERIC 21% OTHER 12% BRAND 26% GENERIC 63% OTHER 11%
5
TRENDS IN RESEARCH AND DEVELOPMENT
Revenues
Spending on R&D has increased over the last few decades but
productivity has gone down. The number of new drugs coming
on the market each year has held roughly steady or declined
since 1981. 2013
R&D expenditures, industry revenues 2010
and new chemical entities
R&D
Expenditures
2000
1990
1980
R&D
Productivity
1985 1995 2005
39 45 39 38 37 33 20 31 New Chemical
NCEs NCEs NCEs NCEs NCEs NCEs NCEs NCEs Entities
(NCEs)
10 21 11 11 13 13 10 5
Natural Natural Natural Natural Natural Natural Natural Natural
Products Products Products Products Products Products Products Products
$119.3
$81.7
Public and industry biomedical
Government contributions to
R&D expenditures, 2012 $37.1
pharmaceutical R&D remain
high across the globe. In the (USD billion)
$8.3 $48.9
US, for example, government
funding contributed to 48% $5.3
$6.1 $28.1
of all drugs approved by the $9.5
FDA and 65% of drugs that $2.0 $70.4
received priority review $53.6
$27.6
between 1988-2005. $3.3 $4.7 $6.3
$2.0 $1.4 Public
USA
Industry
CANADA AUSTRALIA CHINA JAPAN EUROPE
6
Drug discovery, including that on natural products, is increasingly done in smaller start-up
companies, academia and government laboratories, with large companies undertaking
development and marketing.
The ecosystem of life sciences R&D
Start-Ups
Venture
Capital
Genetic resources Nonprofits
sourced from: Academic
Research
• existing collections and libraries Institutions Government
• electronic data/internet Regulators
• limited field collections Large
(mainly domestic) Biopharma Clinical Trial
Government Research Sites
Research Companies
Institutes
Clinical Research Drugs
Organisations
Pharmacists,
Providers and
Health Systems
“ “
We can work here, and collect microorganisms from marine water and soil in our Collaborations provide a biotechnology company with money and
local environment. In any microenvironment the vast majority of bacteria are for resources while providing the pharmaceutical company access to cutting-
the most part unknown. This wouldn’t apply to extreme environments that tend to edge technologies. In addition, by collaborating with multiple partners,
select for very specific types of bacteria. When I worked at Lederle, anyone who pharmaceutical companies today decentralise parts of their R&D activities.
went on a trip was given a plastic bag to collect soil samples. But now we know we This decentralisation provides a mechanism by which companies can (1)
can find spectacular microbial diversity here. This wouldn’t be true for plants, but it evaluate multiple new platform or product opportunities without increasing
is definitely true for microorganisms. It would take us lifetimes to sort through what the size and cost of their own operations and (2) effectively increase the
we can get our hands on from this region, so there is no need to collect overseas. bandwidth of their operations.
– Chief Scientific Officer, – Phil Kearney, Director of Licensing and External Research,
small biotech company in the US Merck Sharp and Dohme
7
NATURAL PRODUCTS RESEARCH
70
The contribution of natural products to total drugs
60
Although support for natural Drugs approved world-wide
50
products research in large Natural products
companies has declined, the
40
contribution of natural products
to the development of new
drugs continues, and between 30
1981-2013 an average of 31%
of all new drugs annually were 20
natural products.
10
0
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
58
Number of approved drugs
44 world-wide (1981-2013) KEY
S Totally synthetic drug, often found by random
screening/modification of an existing agent
30 S/NM Totally synthetic drug/Natural Product mimic
27 S* Made by total synthesis, but the pharmacophore is/was
from a Natural Product
19 21 S*/NM Made by total synthesis, but the pharmacophore is/was
17 from a Natural Product/Natural Product mimic
V Vaccine
B Biological; usually a large (>45 residues) peptide or
protein either isolated from an organism/cell line or
5 produced by biotechnological means in a surrogate host
1 N Natural Product
NB Natural Product ‘Botanical’ (in general these have been
recently approved)
ND Derived from a Natural Product and is usually a
S S/NM S* S*/NM V B N NB ND
semisynthetic modification
20% 9% 9% 8% 2% 12% 14% 0% 26%
Source: Newman and Cragg, 2012
NATURAL PRODUCTS
8
TRENDS IN NATURAL PRODUCT RESEARCH AND DRUG DISCOVERY
Natural products research has
undergone dramatic changes in
the last 50 years, with significant
1965 1990 2015 implications for the speed, scale
and focus of R&D, and the design of
effective ABS measures.
TECHNOLOGIES
• Automated
Natural products biochemical screening Genomics-driven
chemistry • Modern analytical drug-discovery
chemistry
MATERIALS STUDIED
“
The approach we are using more and more, and
now predominantly, is to leverage the biosynthetic
pathways in microorganisms to address chemical
problems in terms of drug discovery, and to
find new compounds, or even old compounds,
and then to use genetic engineering to change
those compounds to make them better drug
NUMBERS OF COMPOUNDS ISOLATED AND STUDIED FROM A SAMPLE
candidates. This is really the trend in natural
product science… The days of going out and
collecting things – whether sponges, plants, or
=1–2 = 10 – 15 = 50 – 100 soil samples for microorganisms – and searching
for new chemicals for drug leads on a mass
scale by turning the crank a lot, those days are
behind us. There is still value there, but we need
to be smarter about how we do this. Over the
SIZE OF SAMPLES last 10-15 years the scientific community has
come to realise that the real value in organisms
Milligrams is the genes that enable organisms to make the
Kilograms Grams or less
compounds that they do. Bioprospecting in the
1990s emphasised the organism, but it really
isn’t the organism anymore, it is the genes, and
we need to incorporate this into our models for
benefit-sharing.
TIME TO TEST A SAMPLE
– Head of Natural Products Unit,
large pharmaceutical company
Months/years Days Hours
9
Traditional knowledge, once the primary lead for the
discovery of new medicines, is no longer a significant part of
industry R&D.
Use of traditional knowledge in drug development
Ethnobotanical collections
1900 Sources of
traditional Internet / databases
knowledge HIGH TECH
Literature
1960
ry
cove
dis
TK- DERIVED DRUGS rug
• Aspirin 1990 e nd
• Morphine s- driv
• Quinine nomic
• Digitoxin Ge
• Pilocarpine
TK- DERIVED DRUGS
• Vincristine 2000
• Vinblastine
• Galantamine ng
reeni
a l sc
hemic
ioc TK- DERIVED DRUGS
tedb
ma • Artemisin 2015
to
Au • Crofelemer
(approved in 2012)
LOW TECH
10INDUSTRY AND ABS
The pharmaceutical industry is more aware of
SOURCES
the Convention on Biological Diversity than many
other sectors, although this is more the case with IMS Health, 2013. Pharmerging Markets: Picking a Pathway to Success;
larger companies than with smaller. However, many IMS, 2014. Global Outlook for Medicines through 2018; Pharmaceutical
Executive, 2014. Pharma 50 Insight: The Accelerating Growth of
concerns persist within industry about legal certainty Specialty Markets; Van Arnum, P. 2014. IMS Offers a Subdued Outlook
and the need for new measures drafted to implement Page 3 for Global Pharmaceutical Industry at DCAT Week ’14. DCAT Connect,
the Nagoya Protocol to reflect the scientific, business March 25; Datamonitor, 2009. Big Pharma Mega-Mergers 1995-2014;
and legal realities of natural products research today. Baum, R. 2011. Changing Pharmaceutical Paradigms. Chemical and
Engineering News, October 4; Kearney, P. 2011. What is the Future for
the Big Pharma Model? AFG Venture Group Dispatches.
Newman, D.J. 2015. pers. com.; IMS Health, 2013. Thought
Leadership, September; IMS Health, 2014. Top 20 Global Products
2013; IMS Health, 2014. Global Outlook for Medicines through 2018;
“
The CBD has had a cooling effect on natural products Kearney, P. 2011. What is the Future for the Big Pharma Model? AFG
Page 4 Venture Group Dispatches; Noor, W. 2014. The Long Tail. PharmExec.
research, but it will not stop a company from going forward.
com; Pharma Voice, 2014. Specialty Drugs: An Evolving Commercial
There are ways to work with the treaty, the best being
Model; Van Arnum, P. 2014. IMS Offers a Subdued Outlook for Global
working directly with academic and other partners… Our Pharmaceutical Industry at DCAT Week ’14. DCAT Connect, March 25.
collaborators do the work to get the agreements in place
and so it isn’t too cumbersome and we came up with a good IMS Institute for Healthcare Informatics, 2013; www.drug.com, 2014;
agreement. The real test of the agreement didn’t happen IMS Health, 2014; Staton, T. 2014. The Top 10 Patent Losses of 2015,
because we didn’t get a drug out of it…But we could FiercePharma, www.fiercepharma.com, December 17; Krishnan, A.
operate, the research could continue. Page 5 2011, Drug Patents Expiration in 2011 and 2012 – A Bumpy Ride Ahead
for Big Pharma as Big Drugs Lose Patent Protection. IHS Healthcare,
– Head of Natural Products, pharma blog; Alazraki, M. 2011. The 10 Biggest-Selling Drugs that Are
large pharmaceutical company About to Lose Their Patent, February, www.dailyfinance.com.
PhRMA, 2015, www.phrma.org; Chakma, J., Sun, G.H., Steinberg,
“
I’ve always maintained that natural product drug discovery J.D., Sammut, S.M. and Jagsi, R. 2014. Asia’s Ascent – Global Trends
and development is an international collaborative effort – no in Biomedical R&D Expenditures. The New England Journal of Medicine
one country is dominant. That is why I think if source countries 370(1):3–6; EFPIA, 2014. www.efpia.eu; Shah, A. 2014. Pfizer and
Page 6 AstraZeneca: Innovation Will Not Follow Acquisition. Seeking Alpha, May;
can develop viable and not too restrictive policies this can be
Newman, D.J. and Cragg, G.M. 2012. Natural Products as Sources of
a win-win situation for everyone. If policies are too restrictive,
New Drugs over the 30 Years from 1981 to 2010. Journal of Natural
particularly with microbes as a source of new chemistry and Products. www.pubs.acs.org/jnp.
potential new drugs, companies will just study the microbial
resources they have in their libraries or their own backyards.
The microbial area makes protecting countries’ rights very PhRMA, 2015. www.phrma.org; Kearney, P. 2011. What is the Future for
tricky, since companies can find compounds discovered in Page 7 the Big Pharma Model? AFG Venture Group Dispatches; Noor, W. 2014.
microorganisms from one country in another – much more Pharm Exec’s Pharma 50 in 2014. PharmExec.com, June 9.
so than for plants. This is why NCI’s policy has always been
that the place where the original collection and discovery was
made is the one that should benefit, and this is even more
Newman, D.J. and Cragg, G.M. 2012. Natural Products as Sources of New
important today. Page 8 Drugs over the 30 Years from 1981 to 2010. Journal of Natural Products.
– Gordon Cragg, retired from Natural Products Branch, www.pubs.acs.org/jnp; Newman, D.J. and Cragg, G.M. in press.
US National Cancer Institute
11www.abs-initiative.info www.bio-economy.org.za www.peopleandplants.org The Access and Benefit-Sharing Key Points for Policy-Makers series has been produced Acknowledgements: Sincere thanks are due to the many to provide governments, companies, researchers, communities and others with background individuals who contributed comments and insights to the information to assist with the development of access and benefit-sharing measures to pharmaceutical industry brief. In particular, we would like implement the Nagoya Protocol. The briefs are organised around central, key points on trends to thank Bruno David, Gordon Cragg, Frank Koehn, David and practices in markets, research and development, and ABS. More detailed information on Newman and Sheo Singh. Thanks are also due to Paula these sectors can be found at: www.bio-economy.org.za; www.abs-initiative.info; Wood for her design and Jaci van Niekerk for her support www.peopleandplants.org; CBD Bioscience at a Crossroads policy briefs: and assistance in this process. https://www.cbd.int/abs/policy-brief/default.shtml/; and in the upcoming book: For further information please contact: http://www.routledge.com/books/details/9781138779099/ abs-initiative@giz.de
You can also read
