1. Access to Cancer Medications in
Low and Middle Income Countries
Gilberto de Lima Lopes, Jr., M.D., M.B.A, F.A.M.S.
Senior Consultant in Medical Oncology
Program Leader for Health Economics
Assistant Director for Clinical Research
Assistant Professor of Oncology
Johns Hopkins Singapore International Medical Centre
Johns Hopkins University School of Medicine

2. Why It Matters...

3. The “Forgotten Disease” in the
Developing World
Cancer kills more patients yearly
than Malaria, AIDS and
Tuberculosis

4. Cancer Act
Increased NCI autonomy
and funding
The Cancer Act

5. Made partnerships between government
funded agencies/ universities and private
companies possible
The Bay-Dhole Act - 1980

6. These and other actions…
Increased funding for research that
has increased our understanding of
cancer cells…
…Helping usher in an era
in which diagnostic techniques and
treatment advances improved the
treatment of patients with
cancer

7. How Are We Doing
with Cancer Control?
Childhood Cancer
Adult Cancers

8. Childhood Cancer
New cases increased 10y Survival is now
but Deaths are down 70-75%
ASCO 2009

9. In Adults in the US
In Men cancer death In Women cancer
rates have declined death rates have
nearly 21% declined 12%
Overall 2/3 of
patients with
cancer now live for
5 years or longer
vs. 1/2 a couple of
decades ago
American Cancer Society 2009-2012

10. Causes of Improvement in Cancer
Death Rates
Prevention
Vaccines: HCC, Cervical Cancer
Reduced Smoking: Lung Cancer
Early Detection
Breast and Colorectal Cancer
Better Treatment
Breast, Ovarian, Lymphoma

11. Targeted Therapy:
“The Magic Bullet”

12. www.bayer.com

13. Genomic Sequencing

14. For those of us who treat
patients in low and middle
income countries, these
improvements are but an
aspiration and hope for the
future...

15. ...Moreover, with targeted
agents, personalized
medicine and genomic
profiling, the control and
outcomes gap between high
and low income countries will
widen

16. Low and Middle Income Countries
Spend Less in Cancer Control
Per Patient As a percentage
of GNI/Capita
South America US$ 7.92 0.12%
China US$ 4.32 0.05%
India US$ 0.54 0.11%
United Kingdom US$ 183 0.51%
Japan US$ 244 0.6%
United States US$ 460 1.02%
Lopes et al. Lancet Oncology, in press 2013

17. More than 60% of cancer cases and
deaths occur in Low and Middle
Income countries and these nations
represent only 6.2% of global cancer
costs and a whopping 89% of the
cancer global expenditure gap
Lopes et al. Nature Reviews Clinical Oncology,
2013 in press, based on data from LiveStrong and
American Cancer Society

18. Why are newer medications so
expensive?

19. Treatment Costs Have Escalated
Regimen US$/3 Week Cycle
DDP + Vinorelbine 600
Carboplatin + Paclitaxel 1,000
Gefitinib 1,500
Erlotinib 2,200
Cisplatin + Pemetrexed 2,800
CP + Bevacizumab 5,800
DDP + Vinorelbine + C225 5,550
Lopes 2009.
Based on Singapore drug costs for class A patient at a
government restructured hospital

20. Birth of a Drug

21. The Cost of Developing
New Drugs
Has Escalated

22. Current Cost to Develop a Drug:
USD 1.778 Bn.
Paul et al. Nature Reviews Drug Discovery 2010

23. In the US…
Medicare and private insurers pay for
bevacizumab and for cetuximab for
instance…
.. But can the American
Society pay for ever increasing drug
costs?

24. Current Access to Innovative
Cancer Drugs in SE Asia
Summary of the First South East Asia
Cancer Care Access Network Meeting
and Survey
Lopes et al. 2011. Available at
http://www.ispor.org/regional_chapters/Singapore/documents/presenta
tion%20of-the-SE-Asia-Cancer-Care-Access-Network.pdf

25. SEACCAN Survey: Clinical
Scenarios
Colon Oxaliplatin in Stage III
Bevacizumab and Cetuximab
in Stage IV
Breast Trastuzumab in early HER2 +
Liver Sorafenib in Stage IV
Lung Erlotinib and/or Gefitinib
in advanced EGFR +

26. Access to Innovative Cancer
Drugs in SE Asia: Overall Index

27. Predictors of Access: GDP per capita
Singapore
Malaysia
Thailand
Indonesia
Philippines
Vietnam

28. Predictors of Access:
Cost-Effectiveness of Drug
Oxaliplatin
Trastuzumab
Gefitinib
Sorafenib
Cetuximab
Bevacizumab

29. SEACCAN Survey: Conclusions
Cost-effectiveness of a drug correlated with
access; while cost was a weak predictor
Conversely, cost of treatment with a drug
was predictive of overall sales, while Cost-
Effectiveness was not

30. How to Improve Cost Effectiveness?
Decreasing Cost and Increasing Value
of Cancer Medications
Making Drug Development Cheaper and
More Effective Using Biomarkers
Using generics, biosimilars, price
discrimination and access programs

32. Biomarkers Decrease Clinical Trial
Risk and Cost of Drug Development
In Breast Cancer, the use of Her2
increases the rate of success by 50%
and decreases cost by 30%
In Lung Cancer, the use of biomarkers
increases trial success rates from 11 to
50% and development cost by 27%
Lopes et al, Breast Cancer Res Treat 2012
Lopes et al, submitted ASCO 2013

33. In Asia:
Sorafenib in HCC (No biomarker)
1.6 LY at a Cost of US$ 80k/LY
Trastuzumab (Her2Neu)
1.44 QALY at US$ 19 k/QALY
Oncotype Dx in Adjuvant Breast
Generates Cost Savings
EGFR Mutation Testing and Gefitinib
Generates Cost Savings
Lopes, ASCO GI 2009, BMC Cancer 2010,
ASCO and WCLC 2011, Cancer 2012

34. Policy Options to Increase Access
Government Intervention
• Price Control and Negotiation
• Patent withdrawal – Compulsory Licensing
• Social Insurance, Subsidies, Medication Assistance
Funds
Market Based Alternatives:
• Better Private Insurance Coverage
• Greater use of Generics
• Price discrimination and Market Access Programs
• Award for Innovation
• Innovative Financing, Philanthropy
• Risk Sharing Schemes

35. Policy Options to Increase Access
Most Important and Effective Options:
Quality generics
Price Discrimination, aka, Affordable Pricing
including access programs
Adequate Insurance Coverage: Universal Coverage
and Value-Based Design

36. Universal Coverage
Pools resources from a large base of
individuals
Financial Protection from the cost of illness
In the 1980s and 1990s many countries in
Latin America and SE Asia implemented
schemes
In 2010s China and Indonesia

38. Universal Coverage: Challenges
Funding – Average USD 13,000/capita at
implementation
Increased public expenditure – In China,
for instance public share of health care
expenses increased from 35% to 60% in
the last decade
Weak institutions, favouritism, corruption
Lopes et al. Nature Reviews Clinical Oncology,
2013 in press

39. Suing the State for Coverage
Brazil and Colombia constitutions enshrine
the right to health care access
240,000 lawsuits a year in Brazil [2011] at
a cost of US$72 Million [2010]
60% of claims come from 2 richest states
Lopes et al. Nature Reviews Clinical Oncology,
2013 in press

40. Generics
Hatch-Waxman Act, 1984
The Drug Price Competition and Patient
Term Restoration Act

41. Generic Prescriptions
Generic medicines account for 69% of
all prescriptions dispensed in the
United States, yet only 16% of all
dollars spent on prescriptions.
(source: IMS Health)
Cost of Medication my drop by 80%
after introduction of a generic

42. Savings to U.S. Health Care System
1999-2008: US$734 Bn.
$140.0
$121
$120.0
$101
$100.0
$86
$78
$80.0
$65 $69
$60
$60.0 $51 $55
$49
$40.0
$20.0
$0.0
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

43. What is a Generic After All?
A generic drug is a pharmaceutical
product, usually intended to be
interchangeable with an innovator
product, that is manufactured
without a license from the innovator
company and marketed after the
expiry date of the patent or other
exclusive rights.
WHO Definition

44. How Do We Measure
Bioequivalence?

45. Accepted Bioequivalence
Parameters
US, Europe, Australia
Cmax and AUC have to fall between
80 and 120% of the originator with a
90% Confidence Interval

46. Actual Results: US FDA
12-year review of 2,070 studies
Mean +/- SD 1.00 +/- 0.06 C(max)
1.00 +/- 0.04 for AUC
Average difference in C(max) and AUC was
4.35% and 3.56%
Ann Pharmacother. 2009 Oct;43(10):1583-97.

47. Generics: Essentials Drug List
A WHO initiative
Includes several oncology drugs, such as
anthracyclines, 5FU, paclitaxel,
docetaxel, etoposide and others
Lopes et al. Nature Reviews Clinical Oncology,
2013 in press

49. Generics and Biosimilars: Challenges
Patient and Health Care Workers
Perception
Quality Issues
Except for growth factors such as G-CSF
and EPO only India has had significant
experience with Biosimilars in Oncology
Lopes et al. Nature Reviews Clinical Oncology,
2013 in press

50. Negotiating Prices:
Compulsory Licensing

51. Compulsory Licensing
WTO – TRIPS Agreement went into effect in
January 1995
Allows countries to produce/import generics while
medications are still protected by patent in
cases on grounds of public interest
Widely used for AIDS medications
Occasionally used for cancer medications
The US threatened its use to create stockpiles of
ciprofloxacin during Anthrax scare

52. Compulsory Licensing in Oncology
Thailand in 2008
Docetaxel, Letrozole, Erlotinib, [Imatinib]
Savings in excess of US$ 140 million
India in 2012
Sorafenic

53. Compulsory Licensing: Challenges
Decrease in investment
In Egypt, Pfizer pulled out of a new planned
factory
Office of the US Trade Representative
withdrew duty-free status of three Thai
products

54. Price Discrimination
[including Access Programs]
Important concept in Economics and Business
Companies charge different prices in different
markets or segments, increasing number of
consumers able to afford a product or
service
Widely used outside of health care
[Think of discounts and rebates in
electronics, for instance]

55. Price Discrimination
IMS data: Little Variation in Average Unit Price (USD)
per Country for all drugs combined [Lopes, 2011]

56. Price Discrimination
[including Access Programs]
Many pilot projects in the region have seen
increase in access and, in some, revenue
Some companies now have specific policies to
provide medications at a different cost in
low and middle income countries [GSK in all
emerging markets, ROCHE in India]

57. Price Discrimination: Challenges
Parallel Imports
Political Backlash in higher income
countries, especially in times of economic
difficulties
Lower prices might still not be low enough
in the absence of Universal Coverage and
Economic Development

58. Innovative Payment Methods
Health Technology Assessment
Increased use of HTA in LMIC
Value-Based insurance coverage
Next step!

59. Participation in Clinical Trials
Means of accessing new medications
Share of patients enrolled to clinical trials
outside of US and Europe increased from
less than 5% to approximately 30% in the
last decade
Lower cost of running trials might eventually
translate into lower drug development costs

60. Participation in Clinical Trials:
Challenges
Ethical:
informed consent, conflicts of interest
Lack of access to new medications after
trial ends

61. Drug Development Geared Towards
Emerging Markets Only
New Phenomenon
Worth Watching
Examples: Icotinib in China, Nanoxel in
India, Nimotuzumab in several countries
in Asia and Latin America

62. Public Private Partnerships:
The GAVI Alliance and The International
Finance Facility for Immunization
The global alliance for vaccines and
immunization receives funding from donors
such as the Bill and Melinda Gates
foundation and the World Bank combined
with technical assistance from the WHO and
UNICEF

63. GAVI and IFFI
Additional 325 million children immunized
5.5 million premature deaths averted
In cancer prevention, GAVI has created a
market for low cost interventions and has
helped decrease the cost of each dose of
hepatitis B vaccine to US$0.50 and of HPV
vaccine to US$5

64. Brave New World!

65. What we saw today
Cancer kills more people yearly worldwide
than Malaria, AIDS and Tuberculosis
together:
a true “Hidden Disease” in
the Developing World
Major Progress has been made in the
treatment of patients with cancer
Access is a major issue in ALL
countries

66. What We Saw Today
Chemotherapy and new rationally
designed targeted therapies have
helped improve outcomes in Cancer
A few positive and negative predictive
factors already exist and are used in
practice
Research is ongoing on better
selection of drugs for both efficacy
and toxicity

67. What We Saw Today
Cancer has a major economic impact
Generic medications have generated
substantial savings in health care
budgets and helped expand access to
care in several diseases and have a
great potential role in the
treatment of cancer
Unsafe medicines are a potential
serious problem

68. Hope for the future
Patient selection will improve and enable
us to choose therapies with greater
efficacy and safety
Better selection and fewer adverse events
will make cancer care more cost-efficient
This will be achieved with an increase in
funding for translational and clinical
research

69. Hope for the Future
Universal Coverage with value-based
pricing and wider use of
pharmacoeconomics, generics,
biosimilars and price discrimination
will increase access to cancer care
for millions of patients worldwide

70. How to do it!
It will take the whole world to control
cancer in low and middle income
countries

71. How to do it!
We need the creation of a global fund
to fight cancer, a cancer alliance and
international finance facility bringing
together donors, the world bank,
WHO, IAEA, UICC, NGOs and other
stakeholders to effectively tackle
cancer control

72. How to do it!
Join the fight!

73. “Strive not to be a success,
but rather to be of value”
Albert Einstein