WHO Essential Medicines for Cancer

1. The WHO Essential Medicines List
and Access to Cancer Medications
in Low and Middle Income Countries
Gilberto de Lima Lopes, Jr., M.D., M.B.A, F.A.M.S.
Centro Paulista de Oncologia and Hcor Onco, Oncoclinicas do Brasil Group
Johns Hopkins University School of Medicine

3. In Adults in the US
In Men cancer death
rates have dropped
21%
In Women 12%
Overall 2/3 of patients live
for 5 years or longer
compared to less than
50% several decades ago
American Cancer Society 2009-2012
Photo Credit: G Lopes, Chicago 2013

4. For those of us who treat patients in low and
middle income countries most of these
advances are an inspiration and represent
hope for the future...
...but not our current reality

5. Cancer mortality to incidence ratios
USA Europe LMICs
0.36 0.48 0.68
Lopes [Senior Author]: Global Health Equity: Cancer Care Outcomes Disparities in High,
Middle and Low Income Countries. J Clin Oncol special issue on Global Oncology, in press.
Based on Data from GLOBOCAN
Photo Credit: G Lopes, Copacabana Beach, Rio de Janeiro 2013

6. Example:
Latin
America
Lopes [co-author] in Goss et al, Planning Cancer Control in Latin America and the Caribbean Lancet Oncology 2013
Copyright: Elsevier, used with permission

7. Low and Middle Income Countries Spend
Less in Cancer Control
Lopes. Access to Cancer Medications in Low and Middle Income Countries.
Nature Rev Clin Oncol 2013. Copyright: Nature Publishing, used with permission
Numbers represent economic
burden per cancer patient in
US$ (and as a percentage of
GDP/Capita)

8. Low and Middle Income countries represent
more than half of cancer cases, 6.2% of global
cancer costs and 89% of the cancer global
expenditure gap

9. UN Resolution 61/225 on Diabetes (2006)
Political Recognition
UN Political Declaration on NCDs
• Historic political commitment for cancer
and the other NCDs
• 22 action orientated commitments
covering prevention, treatment and care
• A springboard to set a new Global NCD
Framework

10. “What gets measured, gets done”
WHO DG, Margaret Chan

11. UN Resolution 61/225 on Diabetes (2006)
Political Recognition
Outline
Background
The WHO model EML
The 2015 Committee Decision and How we got here
How can LMICs afford the medications in the list?

12. What is the WHO model EML?
Definition
“Essential medicines are those that satisfy the priority health care needs of the
population. They are selected with due regard to public health relevance,
evidence on efficacy and safety, and comparative cost-effectiveness.”
Former WHO Model List had 30 cancer medicines
• Full reviews of the cancer medicines on the WHO EML list had been carried in
1984, 1994 and 1999
References:
www.who.int/medicines/publications/essentialmedicines
Shulman, Wagner, Barr, Lopes, Torode, Magrini et al. Proposing Essential Medicines to Treat Cancer:
Methodologies, Processes, and Outcomes. J Clin Oncol 2015, special issue on Global Oncology. In Press.

13. What opportunity does the model EML
provide for national advocacy?
At least 156 out of 194 Member States have national EMLs
Model list is a response to MS requests – since 1977
Guide the definition of national EMLs: identify priority
medicines for procurement and prioritization at the
institutional level
A central component of Universal Health Coverage

14. 2012-2013 WHO EML cycle
 Applications for the addition of trastuzumab and imatinib submitted jointly by
DFCI and UICC in November 2012
 Campaign to secure support: 20 letters of support received and posted on WHO
website from ASCO, ESMO, BHGI, PIH, SLACOM, Ministry of Health of
Rwanda, Max Foundation and others
 Presentation at the Expert Committee meeting in April 2013 to defend the two
applications and section review proposal
Thanks to the financial support of LIVESTRONG

15. The request for a section review
Report of the 19th Expert Committee (oct. 2013)
 Acknowledgement of the growing public health importance of
cancer and the need for countries to consider the addition of
highly effective but high cost cancer drugs in the context of
evidence-based treatment regimens;
 Urgent need for a review of sub-section 8.2 in terms of
structure and medicines included – decision on
trastuzumab and imatinib reported until the review is
completed;

16. UICC Task Team
The UICC-convened task force was charged with creating a new
framework for evaluation of drugs for inclusion in the WHO
Essentials Medicines List
Members of the Task team include:
DFCI, UICC, ASCO, NCCN International, NCI, ESMO -
workingin collaboration with the WHO EML Secretariat

17. 2014-2015 – Timeline
May 14 June
July –
Nov
Dec-
March 15
April
May-
June1
5
Concept
note
accepted
by WHO
• Agreed on
core set of
cancer types
and set of
regimens
• Gap analysis
vs EML
Expert
Committee
Review
Expert
Committee
Meeting
Decision
made and
results
disseminated
•Feedback WHO
• Prepare & submit
proposals for
change by Nov
2014

18. Proposed EML Framework
Four Main Dimensions with Three Levels Each:
 Efficacy and Safety of Therapy
Cure, Near Cure, Prolongation of Survival/Palliation of Symptoms
Adequate Safety
 Burden of Disease
Low, Mid and High Incidence
 Cost Effectiveness of Drug/Regimen
Highly Cost Effective, Cost Effective and Not Cost Effective
 Resource Requirements for Drug Use
Low, Middle and High requirement levels

19. Low Medium High
Incidence of Disease
Treatment Goal
Cure or “near cure”
Significant
prolongation of
survival
Palliation of
symptoms with
small benefit in
survival
Leukemia and
Lymphomas in Children
HIGHEST PRIORITY
Adjuvant Breast Cancer
CML
Adjuvant Colon Cancer
Lymphomas
in Adults
Stage III Ovarian Cancer
Metastatic Breast Cancer
HIGH
PRIORITY
Metastatic
Pancreatic Cancer
Metastatic
Lung Cancer
LOWEST PRIORITY
GIST
Metastatic Prostate Cancer
Metastatic
Bladder Cancer
LOW PRIORITY
Low priority could become High Priority if Highly Cost Effective

20. Highly Cost Effective
[Cost/QALY equal or less than GDP/capita]
Cost Effective
[Cost/QALY up to 3x GDP/Capita]
Not Cost Effective
[Cost/QALY > 3x GDP/Capita]
P
R
I
O
R
I
T
Y
1. Different levels for low income, low middle income and high middle income countries.
2. Health systems should see the CE evaluation as a tool to discuss/negotiate prices of priority medications
not as a rigid recommendation.
FOR EACH CATEGORY

21. BHGI-Like Approach: Metastatic Colon Cancer
Level Drugs
Basic BSC Alone
Limited 5FU Alone
Enhanced + Oxaliplatin, Irinotecan
Maximal + Cetuximab/Panitumumab,
Bevacizumab
DecreasingCE
ICER
US$
450
44,500
80,000
Source: Management of colon cancer: resource-stratified guidelines from the Asian
Oncology Summit 2012. Lopes [Senior Author] in Ku et al, Lancet Oncology Vol 13
November 2012

22. Disease-based Briefings Prepared for 29 Types of Cancer
• AML and APL (Adult and Pediatric)
• Chronic Lymphocytic Leukemia
• Chronic Myelogenous Leukemia (Adult and Pediatric)
• Diffuse Large B-Cell Lymphoma
• Early Stage Breast Cancer
• Early Stage Cervical Cancer
• Early Stage Colon Cancer
• Early Stage Rectal Cancer
• Epithelial Ovarian Cancer
• Follicular Lymphoma
• Gastrointestinal Stromal Tumor
• Gestational Trophoblastic Neoplasia
• Locally Advanced Sq Carcinoma of the Head and Neck
• Hodgkin Lymphoma
• Kaposi Sarcoma
• Metastatic Breast Cancer
• Metastatic Colorectal Cancer
• Metastatic Prostate Cancer
• Nasopharyngeal Carcinoma
• Non-small Cell Lung Cancer
• Ovarian Germ Cell Tumors (Adult and
Pediatric)
• Testicular Germ Cell Tumors (Adult and
Pediatric)
Pediatric-Specific
• Acute Lymphoblastic Leukemia
• Burkitt Lymphoma
• Ewing Sarcoma
• Hodgkin Lymphoma
• Osteosarcoma
• Retinoblastoma
• Rhabdomyosarcoma
• Wilms Tumor

23. Global participation
Authors and reviewers were experts from all 6 inhabited continents

26. The Task Force Suggested the
Inclusion of 22 Medications

27. 16 Have Been Approved
“Following a review requested by the previous Expert Committee in
2013, the Committee recommended the addition of 16 new
medicines and endorsed the use of 30 medicines listed currently
as part of proven clinically effective treatment regimens. These
medicines will be included on the complementary list of the EML
for the treatment of specific cancers. The Committee
recommended that the Model Lists should specify the cancers for
which use of each medicine is recommended.”
WHO, May 2015

28. A New Total of 46 drugs
*Denotes newly added
Allopurinol, Anastrozole*, Asparaginase, ATRA*, Bendamustine*,
Bicalutamide*, Bleomycin, Calcium folinate, Capecitabine*, Carboplatin,
Chlorambucil, Cisplatin*, Cyclophosphamide, Cytarabine, Dacarbazine,
Dactinomycin, Daunorubicin, Dexamethasone, Docetaxel, Doxorubicin,
Etoposide, Fludarabine*, Fluorouracil, G-CSF*, Gemcitabine*,
Hydrocortisone, Hydroxycarbamide, Ifosfamide, Imatinib*, Irinotecan*,
Leuprolide* (Class), Mercaptopurine, Mesna, Methotrexate,
Methylprednisolone, Oxaliplatin*, Paclitaxel, Prednisolone, Procarbazine,
Rituximab*, Tamoxifen, Thioguanine, Trastuzumab*, Vinblastine, Vincristine,
Vinorebine

29. High Cost Medications
Including:
Imatinib for CML and GIST
Trastuzumab for early and advanced HER2 Breast
Cancer
Rituximab for lymphomas

30. The 6 That Were Not
Nilotinib and Dasatinib for CML
Arsenic Trioxide for APL
Gefitinib and Erlotinib for EGFR mutated NSCLC
Diethylstilbestrol for prostate cancer

31. Photo Credit: G Lopes, Garden @ WHO, 2015

32. Our Biggest Challenge Starts Now!

33. Cost Implications of Adding Trastuzumab
UICC WHO EML Task Force. http://www.who.int/selection_medicines/committees/expert/20/applications/cancer/en/

34. Cost Implications of Adding Rituximab
UICC WHO EML Task Force. http://www.who.int/selection_medicines/committees/expert/20/applications/cancer/en/

35. Birth of a Drug
1
Approved
Drug
10,000
Compounds in
Drug
Discovery
250 drug
candidates in
pre-clinical
testing
5 drugs in
Phase I-III trials
IND
Submission
10-15 years
Munos. Lessons from 60 years of pharmaceutical innovation. Nat Rev Drug Disc 2009
Pammolli. The productivity crisis in phrmaceutical R&D. Nat Rev Drug Disc 2011

36. The Cost of Developing New Drugs Has Escalated
US$ 138 Million
1975
DiMasi et al. The Price of Innovation: New Estimates of Drug Development Costs. J Heath Econ 2003 and press release from the
Tufts group in 2015
US$ 318 Million
1987
US$ 802 Million
2000
US$ 2.6 billion
2015

37. 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/presentation%20of-the-SE-
Asia-Cancer-Care-Access-Network.pdf

38. Access to Innovative Cancer Drugs
in SE Asia: Overall Index
0
0.1
0.2
0.3
0.4
0.5
0.6

39. 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

40. Biomarkers Improve Cost-Effectiveness
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
and generates societal income
in the adjuvant setting
Oncotype Dx in Adjuvant Breast: Generates Cost Savings
EGFR Mutation Testing and EGFR TKI: Generates Cost Savings
Lopes, JCO 2007, ASCO GI 2009, BMC Cancer 2010, ASCO and WCLC 2011, Cancer 2012

41. 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 60% and decreases
development cost by 27%
Parker, Lopes et al, Breast Cancer Res Treat 2012
Falconi, Lopes et al, ASCO 2013, WCLC 2013, JTO 2014

42. Copyright Nature Publishing, used with permission

43. Options to Increase Access
Copyright Nature Publishing, used with permission

44. How to Increase Access
Most Important and Effective Options:
Quality generics (and Compulsory Licensing?)
Price Discrimination, aka, Affordable Pricing
Adequate Healthcare Funding:
Universal Coverage
Value-Based Insurance Design
PPP - Global Fund to fight cancer in LMIC
Lopes. Access to Cancer Medications in Low and Middle Income Countries. Nature Rev Clin Oncol 2013

45. Generics
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
In the US the use of generics has saved greater than
US$ 734 billion over a decade

46. Potential Savings with Generics in
Low and Middle Income Countries Are Significant
Generic substitution for four commonly used drugs can
amount to savings in excess of US$800 million in India
every year
In one small retrospective study and one small prospective
registry, efficacy and safety of commonly used drugs was
equivalent with generic or originator drug in India
Lopes G. Ann Oncol 2013 and BMC Cancer 2015 (submitted)

47. 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. Access to Cancer Medications in Low and Middle Income Countries. Nature Rev Clin Oncol 2013

48. Compulsory Licensing
WTO – TRIPS Agreement went into effect in January 1995
Allows countries to produce/import generics while medications
are still protected by patent 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
Lopes. ASCO Connection 2014.
Compulsory Licensing: A Double Edged Sword in the fight for access to cancer medications in low- and middle-income countries.

49. Compulsory Licensing in Oncology
Thailand in 2008
Docetaxel, Letrozole, Erlotinib, [Imatinib]
Savings in excess of US$ 140 million
India in 2012
Sorafenib
Lopes. ASCO Connection 2014.
Compulsory Licensing: A Double Edged Sword in the fight for access to cancer medications in low- and middle-income countries.

50. Compulsory Licensing: Challenges
Decrease in investment
In Egypt, Pfizer pulled out of a new planned factory when
the country issued a compulsory license for Sildenafil
Office of the US Trade Representative withdrew duty-free
status of three Thai products
Lopes. ASCO Connection 2014.
Compulsory Licensing: A Double Edged Sword in the fight for access to cancer medications in low- and middle-income countries.

51. 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]

52. Price Discrimination
IMS data: Little Variation in Average Unit Price (USD)
per Country for all drugs combined [Lopes, 2011]
0
50
100
150
200
Index
Singapore
Malaysia
Thailand
Indonesia
Philippines
Vietnam

53. Price Discrimination
[including Access Programs]
Many pilot projects have led to an increase in access and,
in some cases, 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]

54. 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

55. 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

56. 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

57. Proposal:
A Global Fund and Alliance
to Fight Cancer in LMIC
A Global Fund to Fight Cancer would—through
engagement, goal setting and multiple-stakeholder
involvement—provide recipient countries with incentives
to create and develop their health and human capital
infrastructures with adequate technical support.

58. Global Fund to Fight Cancer in LMIC
The alliance of funding and technical partners would unify
efforts, support the creation and implementation of cancer
control plans and make available cancer interventions in
a stepwise fashion, led in the most cost-effective way

59. Global Fund to Fight Cancer in LMIC
The alliance could also help create a functioning market for
the provision of low-cost interventions where none exists
today, fostering innovation and lowering costs.
Furthermore, we envisage that the alliance would support
negotiations with industry to facilitate the implementation
of tiered pricing schemes in low-income countries.

60. Photo Credit: G Lopes, Kolkata, India, 2013

61. What we saw today
Cancer is a major global health care issue
Access is or will be a major issue in ALL countries
The WHO Essential Medicines List helps set a starting point,
not the final destination and is a major victory in our global
public health fight against cancer
Low Income Countries in particular will need help accessing
all of the drugs on the list
A Series of Policy Options exist that could help them do so

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

63. 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,
Industry and other stakeholders to effectively
tackle cancer control in low income countries

64. How you can help:

65. Thank You!
Strive not to be a success,
but rather to be of value.
Albert Einstein