Access to Cancer Medications in Access to Cancer Medications in Low and Middle Income CountriesLow and Middle Income Countries

Gilberto de Lima Lopes, JrGilberto de Lima Lopes, Jr., M.D., M.B.A, F.A.M.S.., M.D., M.B.A, F.A.M.S.

Senior Consultant in Medical OncologySenior Consultant in Medical OncologyProgram Leader for Health EconomicsProgram Leader for Health EconomicsAssistant Director for Clinical ResearchAssistant Director for Clinical Research

Assistant Professor of OncologyAssistant Professor of OncologyJohns Hopkins Singapore International Medical CentreJohns Hopkins Singapore International Medical Centre

Johns Hopkins University School of MedicineJohns Hopkins University School of Medicine

Why It Matters...Why It Matters...

The “Forgotten Disease” in the The “Forgotten Disease” in the Developing WorldDeveloping World

Cancer kills more patients yearly Cancer kills more patients yearly than Malaria, AIDS and than Malaria, AIDS and TuberculosisTuberculosis

Cancer ActCancer ActIncreased NCI autonomy Increased NCI autonomy

and fundingand funding

The Cancer ActThe Cancer Act

The Bay-Dhole Act - 1980The Bay-Dhole Act - 1980

Made partnerships between government Made partnerships between government funded agencies/ universities and private funded agencies/ universities and private companies possiblecompanies possible

These and other actions…These and other actions…

Increased funding for research that Increased funding for research that has increased our understanding of has increased our understanding of cancer cells…cancer cells…

……Helping usher in an Helping usher in an era in which diagnostic techniques era in which diagnostic techniques and treatment advances improved and treatment advances improved the treatment of patients with the treatment of patients with cancer cancer

How Are We Doing How Are We Doing with Cancer Control?with Cancer Control?

Childhood CancerChildhood Cancer

Adult CancersAdult Cancers

Childhood CancerChildhood Cancer

New cases increasedNew cases increased

but Deaths are downbut Deaths are down10y Survival is now 10y Survival is now

70-75%70-75%

ASCO 2009ASCO 2009

In Adults in the USIn Adults in the US

In Men cancer death In Men cancer death rates have declined rates have declined nearly 21% nearly 21%

In Women cancer In Women cancer death rates have death rates have declined 12%declined 12%

Overall 2/3 of Overall 2/3 of patients with patients with cancer now live for cancer now live for 5 years or longer 5 years or longer vs. 1/2 a couple of vs. 1/2 a couple of decades ago decades ago

American Cancer Society 2009-2012American Cancer Society 2009-2012

Causes of Improvement in Cancer Causes of Improvement in Cancer Death RatesDeath Rates

PreventionPrevention

Vaccines: HCC, Cervical CancerVaccines: HCC, Cervical Cancer

Reduced Smoking: Lung CancerReduced Smoking: Lung Cancer

Early DetectionEarly Detection

Breast and Colorectal CancerBreast and Colorectal Cancer

Better TreatmentBetter Treatment

Breast, Ovarian, LymphomaBreast, Ovarian, Lymphoma

Targeted Therapy:Targeted Therapy:““The Magic Bullet”The Magic Bullet”

www.bayer.comwww.bayer.com

Genomic SequencingGenomic Sequencing

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

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

Low and Middle Income Countries Low and Middle Income Countries Spend Less in Cancer ControlSpend Less in Cancer Control

Per Patient Per Patient As a percentage As a percentage of GNI/Capitaof GNI/Capita

South America South America US$ 7.92US$ 7.92 0.12%0.12%China China US$ 4.32US$ 4.32 0.05%0.05%India India US$ 0.54US$ 0.54 0.11%0.11%United Kingdom US$ 183United Kingdom US$ 183 0.51%0.51%Japan Japan US$ 244US$ 244 0.6%0.6%United States United States US$ 460US$ 460 1.02%1.02%

Lopes et al. Lancet Oncology, in press 2013Lopes et al. Lancet Oncology, in press 2013

More than 60% of cancer cases and More than 60% of cancer cases and deaths occur in Low and Middle deaths occur in Low and Middle Income countries and these nations Income countries and these nations represent only 6.2% of global cancer represent only 6.2% of global cancer costs and a whopping 89% of the costs and a whopping 89% of the cancer global expenditure gapcancer global expenditure gap

Lopes et al. Nature Reviews Clinical Oncology, Lopes et al. Nature Reviews Clinical Oncology,

2013 in press, based on data from LiveStrong and 2013 in press, based on data from LiveStrong and

American Cancer SocietyAmerican Cancer Society

Why are newer medications so Why are newer medications so expensive?expensive?

Treatment Costs Have EscalatedTreatment Costs Have Escalated

Lopes 2009. Lopes 2009. Based on Singapore drug costs for class A patient at a Based on Singapore drug costs for class A patient at a

government restructured hospital government restructured hospital

RegimenRegimen US$/3 Week CycleUS$/3 Week Cycle

DDP + VinorelbineDDP + Vinorelbine 600 600 Carboplatin + PaclitaxelCarboplatin + Paclitaxel 1,0001,000GefitinibGefitinib 1,500 1,500 ErlotinibErlotinib 2,200 2,200 Cisplatin + PemetrexedCisplatin + Pemetrexed 2,8002,800CP + BevacizumabCP + Bevacizumab 5,8005,800DDP + Vinorelbine + C225DDP + Vinorelbine + C225 5,5505,550

Birth of a DrugBirth of a Drug

The Cost of Developing The Cost of Developing New Drugs New Drugs

Has EscalatedHas Escalated

Current Cost to Develop a Drug: Current Cost to Develop a Drug: USD 1.778 Bn.USD 1.778 Bn.

Paul et al. Nature Reviews Drug Discovery 2010Paul et al. Nature Reviews Drug Discovery 2010

In the US…In the US…

Medicare and private insurers pay for Medicare and private insurers pay for bevacizumab and for cetuximab for bevacizumab and for cetuximab for instance…instance…

.. But can the American .. But can the American Society pay for ever increasing drug Society pay for ever increasing drug costs?costs?

Current Access to Innovative Current Access to Innovative Cancer Drugs in SE AsiaCancer Drugs in SE Asia

Summary of the First South East Asia Summary of the First South East Asia Cancer Care Access Network Meeting Cancer Care Access Network Meeting and Surveyand Survey

Lopes et al. 2011. Available atLopes et al. 2011. Available at

http://www.ispor.org/regional_chapters/Singapore/documents/http://www.ispor.org/regional_chapters/Singapore/documents/presentation%20of-the-SE-Asia-Cancer-Care-Access-Network.pdf presentation%20of-the-SE-Asia-Cancer-Care-Access-Network.pdf

SEACCAN Survey: Clinical SEACCAN Survey: Clinical ScenariosScenarios

ColonColon Oxaliplatin in Stage III Oxaliplatin in Stage III

Bevacizumab and Cetuximab Bevacizumab and Cetuximab in Stage IVin Stage IV

BreastBreast Trastuzumab in early HER2 +Trastuzumab in early HER2 +

LiverLiver Sorafenib in Stage IVSorafenib in Stage IV

LungLung Erlotinib and/or Gefitinib Erlotinib and/or Gefitinib in advanced EGFR +in advanced EGFR +

Access to Innovative Cancer Access to Innovative Cancer Drugs in SE Asia: Overall IndexDrugs in SE Asia: Overall Index

Predictors of Access: GDP per capitaPredictors of Access: GDP per capita

SingaporeSingapore

MalaysiaMalaysia

ThailandThailand

IndonesiaIndonesiaPhilippinesPhilippines

VietnamVietnam

Predictors of Access: Predictors of Access: Cost-Effectiveness of DrugCost-Effectiveness of Drug

OxaliplatinOxaliplatin

TrastuzumabTrastuzumab

GefitinibGefitinib

CetuximabCetuximab

SorafenibSorafenib

BevacizumabBevacizumab

SEACCAN Survey: ConclusionsSEACCAN Survey: Conclusions

Cost-effectiveness of a drug correlated with Cost-effectiveness of a drug correlated with access; while cost was a weak predictoraccess; while cost was a weak predictor

Conversely, cost of treatment with a drug Conversely, cost of treatment with a drug was predictive of overall sales, while Cost-was predictive of overall sales, while Cost-Effectiveness was notEffectiveness was not

How to Improve Cost Effectiveness?How to Improve Cost Effectiveness?

Decreasing Cost and Increasing Value Decreasing Cost and Increasing Value of Cancer Medicationsof Cancer Medications

Making Drug Development Cheaper and Making Drug Development Cheaper and More Effective Using BiomarkersMore Effective Using Biomarkers

Using generics, biosimilars, price Using generics, biosimilars, price discrimination and access programsdiscrimination and access programs

Biomarkers Decrease Clinical Trial Biomarkers Decrease Clinical Trial Risk and Cost of Drug DevelopmentRisk and Cost of Drug Development

In Breast Cancer, the use of Her2 In Breast Cancer, the use of Her2 increases the rate of success by 50% increases the rate of success by 50% and decreases cost by 30%and decreases cost by 30%

In Lung Cancer, the use of biomarkers In Lung Cancer, the use of biomarkers increases trial success rates from 11 to increases trial success rates from 11 to 50% and development cost by 27%50% and development cost by 27%

Lopes et al, Breast Cancer Res Treat 2012Lopes et al, Breast Cancer Res Treat 2012

Lopes et al, submitted ASCO 2013Lopes et al, submitted ASCO 2013

In Asia:In Asia:

Sorafenib in HCC (No biomarker)Sorafenib in HCC (No biomarker)

1.6 LY at a Cost of US$ 80k/LY1.6 LY at a Cost of US$ 80k/LY

Trastuzumab (Her2Neu)Trastuzumab (Her2Neu)

1.44 QALY at US$ 19 k/QALY1.44 QALY at US$ 19 k/QALY

Oncotype Dx in Adjuvant BreastOncotype Dx in Adjuvant Breast

Generates Cost Savings Generates Cost Savings

EGFR Mutation Testing and GefitinibEGFR Mutation Testing and Gefitinib

Generates Cost SavingsGenerates Cost Savings

Lopes, ASCO GI 2009, BMC Cancer 2010, Lopes, ASCO GI 2009, BMC Cancer 2010, ASCO and WCLC 2011, Cancer 2012ASCO and WCLC 2011, Cancer 2012

Policy Options to Increase AccessPolicy Options to Increase Access

Government InterventionGovernment Intervention• Price Control and NegotiationPrice Control and Negotiation

• Patent withdrawal – Compulsory LicensingPatent withdrawal – Compulsory Licensing

• Social Insurance, Subsidies, Medication Assistance Social Insurance, Subsidies, Medication Assistance FundsFunds

Market Based Alternatives: Market Based Alternatives: • Better Private Insurance CoverageBetter Private Insurance Coverage

• Greater use of GenericsGreater use of Generics

• Price discrimination and Market Access ProgramsPrice discrimination and Market Access Programs

• Award for Innovation Award for Innovation

• Innovative Financing, PhilanthropyInnovative Financing, Philanthropy

• Risk Sharing SchemesRisk Sharing Schemes

Policy Options to Increase AccessPolicy Options to Increase Access

Most Important and Effective Options:Most Important and Effective Options:

Quality genericsQuality generics

Price Discrimination, aka, Affordable Pricing Price Discrimination, aka, Affordable Pricing including access programsincluding access programs

Adequate Insurance Coverage: Universal Coverage Adequate Insurance Coverage: Universal Coverage and Value-Based Designand Value-Based Design

Universal CoverageUniversal Coverage

Pools resources from a large base of Pools resources from a large base of individualsindividuals

Financial Protection from the cost of illnessFinancial Protection from the cost of illness

In the 1980s and 1990s many countries in In the 1980s and 1990s many countries in Latin America and SE Asia implemented Latin America and SE Asia implemented schemesschemes

In 2010s China and IndonesiaIn 2010s China and Indonesia

Universal Coverage: ChallengesUniversal Coverage: Challenges

Funding – Average USD 13,000/capita at Funding – Average USD 13,000/capita at implementationimplementation

Increased public expenditure – In China, for Increased public expenditure – In China, for instance public share of health care instance public share of health care expenses increased from 35% to 60% in expenses increased from 35% to 60% in the last decadethe last decade

Weak institutions, favouritism, corruptionWeak institutions, favouritism, corruption

Lopes et al. Nature Reviews Clinical Oncology, Lopes et al. Nature Reviews Clinical Oncology,

2013 in press2013 in press

Suing the State for CoverageSuing the State for Coverage

Brazil and Colombia constitutions enshrine Brazil and Colombia constitutions enshrine the right to health care accessthe right to health care access

240,000 lawsuits a year in Brazil [2011] at 240,000 lawsuits a year in Brazil [2011] at a cost of US$72 Million [2010]a cost of US$72 Million [2010]

60% of claims come from 2 richest states60% of claims come from 2 richest states

Lopes et al. Nature Reviews Clinical Oncology, Lopes et al. Nature Reviews Clinical Oncology,

2013 in press2013 in press

GenericsGenerics

Hatch-Waxman Act, 1984Hatch-Waxman Act, 1984The Drug Price Competition and Patient The Drug Price Competition and Patient

Term Restoration ActTerm Restoration Act

Generic PrescriptionsGeneric Prescriptions

Generic medicines account for 69% of Generic medicines account for 69% of all prescriptions dispensed in the all prescriptions dispensed in the United States, yet only 16% of all United States, yet only 16% of all dollars spent on prescriptions. dollars spent on prescriptions. (source: IMS Health)(source: IMS Health)

Cost of Medication my drop by 80% Cost of Medication my drop by 80% after introduction of a generic after introduction of a generic

Savings to U.S. Health Care SystemSavings to U.S. Health Care System1999-2008: US$734 Bn.1999-2008: US$734 Bn.

$49 $51 $55$60

$65 $69$78

$86

$101

$121

$0.0

$20.0

$40.0

$60.0

$80.0

$100.0

$120.0

$140.0

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

What is a Generic After All?What is a Generic After All?

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

WHO DefinitionWHO Definition

How Do We Measure How Do We Measure Bioequivalence?Bioequivalence?

Accepted Bioequivalence Accepted Bioequivalence ParametersParameters

US, Europe, AustraliaUS, Europe, Australia

Cmax and AUC have to fall between Cmax and AUC have to fall between 80 and 120% of the originator with a 80 and 120% of the originator with a 90% Confidence Interval 90% Confidence Interval

Actual Results: US FDAActual Results: US FDA

12-year review of 12-year review of 2,070 studies2,070 studies

Mean +/- SDMean +/- SD 1.00 +/- 0.06 C(max)1.00 +/- 0.06 C(max)

1.00 +/- 0.04 for AUC1.00 +/- 0.04 for AUC

Average difference in C(max) and AUC was Average difference in C(max) and AUC was 4.35% and 3.56%4.35% and 3.56%

Ann Pharmacother. 2009 Oct;43(10):1583-97.  2009 Oct;43(10):1583-97.

Generics: Essentials Drug ListGenerics: Essentials Drug List

A WHO initiativeA WHO initiative

Includes several oncology drugs, such as Includes several oncology drugs, such as anthracyclines, 5FU, paclitaxel, docetaxel, anthracyclines, 5FU, paclitaxel, docetaxel, etoposide and othersetoposide and others

Lopes et al. Nature Reviews Clinical Oncology, Lopes et al. Nature Reviews Clinical Oncology,

2013 in press2013 in press

Generics and Biosimilars: ChallengesGenerics and Biosimilars: Challenges

Patient and Health Care Workers PerceptionPatient and Health Care Workers Perception

Quality IssuesQuality Issues

Except for growth factors such as G-CSF Except for growth factors such as G-CSF and EPO only India has had significant and EPO only India has had significant experience with Biosimilars in Oncologyexperience with Biosimilars in Oncology

Lopes et al. Nature Reviews Clinical Oncology, Lopes et al. Nature Reviews Clinical Oncology,

2013 in press2013 in press

Negotiating Prices: Negotiating Prices: Compulsory LicensingCompulsory Licensing

Compulsory LicensingCompulsory Licensing

WTO – TRIPS Agreement went into effect in WTO – TRIPS Agreement went into effect in January 1995January 1995

Allows countries to produce/import generics while Allows countries to produce/import generics while medications are still protected by patent in medications are still protected by patent in cases on grounds of public interestcases on grounds of public interest

Widely used for AIDS medicationsWidely used for AIDS medications

Occasionally used for cancer medicationsOccasionally used for cancer medications

The US threatened its use to create stockpiles of The US threatened its use to create stockpiles of ciprofloxacin during Anthrax scareciprofloxacin during Anthrax scare

Compulsory Licensing in OncologyCompulsory Licensing in Oncology

Thailand in 2008Thailand in 2008

Docetaxel, Letrozole, Erlotinib, [Imatinib]Docetaxel, Letrozole, Erlotinib, [Imatinib]

Savings in excess of US$ 140 million Savings in excess of US$ 140 million

India in 2012India in 2012

SorafenicSorafenic

Compulsory Licensing: ChallengesCompulsory Licensing: Challenges

Decrease in investmentDecrease in investment

In Egypt, Pfizer pulled out of a new planned In Egypt, Pfizer pulled out of a new planned factoryfactory

Office of the US Trade Representative Office of the US Trade Representative withdrew duty-free status of three Thai withdrew duty-free status of three Thai productsproducts

Price Discrimination Price Discrimination [including Access Programs][including Access Programs]

Important concept in Economics and BusinessImportant concept in Economics and Business

Companies charge different prices in different Companies charge different prices in different markets or segments, increasing number of markets or segments, increasing number of consumers able to afford a product or consumers able to afford a product or serviceservice

Widely used outside of health careWidely used outside of health care

[Think of discounts and rebates in [Think of discounts and rebates in electronics, for instance] electronics, for instance]

Price DiscriminationPrice Discrimination

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

Price Discrimination Price Discrimination [including Access Programs][including Access Programs]

Many pilot projects in the region have seen Many pilot projects in the region have seen increase in access and, in some, revenueincrease in access and, in some, revenue

Some companies now have specific policies to Some companies now have specific policies to provide medications at a different cost in provide medications at a different cost in low and middle income countries [GSK in all low and middle income countries [GSK in all emerging markets, ROCHE in India]emerging markets, ROCHE in India]

Price Discrimination: ChallengesPrice Discrimination: Challenges

Parallel ImportsParallel Imports

Political Backlash in higher income Political Backlash in higher income countries, especially in times of economic countries, especially in times of economic difficultiesdifficulties

Lower prices might still not be low enough Lower prices might still not be low enough in the absence of Universal Coverage and in the absence of Universal Coverage and Economic DevelopmentEconomic Development

Innovative Payment MethodsInnovative Payment Methods

Health Technology AssessmentHealth Technology Assessment

Increased use of HTA in LMICIncreased use of HTA in LMIC

Value-Based insurance coverageValue-Based insurance coverage

Next step!Next step!

Participation in Clinical TrialsParticipation in Clinical Trials

Means of accessing new medicationsMeans of accessing new medications

Share of patients enrolled to clinical trials Share of patients enrolled to clinical trials outside of US and Europe increased from outside of US and Europe increased from less than 5% to approximately 30% in the less than 5% to approximately 30% in the last decadelast decade

Lower cost of running trials might eventually Lower cost of running trials might eventually translate into lower drug development coststranslate into lower drug development costs

Participation in Clinical Trials: Participation in Clinical Trials: ChallengesChallenges

Ethical: Ethical:

informed consent, conflicts of interestinformed consent, conflicts of interest

Lack of access to new medications after Lack of access to new medications after trial endstrial ends

Drug Development Geared Towards Drug Development Geared Towards Emerging Markets OnlyEmerging Markets Only

New PhenomenonNew Phenomenon

Worth WatchingWorth Watching

Examples: Icotinib in China, Nanoxel in Examples: Icotinib in China, Nanoxel in India, Nimotuzumab in several countries India, Nimotuzumab in several countries in Asia and Latin Americain Asia and Latin America

Public Private Partnerships: Public Private Partnerships: The GAVI Alliance and The International The GAVI Alliance and The International

Finance Facility for ImmunizationFinance Facility for Immunization

The global alliance for vaccines and The global alliance for vaccines and immunization receives funding from donors immunization receives funding from donors such as the Bill and Melinda Gates such as the Bill and Melinda Gates foundation and the World Bank combined foundation and the World Bank combined with technical assistance from the WHO and with technical assistance from the WHO and UNICEFUNICEF

GAVI and IFFIGAVI and IFFI

Additional 325 million children immunizedAdditional 325 million children immunized

5.5 million premature deaths averted5.5 million premature deaths averted

In cancer prevention, GAVI has created a In cancer prevention, GAVI has created a market for low cost interventions and has market for low cost interventions and has helped decrease the cost of each dose of helped decrease the cost of each dose of hepatitis B vaccine to US$0.50 and of HPV hepatitis B vaccine to US$0.50 and of HPV vaccine to US$5vaccine to US$5

Brave New World!Brave New World!

What we saw todayWhat we saw today

Cancer kills more people yearly worldwide Cancer kills more people yearly worldwide than Malaria, AIDS and Tuberculosis than Malaria, AIDS and Tuberculosis together:together:

a true “Hidden Disease” in a true “Hidden Disease” in the Developing Worldthe Developing World

Major Progress has been made in the Major Progress has been made in the treatment of patients with cancertreatment of patients with cancer

Access is a major issue in ALL countriesAccess is a major issue in ALL countries

What We Saw TodayWhat We Saw Today

Chemotherapy and new rationally Chemotherapy and new rationally designed targeted therapies have designed targeted therapies have helped improve outcomes in Cancerhelped improve outcomes in Cancer

A few positive and negative predictive A few positive and negative predictive factors already exist and are used in factors already exist and are used in practicepractice

Research is ongoing on better Research is ongoing on better selection of drugs for both efficacy selection of drugs for both efficacy and toxicityand toxicity

What We Saw TodayWhat We Saw Today

Cancer has a major economic impactCancer has a major economic impact

Generic medications have generated Generic medications have generated substantial savings in health care substantial savings in health care budgets and helped expand access to budgets and helped expand access to care in several diseases and have a care in several diseases and have a great potential role in the treatment great potential role in the treatment of cancerof cancer

Unsafe medicines are a potential Unsafe medicines are a potential serious problemserious problem

Hope for the futureHope for the future

Patient selection will improve and enable Patient selection will improve and enable us to choose therapies with greater us to choose therapies with greater efficacy and safetyefficacy and safety

Better selection and fewer adverse events Better selection and fewer adverse events will make cancer care more cost-efficientwill make cancer care more cost-efficient

This will be achieved with an increase in This will be achieved with an increase in funding for translational and clinical funding for translational and clinical researchresearch

Hope for the FutureHope for the Future

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

How to do it!How to do it!

It will take the whole world to control It will take the whole world to control cancer in low and middle income cancer in low and middle income countriescountries

How to do it!How to do it!

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

How to do it!How to do it!

Join the fight!Join the fight!

““Strive not to be a success, Strive not to be a success, but rather to be of value” but rather to be of value”

Albert EinsteinAlbert Einstein