Deadly Imbalance: Deadly Imbalance: Social vs Medical Social vs Medical

Value of Preventative Value of Preventative VaccinesVaccines

Donald P. Francis, MD, DScDonald P. Francis, MD, DSc

Global Solutions for Infectious DiseasesGlobal Solutions for Infectious Diseases

Brisbane, CA, USABrisbane, CA, USA

Public Health GoalPublic Health Goal

Decrease or eliminate diseaseDecrease or eliminate disease

Public Health GoalPublic Health Goal

Decrease or eliminate diseaseDecrease or eliminate disease

……....in the shortest time in the shortest time possiblepossible

OutlineOutline1.1. Delayed disease control - Delayed disease control -

examplesexamples

2.2. Why? Lack of social valueWhy? Lack of social value

3.3. Roles of industry and public Roles of industry and public healthhealth

4.4. Costs of vaccine Costs of vaccine developmentdevelopment

5.5. Costs of delayed vaccine Costs of delayed vaccine useuse

6.6. Positive changes: “push” Positive changes: “push” and “pull”and “pull”

0

Mor

talit

y ra

te p

er 1

00,0

00/y

ear

DiptheriaPertussisMeaslesPoliomyelitisAIDS

Year1900 1920 1940 1960 1980

10

20

30

40

Infectious Disease Mortality Rates in the U.S.

SmallpoxSmallpox

Vaccinia (smallpox) Vaccine

1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 19770

5

10

15

20

25

30

35

40

Years

Num

ber

of c

ount

ries

(Smallpox and Its Eradication, WHO, 1998, pg517-38)

Number of Countries with Smallpox1967 - 1977

The Tragic DelayThe Tragic DelayVaccine CommerciallyVaccine Commercially Eradicated:Eradicated:

AvailableAvailable North Am/EuropeNorth Am/EuropeWorldwideWorldwide

SmallpoxSmallpox ~1900 ~1900 1930-1953 1930-1953 1967-771967-77

DelayDelay 30 to 53 years30 to 53 years 67-77 years 67-77 years

PolioPolio

Iron Iron LungsLungs

Rancho Rancho Los Los

Amigos, Amigos, CACA

PresidePresident nt

FrankliFranklin n

RooseveRooseveltlt

(1882-(1882-1945)1945)

Polio at Polio at age 39age 39

cccc

cccc

PolioBihar, India 2005

cccc

cccc

Dr. Jonas Salk

Vaccine licensed in 1955

cccc

cccc

NID – National Immunization Day

1998 1999 2000 2001 2002 2003

Monthly incidence of polio in IndiaJanuary 1998 – December 2005*

2004

SNID – Sub-National Immunization Day Large scale mop-up

2005

Number of cases

NID NID NID NID NID NIDSNID SNID SNID SNID SNID NID Mop-upNIDSNID NID SNIDSNID SNID

* data as on 3rd March, 2006

The Tragic DelayThe Tragic DelayVaccine CommerciallyVaccine Commercially

Eradicated:Eradicated:AvailableAvailable North Am/EuropeNorth Am/Europe

WorldwideWorldwide

SmallpoxSmallpox ~1900 ~1900 1930-1953 1930-1953 1967-771967-77

DelayDelay 30 to 53 years30 to 53 years 67-77 years 67-77 years

PolioPolio 19551955 1991 1991>2005>2005

DelayDelay 36 years 36 years >50 >50 yearsyears

Hepatitis BHepatitis B

Hepatitis B - Clinical Features

Hepatitis B - Clinical Features

• Incubation period: Average 60-90 daysRange 45-180 days

• Clinical illness (jaundice): <5 yrs, <10%5 yrs, 30%-50%

• Acute case-fatality rate: 0.5%-1%

• Chronic infection: <5 yrs, 30%-90%5 yrs, 2%-10%

• Premature mortality fromchronic liver disease: 15%-25%

Vaccinelicensed

HBsAg screening

of pregnant women

recommended

Infantimmunizationrecommended

OSHA Ruleenacted

Adolescent immunization recommended

*Decline among

homosexual men & HCWs

Decline among

injectingdrug users

80

70

60

50

40

30

20

10

0

78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95

Year

Ca

ses

per

10

0,0

00 P

op

ula

tio

n

* Provisional date

Estimated Cases of Hepatitis B1978 – 1995

USA

Why?Why?

Social Value Drives Social Value Drives Vaccine Development Vaccine Development

and Applicationand Application

Scientific DiscoveryScientific Discovery

Vaccine DevelopmentVaccine DevelopmentSocial ValueSocial Value

Vaccine ApplicationVaccine Application

Expertise to Expertise to Develop VaccinesDevelop Vaccines

• Public/university institutes Public/university institutes • Private pharmaceutical Private pharmaceutical companiescompanies

Academic Academic ResearchResearch versus Pharmaceutical versus Pharmaceutical

DevelopmentDevelopment““The public sector institutions involved in vaccine The public sector institutions involved in vaccine R&D are primarily focused on basic science R&D are primarily focused on basic science knowledge diffusion, rather than single-mindedly knowledge diffusion, rather than single-mindedly solving applied development problems to ensure solving applied development problems to ensure large scale, consistent production. The incentives large scale, consistent production. The incentives in the public sector reinforce this knowledge focus in the public sector reinforce this knowledge focus and are generally inconsistent with efficient and are generally inconsistent with efficient production of commodities.“production of commodities.“

McKinsey & Company. Preliminary Report. How can McKinsey & Company. Preliminary Report. How can public-private partnerships accelerate the availability of public-private partnerships accelerate the availability of vaccines for the developing world? July 2001. World vaccines for the developing world? July 2001. World BankBank

Output Output Measurements of Measurements of

Each PlayerEach Player

PlayerPlayer Output Output MeasurementMeasurement

Public InstitutesPublic Institutes Knowledge/ManuscriptsKnowledge/Manuscripts

Private CompaniesPrivate Companies Products and Products and ProfitsProfits

Social Value Drives Social Value Drives Vaccine Development Vaccine Development

and Applicationand Application

Scientific DiscoveryScientific Discovery

Vaccine DevelopmentVaccine DevelopmentSocial ValueSocial Value

Vaccine ApplicationVaccine Application

Low Value Given to Low Value Given to

Vaccines:Vaccines:

• By vaccine industry - who makes By vaccine industry - who makes vaccinesvaccines• By public health (society) - who By public health (society) - who uses vaccinesuses vaccines

Public Health’s Role in Public Health’s Role in Discouraging Vaccine Discouraging Vaccine

DevelopmentDevelopment

• Recognize value, but unwilling to pay Recognize value, but unwilling to pay for vaccinesfor vaccines• Little or no urgency to deliver new Little or no urgency to deliver new vaccinesvaccines

The global vaccine market

Developing countriesIndustrialized countries

Population

Disease Burden

Vaccine market

18%82%

93%

85%

T=$6 Billion/y

15%

7%

Vaccine R&D

T= $500 Million/y90% 10%

Pricing in Low vs. High Pricing in Low vs. High Income CountriesIncome Countries

Primary Disease compared to

vaccineMeasles

Diptheria, Pertussis, Tetanus

TB HepatitisBHaemo

philious BPolio

Low Income Countries

Measlesmomoin

combo with DTp

Middle Income Countries

MMRwholecell in combo

BCGin combo

with DTPwin combo

with DTPwOPV

High Income Countries

14c

$15.50

7c

$10.65

10c

$8.25

7c 32-90c

$9.00

$3.10

$21.38

Cape Town, RSA April 11, 2002

““Low or uncertain demand for new vaccines in Low or uncertain demand for new vaccines in developing countries, together with the low developing countries, together with the low prices negotiated over the years for the prices negotiated over the years for the traditional six vaccines (DPT, polio, measles traditional six vaccines (DPT, polio, measles and BCG) for use in developing countries, and BCG) for use in developing countries, have deterred vaccine manufacturers from have deterred vaccine manufacturers from developing vaccines for use almost exclusively developing vaccines for use almost exclusively in what are perceived to be “low profit” in what are perceived to be “low profit” countries.” countries.”

(WHO, State of the World’s Vaccines and (WHO, State of the World’s Vaccines and Immunization, 2002)Immunization, 2002)

Vaccine development is Vaccine development is expensive.expensive.

Vaccine Development CostsVaccine Development CostsLicensed Product: Flumist Licensed Product: Flumist

ExampleExample

InvestmentInvestment

1996 – 20021996 – 2002 Research & DevResearch & Dev$145mm$145mm

2003 – 20042003 – 2004 Manufacture and LicenseManufacture and License$200mm$200mm

Source: H. Greenberg (2004)Source: H. Greenberg (2004)

Investment Investment Required to Required to Develop One Develop One

VaccineVaccine

Money: Money: $200 to $200 to $500mm$500mm

Time:Time: 12 to 15 years12 to 15 years

Why Vaccines Fail to Why Vaccines Fail to CompeteCompeteVaccine/Therapeutic Market ComparisonVaccine/Therapeutic Market Comparison

Lipitor = atorvastatin calciumPrilosec = omepraxole

Source: Piers Whitehead: Vaccine market data 2000, pharma sales 2001

Costly ResultCostly Result

Lack of social valueLack of social value

Lack of political (government) Lack of political (government) leadershipleadership

CostlyCostly

Costs of Vaccine Costs of Vaccine DelayDelay

• Continued disease occurrenceContinued disease occurrence

Costs of Vaccine Costs of Vaccine DelayDelay

• Continued disease occurrenceContinued disease occurrence• Increased infected pool – more Increased infected pool – more difficult to difficult to controlcontrol

Costs of Vaccine Costs of Vaccine DelayDelay

• Continued disease occurrenceContinued disease occurrence• Increased infected pool – more Increased infected pool – more difficult to controldifficult to control

• Small market further reduces Small market further reduces incentives for incentives for industry to make industry to make vaccines –> more delayvaccines –> more delay

Adjusting market forces.Adjusting market forces.

Altering the Altering the Market FailureMarket Failure

• PushPush• PullPull

Push: Public Push: Public Private Private

Partnerships in the Partnerships in the PastPast

Pasteur InstitutePasteur Institute

diphtheria, TB, pertussis, diphtheria, TB, pertussis, tetanustetanus

Rockefeller FoundationRockefeller Foundation

yellow feveryellow fever

March of Dimes FoundationMarch of Dimes Foundation

poliopolio

Push: Recent Public-Push: Recent Public-Private Partnerships Private Partnerships

for Vaccinesfor VaccinesAeras Global Tuberculosis Vaccine Foundation Aeras Global Tuberculosis Vaccine Foundation (Aeras)(Aeras)European Malaria Vaccine Initiative (EMVI)European Malaria Vaccine Initiative (EMVI)Global Solutions for Infectious Diseases (GSID)Global Solutions for Infectious Diseases (GSID)Human Hookworm Vaccine Initiative (HHVI)Human Hookworm Vaccine Initiative (HHVI)International AIDS Vaccine Initiative (IAVI)International AIDS Vaccine Initiative (IAVI)Malaria Vaccine Initiative (MVI)Malaria Vaccine Initiative (MVI)Pediatric Dengue Vaccine Initiative (PDVI)Pediatric Dengue Vaccine Initiative (PDVI)Pneumococcal Vaccine ADIPPneumococcal Vaccine ADIPRotavirus Vaccine ADIPRotavirus Vaccine ADIPSouth African AIDS Vaccine Initiative (SAVI)South African AIDS Vaccine Initiative (SAVI)

Pull:Pull: Vaccine Purchase Vaccine Purchase FundsFunds

• State and National State and National GovernmentsGovernments• International OrganizationsInternational Organizations

Summary: Adverse Summary: Adverse FactorsFactors

Vaccine development, like other pharmaceutical Vaccine development, like other pharmaceutical development, is costly ranging from $200 to $500 development, is costly ranging from $200 to $500 million per vaccine;million per vaccine;

Vaccine development is slow taking 12 to 15 years;Vaccine development is slow taking 12 to 15 years;The skills necessary to develop vaccines rest The skills necessary to develop vaccines rest

primarily within the private sector;primarily within the private sector;For the same cost and effort, pharmaceutical For the same cost and effort, pharmaceutical

companies can develop therapeutic drugs that companies can develop therapeutic drugs that are far more profitable;are far more profitable;

Public health leaders are cheap and unwilling to pay Public health leaders are cheap and unwilling to pay reasonable prices for valuable vaccines;reasonable prices for valuable vaccines;

The lack of social value given to vaccines makes them The lack of social value given to vaccines makes them unattractive products for the pharmaceutical unattractive products for the pharmaceutical industry to develop;industry to develop;

Vaccines, once developed, are often applied very Vaccines, once developed, are often applied very slowly;slowly;

Summary: Positive Summary: Positive ChangesChanges

Public-private vaccine development Public-private vaccine development partnerships, having pharmaceutical partnerships, having pharmaceutical development expertise, are being development expertise, are being established;established;

Funding is being provided, most notably by Funding is being provided, most notably by the Bill and Melinda Gates Foundation;the Bill and Melinda Gates Foundation;

Foundation support is driving public health Foundation support is driving public health authorities to deliver existing vaccines;authorities to deliver existing vaccines;