Economics of Vaccine Development

A Vaccine Manufacturer’sPerspective

Gerald Voss

2

The Value of Vaccines

29 diseases are currently preventable by vaccination

‘Vaccines are one of the greatest achievements of biomedical science and

public health’

1. Centers for Disease Control and Prevention (CDC). Vaccines and preventable diseases. Available at: www.cdc.gov/vaccines/vpd-vac/default.htm (accessed August 2013); 2. Roush et al. MMWR 1999;48:243–8; 3.CDC. Special pathogens branch. Available at: www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/TBE.htm (accessed August 2013)

Anthrax 1

Cholera 2

Japanese encephalitis 1

Rabies 1

Tick-borne encephalitis 3

Typhoid fever 1

Yellow fever 1

Monkeypox 1

Diphtheria 1

Haemophilus influenzae type b 1

Hepatitis A 1

Hepatitis B 1

Measles 1

Meningococcal 1

Mumps 1

Pertussis 1

Pneumococcal 1Poliomyelitis 1

Rubella 1

Smallpox and vaccinia 1

Tetanus 1

Tuberculosis 1

Varicella 1

Human papillomavirus 1

Influenza 1

Rotavirus 1

Herpes zoster 1

Cervical cancer 1

H1N1 flu 1

Global public health Regional focus

Making the case for vaccines

• Vaccines are important tools to combat infectious diseases globally and have proved to reduce mortality and morbidity caused by severalpathogens

4

Polio distribution before mass vaccination1988: before the Global Polio Eradication Initiativ e

Endemic

Non-endemic

WHO. Global Polio eradication initiative. Available at: http://www.polioeradication.org/Polioandprevention/Historyofpolio.aspx (accessed August 2013); WHO Global eradication of polio: the case for “finishing the job” http://www.who.int/bulletin/volumes/85/6/06-037457/en/ (accessed August 2013)

In 1988, polio was endemic in 125 countries

Polio distribution after mass vaccination2013:

WHO. Global Polio eradication initiative. Available at: http://www.polioeradication.org/Dataandmonitoring/Poliothisweek/Poliocasesworldwide.aspx (accessed August 2013);

Endemic

Non-endemic

In 2013, polio remains endemic in 3 countries

Making the case for vaccines

• Vaccines are important tools to combat infectious diseases globally and have proved to reduce mortality and morbidity caused by severalpathogens

• We manufacture vaccines and provide access for all to existing and new vaccines that are:

– Immunogenic/efficacious and effective

– Of high quality with an acceptable safety profile

– Affordable

7

Vaccination on a global scale

• Vaccines account for 2-3% of the global pharmaceutical market. Marketsize has increased from 5 bn in 2000 to 24 bn US $ in 20131

• Every year up to 3 million deaths are prevented and 750,000 children are saved from disabilities through vaccination2

• GSK’s contribution

– For over 50 years we have supplied polio vaccines for elimination and eradication efforts worldwide3

– In 2010, we delivered 1.4 billion vaccines doses to 179 countries worldwi de4

– Up to 70% of our volumes are distributed in low and middl e income countries 4

– GSK has a tiered pricing policy to enable pricing to be aligned to a country’s ability to pay4

8

• 1 Kaddar, M. Global Vaccine Market Features and Trends. Global Action plan for Influenza vaccines.• http://who.int/influenza_vaccines_plan/resources/session_10_kaddar.pdf, accessed March 13,2014• 2 Ehreth J. The value of vaccination: a global perspective. Vaccine 2003; 21: 4105-4117• 3 Explore GSK http://www.gsk.com/explore-gsk/health-for-all/polio---rise-and-fall-of-an-endemic-virus.html• 4 GSK Corporate Brochure 2011

Making the case for vaccines

• Vaccines are important tools to combat infectious diseases globally and have proved to reduce mortality and morbidity caused by severalpathogens

• We manufacture vaccines and provide access for all to existing and new vaccines that are:

– Immunogenic/efficacious and effective

– Of high quality with an acceptable safety profile

– Affordable

• Vaccines are highly cost-effective

9

Vaccines are highly cost-effective

• Important savings are generated with polio and measles vaccination– For every dollar spent in those vaccines 6 USD and 13.5 USD of direct and

indirect cost are saved1

– Savings from the Global Polio Eradication Initiative is expected to reach 40-50 billion USD over 1988-2035 period2

• Average Cost per Death Averted and Cost per DALY for the Traditional Immunization Program by Region3

10

In 2001 US$

East Asia and the Pacific

Europe and

Central Asia

Latin America and the

Caribbean

Middle East and

North Africa

South Asia Sub-

Saharan Africa

Estimated cost/death averted

434 3,540 1,030 993 205 205

Estimated cost/DALY

85 395 438 166 16 7

• 1 CDC MMWR 1999/48(12); 243-248• 2 Tebbens, Vaccine, 2011• 3Jamison, World Bank, 2006

11

Economic rationale for new vaccine development

Economic rationale for vaccine development

Potential return

Dev

elop

men

tris

k

• Development risk(and upfront investment)

– Scientific concept

– Technical approach

– Clinical development

– Regulatory landscape

• Potential return – Medical need

– Product properties (including cost of goods)

– Financial return on investment

Overall value proposition

• Individual health– Reduction in morbidity and mortality

• Public health improvement– Control, elimination and eradication

– Herd immunity

• Economic benefit– Direct (healthcare cost)

– Indirect (economic development)

• Societal benefit– Equity

– Human capital

• Developer/manufacturer business model– Financial return on Investment

13

Building a target product profile

• Unmet medical need– Global or regional

– Epidemiology

• Target population– Age (infants, adults, elderly)

– Special populations (immuno-compromized, travellers, maternal immunization)

• Administration– Route

– Schedule (and co-administration)

– Boosters

• Vaccine composition and presentation– Live-attenuated, whole-killed, recombinant, vector

• Implementation– Anticipated standard of care

– Future recommendations14

15

Vaccine development challenges

Vaccine development is a complex multistep process requiring significant time and financial investment

Medical need

Technical feasibility

IND/regulatory submission

Regulatory submission/filing

Pre-clinical assessment

5-15y 5-15y

Clinical assessment

>>10Y

Approval/licensing/post licensure

Leroux-Roels et al. Chapter 5 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p115–150

Up to 1 bn $

Scientific challenges and innovation

Populations

infants, elderly, immuno-compromised

etc.

Pathogens or diseases

malaria, HIV, TB, CMV etc.

New Adjuvants

New Delivery strategies

(live vectors)

New antigen presentation

(DNA)New Antigens

Garçon N, et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam: Elsevier; 2011; chapter 6: p151-199

CMV = Cytomegalovirus; HIV = Human Immunodeficiency Virus; TB = Tuberculosis

chal

leng

esst

rate

gies

Innovation

Technical complexityVaccine production: bulk manufacturingMaking/releasing a vaccine lot can take up to one yea r

Leroux-Roels et al. Chapter 5 in: Garçon et al. Understanding Modern Vaccines, Perspectives in Vaccinology, Vol 1, Amsterdam, Elsevier, 2011, pp. 115–50

Courtesy of GSK

Courtesy of GSK

Cell culture is used to grow viruses and bacterial

media to grow bacteria Pathogens(virus, bacteria)

Expression systems are used to express recombinant proteins

Whole pathogens (inactivated or live attenuated)

Split antigens

Whole pathogens, split antigens or recombinant proteins are recovered from

culture media or expression systems

• Purification• Sterile filtration• Aseptic manufacturing• Batch release

Subunit vaccine

Recombinant proteins

Quality control is key at every step of the vaccine manufacturing process

Quality control is key at every step of the vaccine manufacturing process

Challenges in clinical development

• Clinical development is complex and costly

– Limited utility of preclinical animal models

– First-time-in-human trials have unique challenges – safety first, incremental enrollment, strict holding rules

– Progression to target population (age de-escalation/escalation), robust dose ranging, adjuvant justification, formulation selection increasingly required by regulators

– Proof of Principle (POP) or Proof of Concept (POC) may require human challenge studies or involve complex study designs that approximate Phase III settings

– Phase III programs are often multi-center and multi-country trials and verychallenging to execute well

– Phase IIIb/IV programs including significant post-li censurecommitments add to cost and complexity

19

Regulatory landscape

• Regulatory requirements – are ever increasing (paediatric legislation, post-approval

safety/effectiveness studies, ….), requiring additional investments during vaccine development

– are not entirely aligned between agencies and may differ by region and country, thereby adding complexity to licensure

• Regulatory approval does not mean a vaccine is recommended and reimbursed, and recommendations vary by region and country

20

Conclusions and future perspectives

• Development of new vaccines is becoming ever more demanding and faces multiple challenges that impact the balance between risk and return

There are two levers to meet those challenges:

• Innovation at all levels from Discovery to Implementation– New vaccine technologies

– Improved clinical trial design

– Adapted regulatory pathways

– Delivery science

• Partnerships are needed to render future vaccine developmentsustainable

– Reward innovation

– Define future public health needs (elderly populations,….)

– Product Development Partnerships for Diseases of the Developing World

– Create broad alliances for implementation

Thank you