Economics of Vaccine Development A Vaccine Manufacturer s Perspective Gerald Voss
The Value of Vaccines 2
29 diseases are currently preventable by vaccination Global public health Cervical cancer 1 Diphtheria 1 Haemophilus influenzae type b 1 Hepatitis A 1 Hepatitis B 1 Herpes zoster 1 Human papillomavirus 1 Influenza 1 Measles 1 Meningococcal 1 Mumps 1 H1N1 flu 1 Pertussis 1 Poliomyelitis 1 Pneumococcal 1 Rotavirus 1 Rubella 1 Smallpox and vaccinia 1 Tetanus 1 Tuberculosis 1 Varicella 1 Vaccines are one of the greatest achievements of biomedical science and public health Regional focus Anthrax 1 Cholera 2 Japanese encephalitis 1 Monkeypox 1 Tick-borne encephalitis 3 Typhoid fever 1 Rabies 1 Yellow fever 1 1. Centers for Disease Control and Prevention (CDC). Vaccines and preventable diseases. Available at: www.cdc.gov/vaccines/vpdvac/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)
Making the case for vaccines Vaccines are important tools to combat infectious diseases globally and have proved to reduce mortality and morbidity caused by several pathogens 4
Polio distribution before mass vaccination 1988: before the Global Polio Eradication Initiative Endemic Non-endemic In 1988, polio was endemic in 125 countries 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)
Polio distribution after mass vaccination 2013: Endemic Non-endemic In 2013, polio remains endemic in 3 countries WHO. Global Polio eradication initiative. Available at: http://www.polioeradication.org/dataandmonitoring/poliothisweek/poliocasesworldwide.aspx (accessed August 2013);
Making the case for vaccines Vaccines are important tools to combat infectious diseases globally and have proved to reduce mortality and morbidity caused by several pathogens 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. Market size has increased from 5 bn in 2000 to 24 bn US $ in 2013 1 Every year up to 3 million deaths are prevented and 750,000 children are saved from disabilities through vaccination 2 GSK s contribution For over 50 years we have supplied polio vaccines for elimination and eradication efforts worldwide 3 In 2010, we delivered 1.4 billion vaccines doses to 179 countries worldwide 4 Up to 70% of our volumes are distributed in low and middle income countries 4 GSK has a tiered pricing policy to enable pricing to be aligned to a country s ability to pay 4 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 8 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 several pathogens 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 saved 1 Savings from the Global Polio Eradication Initiative is expected to reach 40-50 billion USD over 1988-2035 period 2 Average Cost per Death Averted and Cost per DALY for the Traditional Immunization Program by Region 3 In 2001 US$ Estimated cost/death averted Estimated cost/daly East Asia and the Pacific Europe and Central Asia Latin America and the Caribbean Middle East and North Africa South Asia Sub- Saharan Africa 434 3,540 1,030 993 205 205 85 395 438 166 16 7 1 CDC MMWR 1999/48(12); 243-248 2 Tebbens, Vaccine, 2011 3 Jamison, World Bank, 2006 10
Economic rationale for new vaccine development 11
Economic rationale for vaccine development Development risk (and upfront investment) Scientific concept Technical approach Clinical development Regulatory landscape Development risk Potential return Medical need Potential return 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 recommendations 14
Vaccine development challenges 15
Vaccine development is a complex multistep process requiring significant time and financial investment 5-15y 5-15y >>10Y Medical need Pre-clinical assessment Clinical assessment Approval/licensing /post licensure Technical feasibility IND/regulatory submission Regulatory submission/filing Up to 1 bn $ Leroux-Roels et al. Chapter 5 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p115 150
Scientific challenges and innovation challenges Pathogens or diseases malaria, HIV, TB, CMV etc. Populations infants, elderly, immuno-compromised etc. strategies New Antigens New antigen presentation (DNA) New Delivery strategies (live vectors) New Adjuvants Innovation CMV = Cytomegalovirus; HIV = Human Immunodeficiency Virus; TB = Tuberculosis Garçon N, et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam: Elsevier; 2011; chapter 6: p151-199
Technical complexity Vaccine production: bulk manufacturing Making/releasing a vaccine lot can take up to one year Cell culture is used to grow viruses and bacterial media to grow bacteria Pathogens (virus, bacteria) Whole pathogens, split antigens or recombinant proteins are recovered from culture media or expression systems Whole pathogens (inactivated or live attenuated) Courtesy of GSK Expression systems are used to express recombinant proteins Purification Sterile filtration Aseptic manufacturing Batch release Split antigens Subunit vaccine Courtesy of GSK Recombinant proteins Quality control is key at every step of the vaccine manufacturing process Leroux-Roels et al. Chapter 5 in: Garçon et al. Understanding Modern Vaccines, Perspectives in Vaccinology, Vol 1, Amsterdam, Elsevier, 2011, pp. 115 50
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 very challenging to execute well Phase IIIb/IV programs including significant post-licensure commitments 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 development sustainable Reward innovation Define future public health needs (elderly populations,.) Product Development Partnerships for Diseases of the Developing World Create broad alliances for implementation
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