Current status, Challenges, and Opportunities Rodney Carbis Head Vaccine Development International Vaccine I nstitute The V accine Business BioMalaysia, 2011 Conference Kuala Lumpur, Malaysia November 21 – 23, 2011
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Current status, Challenges, and Opportunities
Rodney Carbis
Head Vaccine Development
International Vaccine Institute
The Vaccine Business
BioMalaysia, 2011 Conference
Kuala Lumpur, MalaysiaNovember 21 – 23, 2011
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International Vaccine InstituteMission
To promote the health of people in developing countries by thedevelopment, introduction and use of new and improved vaccines”
- From: Const i tu t ion o f IVI (1996)
Disease surveillance
Vaccine introduction
and Advocacy
Vaccinedemonstration
projects
Clinical trials
Vaccine developmentTechnology Transfer
Oral inactivatedCholera vaccine
Typhoid andparatyphoid
conjugate vaccines
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The Value of Vaccines
Ali Maouw Maalin,last case of smallpox
(Somalia,1977)
3
Luis Fermín Tenorio,the last polio case in the
Americas(Peru, 1991)
Vaccines are the most cost-effective toolsfor preventing death and disability frominfectious disease.
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Contrast between Vaccines and other Pharmaceuticals
Vaccines Pharmaceuticals
Focus on prevention
– not patients, but healthy people
Key role for the government agencies
Very low acceptance of side effects
Large clinical trials
5,000 to 10,000 subjects before registration
(67,000 for Wyeth’s Rotavirus vaccine)
Focus on treatment
– patient is generally sick
Key role for the doctors and pharmacists
Acceptance of side effects varies with
severity of disease
Less demanding clinical trials
2000 to 3000 subjects before registration
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Contrast between Vaccines and other Pharmaceuticals
Vaccines Pharmaceuticals
High manufacturing complexity
Biological processes are difficult to
control
Supply chain complexity generally require
storage at or below 4oC
Medium manufacturing complexity
Easier to manage chemical synthesis in
most cases
Supply chain less complex, many drugs
stored at room temperature
Very few generic products
(Due to manufacturing complexity)
Increasing generic threat
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World Vaccine Market
Therapeutic vaccines segment:Cancer vaccines market>US$8 billion by 2012.
No growth for EPI vaccinescontinue to since year 2003.
World Vaccines Market 2008-2013 Future Forecast,Critical Trends and Developments.
US$ 21.05 Billion in 2010 at rate of 8-9 %.Emerging markets growing at 16-17 %.Rise in adult vaccines.Increased uptake of hepatitis and influenza vaccines.
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Three market segments
Market Type Clients Geographical areas Market organization
Commercial MarketBiggest markets invalue by far
Public or private Mainly for developedcountries
Strongly regulatedmarket wherecompetition exists.
Donor MarketBiggest markets indoses but low invalue
Managed byInternationalorganizations suchas WHO, UNICEF,PAHO and GAVI**
Poor or developingcountries
Mostly EPI vaccines forroutine or massimmunization
Closed market Local clients e.g. India, Indonesia,
China, Brazil, Cuba
Local producers supply
the local needs withEPI* vaccines
*Expanded program on immunization (EPI)**World Health Organization (WHO), United Nations Children’s Fund (UNICEF), Pan American Health Organization (PAHO),
Global Alliance for Vaccines and Immunization (GAVI).
Source: Bionest Partners, Exane BNP Paribas
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Value and volume of vaccines2003-2004
0.71.6
11.4
13.7
0
2
4
6
8
10
12
14
16
Poor Middle Rich Total
b i l
l i o n
U S $
Countries
Value of vaccines US$
3.1
1.7
0.8
5.6
0
1
2
3
4
5
6
Poor Middle Rich Total
b i l l i o n
d o s e s
Countries
Number of doses
Most money is made in the rich countries(high profit relatively low number of doses)
Most vaccines are delivered to poor and middle income countries(low profit high number of doses)
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Supply to UNICEFWHO prequalification
Most vaccines for national immunization programs in developing countries are acquired through procurement by UNICEF.
Vaccines must be prequalified by the WHO to be considered in these tenders.
Prequalification involves the National Regulatory Authority as well as the manufacturing company. Prequalification isspecific to a certain vaccine produced by a certain company. It does not mean that the company can apply for tender for allits products only those that are prequalified.
How important is prequalification:
Manufacturers ofPentavalent vaccine
CountryPrequalified
productVolume/value on theInternational market
Bharat Biotech India No
Panacea Biotech India YesUS$34.2M to UNICEF: >15Mdoses
Shantha Biotechnics India Yes US$340M contract with UNICEFfor 2010-2012
Berna Biotech/CrucellRepublic of
KoreaYes
In 2008, supplied >29M dosesthrough UNICEF/GAVI
Serum Institute India No
Biological E India No
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Increasing contribution from emergingmarkets
Source: UNICEF Supply Division, 2011
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Continuing contraction of the vaccineindustry
Big Pharma showing more interest in vaccines and taking positions indeveloping country manufacturers:
$68 billion acquisition of Wyeth, Pfizer is now in the vaccine business
Abbott Laboratories spent $6.6 billion to purchase flu vaccine maker Solvay
Johnson & Johnson bought 18 percent of Dutch vaccine manufacturer Crucell
GSK signed a $78 million joint venture with China's Shenzhen NeptunusInterlong Bio-Technique
Sanofi acquired a majority stake in Indian vaccine maker Shantha Biotechnics,
Novartis spent $125 million for an 85 percent stake in privately ownedChinese vaccines company Zhejiang Tianyuan
Source: Spiegel Online –Germany-
Author: By Kerry Capell Titel: The Vaccine Renaissanc e ; Published:November 25th 2009
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Blockbusters in 2008Sales greater than 1 billion US$
Vaccines approved in last five years have created new markets. Theseleading products in 2008 totaled to US$10 billion
Worldwide markets more than doubled in last three years. It is forecasted thatsales will double again to US$50.7 billion by 2013.
Product Company Sales US$
Prevnar Wyeth 2.7 billion
Gardasil Merck 1.4 billion
Proquad/Varivax Merck 1.3 billion
Infantrix GSK 1.3 billionPolio/whoopingcough/Hib vaccines
Sanofi Pasteur 1.1 billion
Influenza Sanofi Pasteur 1.1 billion
Hepatitis Vaccines GSK 1.2 billion
www. pipeline review. com . LaMerie Biologic Report Recommendation: The new vaccines
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Vaccine Development1910-2010
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List of vaccine preventable diseases
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TrendsCombination vaccines
3 valent DTwP
4 valent DTwP-Hep B5 valent DTwP-Hep B-Hib6 valent DTaP-Hep B-Hib-IPV
Measles combination vaccine1 valent Measles3 valent Measles/Mumps/Rubella
To reduce the number of vaccinations children receivevaccines are increasingly becoming multivalent.
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TrendsMultivalent vaccines
Protect against more strains.Differentiation of one companies product from another to gainmarket advantage.
Rotavirus
Rotarix (GSK) 1 strain G1[P8]Rota Teq (Merck) 5 strains G1,G2, G3, G4, [P7, P1A]
HPVGardasil (Merck) types 16, 18, 6 and 11Cervarix (GSK) types 16 and 18
Pnuemococcal conjugatePrevnar (Wyeth now Pfizer) - (originally 7 valent)Prevnar 13 (Wyeth now Pfizer) - (now 13 valent)
Synflorix (GSK) contains 10 strains
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TrendsSafety
Oral Live attenuated polio vaccine (OPV) has been replaced by the inactivatedpolio (IPV) in industrialized countries. Issues with reversion to virulence withone of the three strains in the OPV
Whole cell pertussis (wP) which is reactogenic has been replaced with acellular pertussis (aP) in industrialized countries. Currently aP is too expensive forroutine use in developing countries.
Single use auto-disable syringes so that syringes cannot be reused.
Preservatives such as thiomersal being excluded from formulations (particularlysingle dose presentations)
Increased emphasis on safety
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TrendsManufacturing
Stronger emphasis on Validation
Use of single use technologies hassimplified validation.
Single use technologies are easier toinstall and facilitate earlier time tomarket than conventional equipment
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ChallengescGMP compliance
Vaccine manufacturers must comply with current Good Manufacturing Practice(GMP), keeping track of the latest guidelines is time consuming and difficult.
cGMP is a part of the quality system used in the manufacturing, testing anddevelopment of vaccines
Companies who fail inspections can expect to facepenalties. Fines and product bans are common butoften most damaging is the loss of consumerconfidence in the product.
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ChallengesLimited manufacturing capacity
Very little surge capacity as redundant capacity is costly, long timelines torespond to increased demand.
For many vaccines there are only one or two producers.
Demand for pediatric vaccines is predictable and is related to the birth cohort.
Lack of capacity creates vulnerabilities should demand suddenly increase suchas occurred during the 2009-10 H1N1 outbreak.
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Challenges
As disease is controlled by vaccination the need for vaccination is less obvious.
Pressure from anti vaccine groups can also reduce vaccine acceptance andcoverage.
Complacency can lead to re-emergence of disease as occurred in Russia in the1990s
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Adjuvants
Aluminum salts were first used in the 1920s.New adjuvants introduced in the last decade.
An immunologic adjuvant acts to accelerate, prolong,or enhance antigen-specific immune responses whenused in combination with specific vaccine antigens
AdjuvantName
Class Company Indications Status
Alum Mineral salts Various Various Marketed (EU, USA)
MF59® Oil-in-water emulsion Novartis Influenza Marketed (EU)
AS03 Oil-in-water emulsion GSK Influenza Marketed (EU)
AS04 Alum + TLR4 antagonist GSKHepatitis B, human
papillomavirusMarketed (EU, USA)
AS01 Liposome, MPL, QS-21 GSK Malaria Phase 3
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Stabilization
Storage of vaccines is costly, generally require refrigeration
Experience with monovalent H1N1 vaccine for the 2009/2010 season.
Significant losses due to expiry of product.- US: 71 out of 162 million doses.
- Australia: 9.7 out of 19 million doses.
Vaccine recall due to inadequate stability.- 13 lots of live attenuated H1N1 influenza.
- One lot split H1N1 pediatric vaccine (800,000 doses).
Substantial amount of work being doneon developing more stable formulationsto reduce product loss and reduce thedependence on the cold chain
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FuturePhase III vaccines in development
Disease Company Drug NameSmoking addiction Nabi Biopharmaceuticals NicVAX
Grass Allery ALB Abello GRAZAX
Grass Allery Allergy Therapeutics Pollinex Quattro Grasses
Ragweed Allergy Allergy Therapeutics Pollinex Quattro Ragweed
Grass Allery Fornix Biosciences Oralgen Grass Pollen
Grass Allery Greer Labs Sublingual-oral immuno-therapy
Grass Allery Paladin Labs Oralair Grasses
Pollen Allergy Schering-Plough/Merck Allergy Immunotherapy Tablet
Dengue Sanofi Pasteur ChimeriVax
Diabetes Diamyd Medical DiamydETEC infection Intercell Traveler's Diarrhea vaccine patch
Herpes virus GlaxoSmithKline Simplirix
Leishmaniasis Tehran University of Medical Sciences Alum-ALM
Malaria GlaxoSmithKline Mosqurix
Shigellosis NICHHD, NIH N/A
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Other interesting disease targetsVaccines currently in phase II trials
Disease Clinical development phase
Alzheimer's Phase II
Ebola Phase II
Hepatitis C Phase II
Hypertension Phase II
HIV/AIDS Various phases
MRSA(Methicillin-resistant Staphylococcus aureus)
Phase II
Multiple Sclerosis Phase II
Obesity Preclinical
Cancer Many in various stages of development
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Thank you