ev71 vaccine development
TRANSCRIPT
EV71 Vaccine Development
Weining Meng
DCVMN 15th Annual General Meeting
29th October, 2014
A R&D Oriented company
A Nasdaq Listed
Company
An Integrated
Vaccine Company
Sinovac-A leading vaccine company in China
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Our Products: Hepatitis Our Products: Influenza
We are: 1st company to develop inactivated hepatitis A vaccine in China 1st company to develop combined hepatitis A and B vaccine in China 1st company to complete phase I clinical trial on SARS vaccine worldwide 1st company to develop H5N1 vaccine in China 1st company to develop and get license of H1N1 vaccine worldwide
1st and only Chinese vaccine company listed in Nasdaq
Our Mission
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• Provide Chinese Population with International Quality Vaccines
• Provide Vaccines Made in China to Worldwide
Supply Vaccines To Eliminate Human Diseases
Our Products: Hepatitis Our Products: Influenza
Manufacturing Facilities
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Manufacturing Plants
Dalian
Vero Cell Cultured Vaccine and Live Attenuated Vaccine
Capacity:5-20 million
Building Area: 13,500 square meters
Headquarter- Beijing
Beijing
Dalian
Tangshan
Healive production plant
Capacity:10 million
Filling & Packaging Plant
Capacity :20 million
Anflu Production plant
Capacity :8 million
Tangshan
Yi’an Animal Vaccine
Capacity of Filling and Packaging:100 million Capacity of EV71:10-20 million
Changping District, Beijing
Novel Vaccine Production Base
Capacity :6-15 million
R & D Center
Building Area: 29,000 square meters
Building Area: 95,000 square meters
Hand Foot Mouth Disease Epidemic
New Zealand, Hand Foot Mouth Disease was reported and defined
Bulgaria, 705 cases, 44 deaths
Malaysia, 2628 cases, 30 deaths
Taiwan, 129106 cases, 78 deaths
Taiwan, 80677 cases, 41 deaths
US, EV71 was isolated
1969 1957 1975 1997 1998 2000
Mainland of China, Korea, Viet Nan , etc. millions cases reported and thousands dead
2007
EV71 Epidemic In China
2007-August,2014,
In total 11 millions HFMD reported,with more than
3,100 fatal cases
《Hand, foot, and mouth disease in China, 2008–12:An epidemiological study》
EV71 EV71 EV71
Total Serious Death
Mild cases:45% are EV71 Serious cases:80% are EV71 Fatal cases:90% are EV71
Serious HFMD epidemic in China;
EV71 inducing main serious and fatal cases;
Vaccine against EV71 is the answer.
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2007 2008 2009 2010 2011 2012 2013 2014
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500000
1000000
1500000
2000000
2500000
死
亡
数
发
病
数
2007-2014年手足口病报告发病、死亡数统计
发病数 死亡数
Rep
orted
Cases
Fatal Cases
截止8月份
HFMD Reported Cases and Fatal Cases 2007-2014
Reported Cases Fatal Cases
Development Milestones
2013.5 申请生产
Pre-clinical study
IND Application
Clinical study
Industrialization
NDA Application
Characters of Sinovac EV71 Vaccine
Vero Cell, cell factory cultivation technology;
H07 strain, C4 subgenotype, isolated by China CDC;
Inactivation with formaldehyde
Al(OH)3 as adjuvant
100 u/200u/400 u, 2 doses/3 doses regimen
EV71 Vaccine Clinical Trails
Phase I
• Objective:Safety, Immunogenicity
• Subjects:Babies, children, and Adult
• Dose:100U、200U、400U
Phase II
• Objective:Immunogenicity, safety
• Subjects:6-35 months babies
• Dose:100U、200U、400U
168 subjects
540 subjects
广西
Phase III
• Objective:Protective effective
• Subjects:6-35 months babies
• Dose:400U
Phase III
• Objective:consistency
• Subjective:6 months-5 years children
• Dose:400U
10077 subjects
1400 subject
s 江苏
All trials following GCP
No significant difference between vaccine group and placebo group
EV71 Vaccine-Safety
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
90.0%
100.0%
发红 硬结 疼痛 肿胀 瘙痒
7.04% 4.96% 4.93% 2.77% 2.16%
6.94% 5.66% 5.06% 2.76% 2.07%
疫苗组 安慰剂组
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
90.0%
100.0%
发热 腹泻 食欲下降 烦躁 恶心呕吐 疲倦 过敏
36.4%
11.7% 8.5% 7.5% 7.4%
3.3% 1.5%
36.1%
12.0% 8.6% 7.0% 7.4%
3.6% 1.33%
疫苗组 安慰剂组
Local Adverse Reactions Systemic Adverse Reactions 发生率 发生率
Vaccine Placebo Vaccine Placebo
Red Scleroma Pain Swelling Itching Fever Diarrhea Anorexia Irritable Vomit Fatigue Anaphylaxis
Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China, The New England Journal of Medicine, 2014
EV71 Vaccine-Efficacy
Protection rate for EV71 infection: 94.3%
Protection for hospitalized cases and serious cases:100.0%
5
94
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90
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疫苗组 对照组
病例数 病例数
Effectiveness for EV71 Infection
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24
0
10
20
30
40
50
60
70
80
90
100
疫苗组 对照组
Protection rate:100.0%
Effectiveness for hospitalized cases
病例数
Protection rate:94.3%
vaccine Control vaccine Control
Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China, The New England Journal of Medicine, 2014
No. of Cases No. of Cases
EV71 Vaccine-Immunogenicity
56 days after vaccination,Neutralizing antibody positive rate 98.79%、GMT 165.79,
8 months and 14 months after vaccination, high level of antibody
Good immunogenicity and immune persistence.
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160
180
GM
T
对照组
疫苗组
Pre-vaccination
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
90.00%
100.00%
阳性率
对照组
疫苗组
Positive R
ate
Control
Vaccine
Control
Vaccine
Pre-vaccination
Efficacy, Safety, and Immunogenicity of an Enterovirus 71 Vaccine in China, The New England Journal of Medicine, 2014
Production 19000 m2
4F Ready for use
3F QC Labs
EV71 Bulk 20 million does/year
2F Formulation
Filling & Packaging 100 million doses/year
1F Cold Room 1.8 million vials
Utilities
Others
4000 m2
2F Animal Lab
1F Biobank
Office 9000 m2
Industrialization Total :29,021 ㎡
Built-up area:32,322 ㎡