COVID-19 vaccine development
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COVID-19 vaccine development
October 2020
WHO Target Product Profile for COVID vaccines
Vaccine Characteristic WHO preferred outbreak criteria (partial)
Target population All ages. Suitable for pregnant/lactating women
Safety / Reactogenicity Sufficient to provide highly favourable benefit/risk profile
Protective efficacy At least 70 % efficacy against disease, severe disease or
transmission/shedding
Duration of protection Minimum 1 year
Co-administration Standalone
Dose regimen Single-dose primary series.
Lower frequency (yearly or less) of booster doses
Route of administration Non-parenteral
Product stability & storage Higher storage temperatures and higher thermostability
Pipeline of COVID-19 vaccine candidates by development stage and technology platform Date: 14 October 2020
*
• Exploratory: project has not started with in-vivo testing
• Preclinical: project started to test in-vivo / manufacture CTM but not yet started with testing on human
• Start of clinical phases is defined as first subject dosed 3
Date: 15 October 2020
COVID-19 current vaccine clinical development pipeline
COVAX-funded
Phase II/III and
Phase I Phase I/II Phase II
Phase III
Shenzhen Merck Wantai / U.HK Shenzhen Gamaleya AstraZeneca
GIMI - aAPC TMV-083 LAIV DelNS11 GIMI - LV rAd5, rAd26 3 AZD12225
Viral vectors
ReiThera Vaxart Cansino Janssen
Srl - GRAd-COV2 VXA-CoV2-1 Ad5 2 Ad26.COV2-S6
Walvax Imperial CureVac Moderna
Biotech mRNA saRNA CVnCoV mRNA-1273
RNA
Arcturus Pfizer
ARCT-021 BNT1625
Genexine Inovio
GX-19 INO-4800
DNA
Osaka / Cadila
AnGes - AG0301 ZyCoV-D
VLP Sichuan Vaxine Medigen FBRI SRC SpyBio / SII Anhui Zhifei Novavax
Medicago RBD Covax-19 MVC-CO EpiVacCorona VLP-Spycatcher Recombinant NVX-CoV2373
Protein-
based Covaxx U.Q Clover Finlay Sanofi / GSK
UB-612 SClamp SCB-2019 Soberana 01 Recombinant
Bharat IMB CNBG, Sinovac
BBV 152 CAMS WIBP 4 Biotech
Inactivated
RIBSP CNBG,
QazCovid-in BIBP 4
1 U.HK programme distinct from CEPI-funded programme
2 Cansino has been approved for military use in China
3 Gamaleya (rAd5, rAd26) has been conditionally registered in Russia
4 Emergency use approval in China and UAE
5 Under regulatory rolling review
4
6 Under study Pause
Clinical Data
5
Immunogenicity Moderna - mRNA Novavax protein + matrix M
• Candidate vaccines show
binding antibody
• Varying degrees of virus
neutralization
• Cellular responses Th1
oriented
• Some candidates show
reduced immunogenicity in Janssen – Ad26
elderly
6
Comparison of humoral immunogenicity assays
Oxford/ CanSino Gamelaya Janssen Moderna Pfizer/ Pfizer/ Pfizer / Novavax Sinovac WIBP
AZ Institute BioNTech BioNTech BioNTech
1 2 3
Technology Recombinant adenovirus particles RNA in liquid nanoparticles Protein in Inactivated SARS-CoV-2
adjuvant
Antigen Spike Spike Spike Spike Spike RBD RBD Spike Spike Whole virus Whole virus
SARS-CoV-2 Wuhan-Hu-1 Wuhan-Hu-1 Not reported Wuhan- Wuhan-Hu-1 Wuhan-Hu-1 Wuhan-Hu-1 Wuhan-Hu-1 Wuhan-Hu-1 Wuhan-CN2 Wuhan-
Strain / WIV04 (pre- WIV04
isolate* clinical);
Wuhan-Hu-1
(clinical)**
Assay/ ELISA / ELISA / ELISA / ELISA / ELISA/ Luminex/ Luminex/ Luminex/ ELISA / ELISA / ELISA /
antigen Spike RBD RBD & S1 Spike Spike & RBD RBD RBD S1 Spike RBD whole virus
Neutralizing Live virus and Live virus and Live virus Live virus Live virus and Neo-Green Neo-Green Neo-Green Live virus (CPE) Live virus (CPE) Live virus
antibody assay pseudotyped pseudotyped pseudotyped reporter assay reporter assay reporter assay
modality virus virus virus
Neutralizing Germany Wuhan_IME- Moscow_PMVL Australia/Vic01 Washington- Washington- Washington- Washington- Washington- Not reported Wuhan/
antibody assay BavPat1/2020 BJ1 & Wuhan-1 -1/2020 /2020 1/Seattle & 1/Seattle 1/Seattle 1/Seattle 1/Seattle AMMSO1
strain(s) isolate & Wuhan-1
Wuhan-1
Cell substrate* HEK293, Vero Huh7, 293T Vero Vero-E6 293T Vero Vero Vero Vero Not reported Vero
Reference IH-CS None reported IH-CS IH-CS IH-CS IH-CS IH-CS IH-CS IH-CS None reported None reported
reagents**
Other No reports on ADCC or other functional antibody assays involving Fc receptor engagement
7
* Most cell lines are kidney epithelial cells from AGMs; no reports of airway epithelial cells being used
**IH-CS: ‘in-house’ panel of convalescent sera; note no common panels or reagents used
Implications for data comparability and prioritization ‘wish list’
1. Humoral immunogenicity – all groups reporting data with in-house panels of
convalescent sera
• Must have data with reference material (NIBSC antibody standard)
• For both, binding and neutralizing abs
• Could agree on a global panel of common viral isolates
• Washington-1/Seattle
• Wuhan-1
• Victoria (used in CEPI Centralized Labs)
2. Cellular immunogencity
• ELISPOT – most groups reporting gIFN
• ICS – no uniform comparison of cytokines (TH1 vs TH2)
The Netherlands
UK India
Canada Italy
USA
Bangladesh
8
Summary of Vaccine Safety
• Reactogenicity profile acceptable (in some trials, an increased reactogenicity
was present post 2nd dose)
• No clinically relevant safety signals communicated to date
• Importance of thorough and consistent safety monitoring (some clinical trials
temporarily on hold for routine safety assessments)
• Long(er) term safety F/U in ongoing Ph3 trials important à monitor for
potential vaccine-mediated enhanced disease (VMED)
• Risk management strategy: continue safety surveillance post licensure – align
/ coordinate internationally
9
Efficacy trials - analysis elements
From publicly available efficacy trial protocols
Element Moderna BNT/Pfizer AZ (US trial) Janssen
Primary efficacy First occurrence of COVID-19: Confirmed COVID-19 : First occurrence of COVID-19: First occurrence of COVID-19:
objective/ endpoint a. Positive RT-PCR AND a. Positive RT-PCR or other NAAT# a. Positive RT-PCR a. Positive RT-PCR or other
b. At least 1 of: cough, SOB, or AND b. At least 1 of: Pneumonia (CXR/ molecular test AND
clinical/ radiographic pneumonia b. At least 1 of: fever, cough, SOB, CT); SPO2 ≤ 94% or need for b. Moderate COVID-19 (Any 1 of
OR chills, muscle pain, sore throat, O2; SOB OR RR>20/min; abnormal SpO2 >
c. At least 2 of: fever, chills, myalgia, anosmia/ageusia, diarrhea & c. At least 2 of fever; cough; 93%; pneumonia; DVT; SOB
headache, sore throat, olfactory & vomiting myalgia; fatigue; OR Any 2 of fever, chills/rigors,
taste disorder A 2nd definition with extra symptoms: vomiting/diarrhea*; cough, malaise, headache,
fatigue, headache, congested/runny anosmia/ageusia* myalgia, GI symptoms,
nose & nausea anosmia/aguesia, limb rashes)
OR
c. Severe/critical COVID-19
VE from 14 days post dose 2 onwards 7 days post dose 2 onwards 15 days post dose 2 onwards 14 days post dose 2 onwards
Stratification on Only seronegatives in primary VE 2 primary endpoints – a. without Only seronegatives in primary VE Only seronegatives in efficacy
baseline serostatus analysis; Separate analysis for evidence of past infection & b. analysis; Separate analysis for analysis
seropositives with/without past infection seropositives
Age range Age-based analysis: 18-64 & ≥ 65 16-55 & > 55 (~ 40 % of total Stratified randomisation: 18-55; 56- Stratified enrolment: 18-59 YO & ≥
enrolment [No age-based efficacy 69 & ≥ 70; age-based analysis 60 YO (minimum 30%). Age- based
analysis described] planned, no details analysis secondary
# - nucleic acid amplification test
* - only one finding to be counted toward endpoint definition
10Efficacy trials - analysis elements
From publicly available efficacy trial protocols
Element Moderna BNT/Pfizer AZ (US trial) Janssen
Target VE & LB 95% ≥ 60% & >30% ≥ 60% & >30% ≥ 50% & >30% ≥ 50% & >30%
CI (minimum 5 cases in placebo)
Maximum n (V:P) 30,000 (1:1) 43,998 (1:1) 30,000 (2:1) 60,000 (1:1)
Analysis population • All doses received • All doses received • At least one dose received • Receive study vaccine
for primary endpoint • No significant PDs • No significant PDs • Not seropositive • Seronegative
• No evidence of infection or All-available efficacy: All eligible • Not withdrawn or no COVID-19 • No major protocol deviation
COVID-19 at baseline randomised subjects 1. Received at before Day 15 post dose 2
least 1 dose; 2. Received both doses
VE analysis method Cox-proportional hazard Beta-binomial model Poisson regression model Sequential probability ratio test
No. of IAs planned 2 4 1 Continuous sequential analysis
Cases needed for 151 164 150 154
VE
IAs planned at no. of First: 53 First: 32; Second: 62; First: 75 From 20th event at least once week
cases Second: 106 Third : 92; Fourth: 120 monitoring pre-specified criteria* to
trigger VE analysis
* - First 50% participants 2 months of follow-up; minimum of 6 COVID-19 cases for the ≥60 years; At least 20 cases meeting the primary endpoint definition of moderate to severe/critical COVID-19; at
least 5 cases meeting the primary endpoint definition of severe/critical COVID19
11ACT-ACCELERATOR & COVAX
12Access to
COVID-19 tools
ACCESS
ACCESS TOTO COVID-19
COVID-19 TOOLS
TOOLS (ACT)
(ACT) ACCELERATOR
ACCELERATOR
(ACT) accelerator A Global
A Global Collaboration
Collaboration to Accelerate to
the Accelerate
Development,the Development,
Production Production
and Equitable
COVID-19 diagnostics, therapeutics and vaccines
Equitable Access to New COVID-19 diagnostics, therapeutics and vaccines
and
Access to New
VACCINES
DIAGNOSTICS THERAPEUTICS
(COVAX)
Development &
Manufacturing
Led by CEPI, with industry
CEPI is pursuing a range We are founding partners
of approaches to help of the ACT (Access to Procurement
and delivery at scale
overcome these challenges Covid-19 Tools) accelerator, Led by Gavi
and increase global access a global coalition to
to any future COVID-19 accelerate the development,
Policy and allocation
vaccine production of and equitable Led by WHO
access to new Covid-19
diagnostics, therapeutics Key players
and vaccines
13
SOURCE: (ACT) ACCELERATOR Commitment and Call to Action 24 April 2020
thCOVAX goals
• To develop the largest and most diverse
actively managed portfolio of vaccine
candidates so that the best vaccines are
made available and the world has access to
the best science
• To deliver 2 billion doses by end of
2021
• To guarantee fair and equitable access
to COVID-19 vaccines for every country
in the world
14181 countries have now joined COVAX
World’s largest
Speed premium Equitable access
and most diverse
global procurement based on fair
portfolio of Vx
to share risks allocation
candidates
15Many companies are selling doses to high income countries, risking access for the rest of the world
16
Date: 23 September 2020Manufacturing
To deliver 2 billion doses by the
end of 2021, 2-3 successful
programmes are needed to:
1 Produce early doses to support
clinical studies
2 Scale up processes to industrial
scale before clinical trials begin
3 Scale-out products in different
countries to expand capacity
1
4 Stockpile vaccines in bulk in 7
anticipation of dose level
definition
Anticipate projects failing during
5 clinical development
Repurpose facilities for successful
6 products, if neededConcluding thoughts
• Rapid progress in vaccine development globally
• Multiple efficacy studies ongoing around the world
• Manufacturing at scale and tech transfer just beginning
• Many challenges still to face, especially for low resource settings
• Two doses likely needed for first vaccines
• Data in other populations (children, immunosuppressed, pregnant women)
• Cold chain requirements
• Durability and need for booster vx unknown
• Pharmacovigilance
• Regulatory approvals for use in all countries
• Delivery and introduction
CONCLUSIONS 18
• Promising immunogenicity data for the vaccine portfolioYou can also read
