A Critical Juncture: progress in TB vaccine
clinical development
5th Global Forum on TB Vaccines
New Delhi, India
Ann M. Ginsberg, MD, PhD
February 21, 2018
Global Clinical Pipeline
2
Viral Vector
Protein / Adjuvant
Mycobacterial – Whole Cell or Extract
Information on candidates in clinical development is self-reported by vaccine sponsors, coordinated by the Working Group on New TB Vaccines and updated
September 2017
Mycobacterial – Live
ID93 + GLA-SEIDRI, Wellcome Trust
Phase 3Phase 2bPhase 2a
VaccaeTM
Anhui Zhifei Longcom
Ad5 Ag85A
McMaster, CanSino
ChAdOx185A/MVA85A (ID/IM/Aerosol)
U. Oxford
DAR-901
Dartmouth, GHIT
RUTI
Archivel Farma, S.L
H56: IC31
SSI, Valneva, Aeras
H4: IC31Sanofi Pasteur, SSI, Aeras
M72 + AS01E
GSK, Aeras
TB/FLU-04L
RIBSP
Phase 1
VPM 1002
SII, Max Planck, VPM, TBVI
(Phase 2/3)
MTBVAC
Biofabri, TBVI, Zaragoza, Aeras
BCG Revaccination
Target Populations
3
• Infants (healthy)
• Adolescents/Adults
(healthy)
• TB patients
4
Increasing focus on adolescent/adult vaccines:
to stop the cycle of transmission - will prevent the spread of TB
to children as well.
See presentation by R. White (LSHTM)
Therapeutic Indications
5
• Prevention of TB disease
– BCG replacement (infants)
– BCG boost (proximal – infants)
– BCG boost (distal – adol/adults)
• Prevention of recurrent TB
• TB treatment shortening +/or
increased cure rates (adjunct
to treatment)
Key Challenges in TB Vaccine Development
6
• Complicated pathogen and disease
• No known correlate of protection
• Not yet known if animal models are
predictive of human TB/protection
• Multiple vaccine candidates in
clinical development
• Licensure trials long and expensive
• Severely underfunded
Approaches to Streamlining Efficacy Trials
7
• Conduct Proof of Concept
trials in high-risk
populations (see Tait et al)
• Use Phase 2 trials to
establish “meaningful
biological effect” of
vaccine (triaging tool)
Decreasing:
₋ Risk
₋ Cost
₋ Time
Clinical Trial Endpoints
8
Prevention of TB disease (POD)
Prevention of Mtb infection (POI)
Prevention of TB disease recurrence (POR)
9
ID93 + GLA-SE
Ph3 in infants
Phase 3Phase 2Phase 1
VaccaeTMMTBVAC
Ad5 Ag85A
ChAdOx185A/MVA85A
TB/FLU-04L
DAR-901
RUTI
H56: IC31
H4: IC31 and BCG revaccination
VPM 1002
M72 + AS01E
Ph2a S&I - infants
Ph1b/2a S&I - adults
Ph1 – FIH Aerosol; adults
Ph1 - ID/IM/Aerosol; adults
Ph2a S&I – MDR-TB pts
Ph2 – POI in QFT- adolescents (in planning)
Ph2 – POR in adult TB pts post-cure (FPI – April 2018)
Ph2 – POI in QFT- adolescents
Ph2 – POI in QFT- adolescents
Ph3 in TST+ adultsPh2b POD – QFT+ Adults
Ph2 – POR in adol/adult TB pts post-cure
Ph1 – FIH; BCG+ adults
Ph2a S&I - adults
Viral Vector Protein / Adjuvant
Clinical
Trials(Not an exhaustive list)
Mycobacterial – Killed Whole Cell or Extract
Mycobacterial – Live attenuated
Efficacy
trials
M72/AS01E
GSK, Aeras
Anhui Zhifei Longcom: AnHui Zhifei Longcom Biologic Pharmacy Co., Ltd; SSI: Statens Serum Institute; VPM: Vakzine Projekt Management GmbH;
SII : Serum Institute of India
Vaccae TM
Anhui Zhifei Longcom
DAR-901
Dartmouth Medical
School, GHIT
VPM1002
Max Planck, VPM, SII
Completed (April 2017)
Awaiting for resultsPhase III 10000 PPD+ 15-65y Prevention of disease China 2018
Phase II 990 Q- 12-17y Prevention of infection South Africa 1Q2018
Phase IIb 3573 Q+ 18-50y Prevention of disease South Africa, Kenya, Zambia 2Q2018
Phase IIb 650 Q- 13-15y Prevention of infection Tanzania 2018
Phase II/III 2000 TB+ 18-65y Prevention of
recurrence
India 2020
Upcoming Data in TB Vaccine Efficacy Trials
Modified from M-A Demoitie, GSK
PHASE PARTICIPANTS EFFICACY LOCATION RESULTS
H4:IC31/BCG revacc
SP, SSI, Aeras
Presentation of results this session, M. Hatherill
New TB
Vaccines are
Achievable
11
Evidence:
− BCG vaccine provides partial protection; for
longer duration than previously recognized
− QFT/TST reverters
− QFT/TST resisters
− 90% of infected indivs. remain ‘LTBI’
− LTBI is partially protective against disease
➢ Vaccines can improve on natural immunity
(e.g., diptheria, tetanus, pneumococcal
conjugate vaccines)
A Critical
Juncture
12
• Improved animal models
• More diverse pipeline under development
• Progress towards a human challenge model
• Novel Phase 2 trial designs in high risk
populations
• Imminent results from multiple efficacy trials
• Biomarker/signature/correlate discovery
TB Vaccine R&D is Severely Underfunded
13
• Annual global cost of TB ~ $20B ($200B
over next 10 years)1
• Cost to develop one vaccine ~ $1.25B over
10 years2
• 2016 funding for TB vaccine R&D: $79M3
• 2016 funding for HIV vaccine R&D: $733M3
Sources: 1. WHO. Trade, foreign policy, diplomacy and health; Tuberculosis Control; 2. Stop TB Partnership. The Global
Plan to End TB 2016-2020; 3. G-Finder 2017; 3. WHO. Global TB Report 2016;
Now more than ever is the time to ensure TB
vaccine R&D gets the funding it needs.
Recent Major Funders and Aeras R&D Partners
14
Current Clinical Sites and Networks
15
With special thanks to the sites and participants and their families in our clinical trials