2015/2016 Year for Vaccine Development

Vasee Moorthy MD PhD

Team Leader

Vaccine Development

§  Established in 2014 to fill strategic gap in our advisory structure - horizon scanning for areas to prioritize WHO attention in pipeline vaccines

§  Three “simple” criteria for attention from WHO: q Unmet public health need focusing on low/middle income

country perspective q Chances of a product emerging from the pipeline

v Probability of technical and regulatory success v Extent of activity/investment in given area

q Added value for WHO engagement in pathogen area

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Product Development for Vaccines Advisory Committee

•  Key endpoints for vaccine evaluation and case definitions through consensus-building on clinical trial progression and design

•  Guiding Target Product Profile (TPP) processes

•  Global R&D Roadmaps including strategic goals to articulate priority unmet public health needs

•  Linking upstream vaccines with surveillance •  Stakeholder consultation •  ?Business case development

Product Development for Vaccines Advisory Committee

Some areas of focus this year

•  A new PHEIC: Zika, TPP development •  MERS-CoV •  Ebola •  RSV •  GBS •  Enterics •  Dengue vaccine licensed •  Malaria vaccine achieves article 58 positive

scientific opinion from EMA

PDVAC: Scanning the pipeline for vaccines

emerging

Regulatory and Policy Perspectives: bridging will optimize public health impact

Regulatory

•  Quality •  Manufacturing consistency •  Safety •  Efficacy, sometimes

inferred from immunogenicity

•  Initial licensure databases for new vaccines have varied from 6,000 to 40,000 or so

•  Risk/Benefit profile

Policy perspective •  Safety •  Efficacy & effectiveness •  Impact, often modelled •  Feasibility of implementation •  Health economic evaluations •  Role of the intervention in the

context of existing interventions

•  Broader perspectives including equity, community acceptability

The pathway from early development to large-scale use: bridging licensure with large scale use

Initial licensure*

Large-scale use

Additional licensure submissions

WHO prequalification WHO policy recommendation

Financing Country interest

*by stringent regulatory authority

577 candidate vaccine

approaches

110 pathogens Pipeline Analyses

List will change each year Emerging pathogens included in 2015

25 pathogens

Pipeline Tracker

2014 …2016…2018

Screening the entire pipeline

Aware of pipeline:

Advising on vaccine

development Strategy & Workplan

Clinical  Development  Manufacturers  

Funding  agencies  

Regulatory  Authori;es  

Ethics  Commi=ees   Principal  

Inves;gators  

Laboratory  Capacity  

Data  Management  

Independent  Oversight  

DSMB,  GCP  monitoring

Ebola  Consor>a  assembled  from  August  2014  

•  What are WHO’s preferences around: – polyvalent vaccines

– duration of protection

– heterologous prime-boost

– stability

2nd gen. Ebola vaccine TPP

Ebola: CVD-Mali Phase 1 results

Lambarene, Gabon

Halifax/PHAC Hamburg Geneva

WRAIR and NIAID

Kilifi, Kenya

Supported by WHO, Newlink, Merck, Public Health Agency of Canada with funds from US Department of Defense, NIAID, BMGF, Wellcome Trust, European Commission

The international partnership facilitating rVSV-ZEBOV Phase 1 evaluation

VSV

17

AVAREF membership: 23 countries which includes Botswana, Burkina Faso, Cameroon, the Central African Republic, Ethiopia, Kenya, The Gambia, Ghana, Gabon, Guinea, Uganda, Tanzania, Mali, Malawi, Mozambique, Niger, Nigeria, Rwanda, Senegal, Sierra Leone, South Africa, Zambia, and Zimbabwe. DCVRN Current membership: Brazil, China, Cuba, India, Iran, Indonesia, Korea, South Africa and Thailand

Regulatory networks to support NRAs

Lessons learned, post Ebola §  Robust pre-clinical model essential cf Zika

§  Comparability of readouts essential for decision-making

§  Pre-existing Phase 1 data could speed timelines by 6 months or more in emergencies

§  Manufacturing and Phase 3 timelines may then become rate limiting step

§  Recombinant protein platforms and recombinant viral vectors validated by Ebola experience

§  Public sector push and pull investment mechanisms in pre-emergency phase are the critical gap now

RTS,S/AS01 : 2 landmarks in 2015

•  July 2015: European Medicine’s Agency provides positive scientific opinion, indicating a favorable assessment of the risk-benefit balance of RTS,S/AS01 from a regulatory perspective

•  October 2015: Two advisory bodies to WHO - the Strategic Advisory Group of Expert on Immunization (SAGE) and the Malaria Policy Advisory Committee (MPAC) – recommend pilot implementation of the vaccine in 3-5 settings

Rationale for pilot implementations recommended by WHO

•  WHO recommends pilot implementations of RTS,S/AS01 to answer outstanding questions before wider scale-up is considered. The pilots should allow: -­‐  Assessment of operational feasibility of providing

malaria vaccine in target age group at the recommended 4-dose schedule in the context of health service delivery.

-­‐  Evaluation of the impact of the vaccine on all cause child mortality when implemented in the setting of concomitant recommended malaria interventions.

-­‐  Surveillance of adverse events following vaccination, with an emphasis on meningitis and cerebral malaria.

•  Developing scientific consensus on development and testing pathways – first IVR consultation on RSV in March 2015

•  RSV surveillance – consultations in 2015 and Feb 2016 (HSE cluster)

•  Regulatory Networks – DCVRN 2015 (EMP/RSS)

•  RSV immunogenicity assays and standard reagents – first consultation Feb 2016 (EMP/ Norms and Standards)

•  First ever review by SAGE 12 April 2016

•  Second IVR RSV consultation late April 2016

Summary of WHO RSV activities

•  SAGE suggested that there is now a critical 4-5 year interval that should be used to systematically identify and fill gaps in evidence required from regulatory, prequalification and policy recommendation perspectives for RSV preventive interventions, including maternal immunization, passive immunization with long-acting monoclonal antibody and paediatric immunization.

RSV - SAGE recommendations

•  About 60 attendees, including research groups, industry, regulatory agencies, funding partners

•  Background, key epidemiological gaps –  Important body of evidence missing: GBS-related stillbirth & prematurity ;

disease burden in LMIC ; strain dynamics and risk of replacement ; unmet need in HIC. Several ongoing initiatives. Compartmental model/systematic review-based global disease burden estimates awaited towards year end (LSHTM-led)

•  Review of current standards of maternal/infant infection prevention and care in LMIC

•  Current vaccine development status: GSK, Pfizer, Minervax

1st WHO Consultation on GBS Vaccine development 27-28 April 2016

•  Safety requirements: build on ongoing MI initiatives •  Correlate of protection working group

•  Phase 3 design considerations –  Importance of clinical endpoints to support policy decisions. Standardization

of data collection according to pre-defined case definitions. Composite endpoint?

–  Acceptability of trial under local standards of care, considering national/WHO recommendations. Role of local authorities

–  Study site requirements. Importance of baseline data

•  Schedule, timing, co-administration data, impact on selected EPI vaccines TBD

GBS Vaccines - Pathway to licensure

•  Documented consensus-based flexible clinical development pathway and Preferred Product Characteristics

•  Protein based approach: need to bridge historical status of CPS-based strategy

•  From evidence to policy and implementation –  Ongoing modelling and health economical evaluations: value

proposition, cost-effectiveness analyses. Prepare long term financing pathways

–  Role in high income countries ? Contribution to reduce antibiotic use ? –  Health system mindset for coordinated maternal and infant care ;

understand health provider, community, parental perspectives and acceptability. Communication and advocacy needs

•  Need to build stakeholder commitment, a GBS vaccine community

GBS vaccines - Forward view

ETEC, severity scores, trial design

•  ETVAX is a leading candidate (an oral, whole cell inactivated vaccine)

•  As with rotavirus, it is expected to reduce severe diarrhoea

•  Discussions on developing a severity score underway

Norovirus

•  Following PDVAC recommendation, assessment for capability to add Norovirus to rotavirus surveillance network underway

•  Phase 2b proof of concept study in adults to start imminently

Global Vaccine Action Plan

•  Key Strategic framework for action related to the Decade of Vaccines

•  PDVAC will review update on specific R&D indicators, and propose recommendations. Documents to be shared imminently, with final recommendations from PDVAC July 29.

Licensed vaccines and how they relate to product development

•  RTS,S/AS01 received article 58 positive scientific opinion

•  CYD-TDV achieved licensure •  What has the experience with these

vaccines taught us about gaps in the current systems especially for vaccines targeting diseases focusing on low income countries?

Strategic issues highlighted

•  Prospects for vaccines with markets only in low income countries

•  The gap between initial licensure and large-scale use

•  Pathways for new types of product eg long-acting mAbs & vaccines in combination with novel delivery devices

•  What is WHO’s role in vaccine development for emerging infectious diseases?

•  Antimicrobial resistance very high on the policy agenda

Thank you for listening