Malaria Update - PDVAC · Malaria Update - PDVAC Christian F. Ockenhouse, MD PhD Medical Director,...

C E N T E R F O R VA C C I N E

I N N O VAT I O N A N D A C C E S S

PATH/Gabe Bienczycki

Malaria Update - PDVAC

Christian F. Ockenhouse, MD PhD

Medical Director, PATH Malaria Vaccine Initiative

June 27, 2018

C E N T E R F O R V A C C I N E I N N O V A T I O N A N D A C C E S SC E N T E R F O R V A C C I N E I N N O V A T I O N A N D A C C E S SC E N T E R F O R V A C C I N E I N N O V A T I O N A N D A C C E S S 2

2000-2015: Period of unprecedented success in global malaria control

2016: estimated 216 million cases of malaria, an increase of 5 million cases over 2015

Deaths reached a similar number to the previous year

WHO World Malaria Report 201729 November 2017


Burden of disease

• Endemic in 91 countries

• 3.2 billion people at risk

• 216 million cases

• 445,000 deaths

WHO reports that progress has stalled and many countries

have reported significant increases in malaria cases


Global Technical Strategy for Malaria 2016–2030, June 2015

http://www.who.int/malaria/publications/atoz/9789241564991/en/

WHO Global Technical Strategy for Malaria


Goal 1*: Development of malaria vaccines with protective efficacy of at least 75 percent against clinical malaria suitable for administration to appropriate at-risk groups in malaria-endemic areas.

Goal 2*: Development of malaria vaccines that reduce transmission of the parasite and thereby substantially reduce the incidence of human malaria infection. This will enable elimination in multiple settings. Vaccines to reduce transmission should be suitable for administration in mass campaigns.

*Target: 2030

Malaria Vaccine Roadmap


“How effective does a vaccine have to be before it should made available?.....

“…. for most countries it comes down to a complex calculation based on the cost effectiveness, lives saved, illness avoided and the availability of other effective interventions.”

24 July 2015

Malaria vaccine: How good is good enough?

Commercial challenges

“Not a dual-market opportunity”

“ High-risk, high-cost, low return endeavor”


GoalUpdated WHO policy recommendation on the use of the RTS,S/AS01

malaria vaccine in young children in sub-Saharan Africa

OutcomeTimely availability of pilot implementation evidence on RTS,S/AS01 feasibility, impact,

and safety for submission to the WHO ‘s SAGE/MPAC

Output 1

RTS,S/AS01 subnational introduction through EPI

programs in 3 countries

Output 2

Data to answer key

questions on the

feasibility of RTS,S

Output 3

Data to answer key

questions on the

impact of RTS,S

Output 4

Data to answer key

questions on the

safety of RTS,S

Output 5

Oversight and analysis to

support evaluations

Malaria Vaccine Implementation Programme (MVIP):Goal, Outcome, and Outputs


Regulatory and supply• National regulatory agencies have

authorized vaccine for use in pilots

• Initial shipment of doses from manufacturer anticipated August 2018

Planning vaccine introduction in Ghana, Kenya and Malawi

• Country-led technical working groups or national task force functioning to steer the MVIP activities in-country

• Vaccine introduction plans and budgets finalized by countries

• Country communications and community sensitization plans in place

• MoUs between WHO and MoH under development

MVIP Status (June 2018)

Pilot evaluation status

• WHO and GSK (Phase 4 study) finalizing contracts with evaluation and research partners

• PATH (Health Utilization Study and Health Economics Study) contracted with research partners

Governance

• Programme Advisory Group (PAG) and Data Safety Monitoring Board (DSMB) now functional

• Periodic updates being provided to MPAC and SAGE

Earliest introductions planned for Ghana -September, Malawi - October, Kenya - 2019


RTS,S update

A. Follow-up extension study (2 years) in three Phase 3 clinical trial sites assessing rebound in severe malaria and clinical malaria (MAL072, completed)

B. Assessment of fractional dose and delayed schedule regimen with up to three annual booster doses examining both protection against uncomplicated and severe malaria as well as protection against infection (MAL094/095)

• 1500 young children age (5-17 months old) in Ghana and Kenya• Interim results available 2021

D. Seasonal Malaria Vaccination (RTS,S/AS01) and Seasonal Malaria Chemoprevention (SP/AQ) (RTSS-SMC) – Burkina Faso and Mali; ongoing, results available 2020

C. Dose optimization of fractional RTS,S doses with and without dihydroartemisinin/ piperaquine plus low dose primaquine (Bangkok, Thailand)


Sanaria update

• Sanaria is a small, privately owned, biotech company focused on developing a P. falciparum malaria vaccine to protect travelers and for eventual use in malaria elimination

• 3 types of P. falciparum vaccines are under development by Sanaria. All three vaccines rely on the underlying technology which uses aseptic, purified, live (metabolically active), cryopreserved sporozoites harvested from infected Anopheles mosquitoes, frozen in liquid nitrogen vapor phase, and administered by direct venous inoculation.1. PfSPZ are radiation-attenuated sporozoites from the NF54 strain (African origin) of P.

falciparum parasites. 2. PfSPZ-CVac are live non-attenuated sporozoites from the NF54 strain of P. falciparum

parasites administered by direct venous inoculation to human subjects with the anti-malarials (chloroquine) to prevent blood stage parasitemia.

3. PfSPZ-GA1 are genetically-modified P. falciparum sporozoites which halt development in the early liver stages.


Sanaria’s PfSPZ vaccine

• Over 40 clinical trials listed on the clinicaltrials.gov web site

• Majority are trials that evaluate safety, immunogenicity, and efficacy using the Controlled Human Malaria Infection (CHMI) challenge model using sporozoites as challenge inoculum from the same homologous strain used in the manufacture of the vaccine.

• Three Phase 2b trials have been completed in Sub-Saharan Africao Adults in Mali (2.7 x 105 PfSPZ x 5 immunizations) and Burkina Faso (2.7 x 106Pfz x 3 immunizations

with VE estimated between 28-38% against P. falciparum infection.

o Children in Kenya ages 5-17 months were immunized with varying doses of PfSPZ (KSPZV1) and followed for both clinical malaria and severe malaria. As of June 2018 no results have been presented or published.

• PfSPZ vaccine for malaria elimination on Bioko Island, Equatorial Guinea in planning stages


http://www.euvaccine.eu/portfolio/vaccine-development

Second generation malaria vaccine projects: European Vaccine Initiative Portfolio


Second generation malaria vaccine projects: PATH’s Malaria Vaccine Initiative

http://www.malariavaccine.org/projects/mvi-portfolio


Additional trials:

• Phase 2b Transmission-blocking vaccine Pfs230 EPA/AS01 in Mali. Study ongoing.

http://www.who.int/immunization/research/development/Rainbow_tables/en/

New initiatives in developing monoclonal antibody biologics

• Two ongoing proof-of-concept projects to assess safety and pharmacokinetics following passive transfer of monoclonal antibodies to the circumsporozoite antigen of P. falciparum with CHMI

• One ongoing proof-of-concept project to assess safety and pharmacokinetics following passive transfer of monoclonal antibodies to the Pfs48/45 transmission-blocking antigen of P. falciparum

For additional details of ongoing malaria vaccine projects, please refer to WHO Tables of malaria vaccine projects


Malaria Vaccine Advisory Committee (MALVAC)

Established to provide expert input to help WHO articulate its vision and recommendations on malaria vaccine development

Recommendation for MALVAC to reconvene and assist WHO to:1. Prioritize specific malaria vaccine R&D avenues and value propositions that realistically support

future policy (i.e. 2030)

2. Prioritize targets and preferred clinical development pathways based on evidence review committees and changing public health priorities

3. Propose vaccine use cases in the context of changing epidemiology for both malaria control and elimination scenarios

4. Map out the status of vaccine development, recent progress, challenges, Go/No Go decision framework

5. Develop value proposition and use case for P. vivax vaccine


Malaria Vaccine Advisory Committee (MALVAC), continued

Research and development initiatives:

1. Provide guidance on optimal use of CHMI models and design of early proof-of-concept trials

2. Determine preferred late stage evaluation strategies and advise on safety, efficacy, and implementation & delivery strategies required for WHO policy decisions

3. Discuss research standards in light of status of RTS,S/As01

4. Discuss evaluation strategies (trials, modelling, policy) for vaccine use in elimination

C E N T E R F O R VA C C I N E

I N N O VAT I O N A N D A C C E S S

PATH/Teresa Guillien

Thank you!

[email protected]

malariavaccine.org | path.org

Malaria Update - PDVAC · Malaria Update - PDVAC Christian F. Ockenhouse, MD PhD Medical Director,...

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