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New therapeutic and preventive New therapeutic and preventive

New therapeutic and preventive - PowerPoint Presentation

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New therapeutic and preventive - PPT Presentation

medicines to fight the Ebola epidemic December 2014 Status report 16 December 2014   Date of situation report Confirmed Probable Suspected Total Deaths Guinea ID: 753099

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Slide1

New therapeutic and preventive medicines to fight the Ebola epidemic: December 2014 Status report

16 December 2014Slide2

 

Date of situation report

Confirmed

ProbableSuspectedTotalDeathsGuinea13-Dec2,115263162,3941,518Liberia9-Dec2,9461,8013,0507,7973,290Sierra Leone13-Dec6,638791,5568,2732,033Total 11,6992,1434,62218,4646,841

Cumulative EVD cases and deathsSlide3
Slide4

Ebola epidemiological curve*Data represents confirmed cases in patient database and situation report

**For Liberia, laboratory

confirmed cases have been available

at the country level since 03 November in the situation reportLatest Sitrep13 Dec - GN09 Dec - LB13 Dec - SLSlide5

Ebola epidemiological curve*Data represents confirmed cases in patient database and situation report

**For Liberia, laboratory

confirmed cases have been available

at the country level since 03 November in the situation reportLatest Sitrep13 Dec - GN09 Dec - LB13 Dec - SLSlide6

Cumulative EVD infections in health-care workers,as of 16 December 2014Country

Case definitionTotal Cases*

Total

DeathsGuineaConfirmed10350Probable99Suspected00Total11259LiberiaConfirmed197115Probable6629Suspected10139Total364183Sierra LeoneConfirmed216105Probable388Suspected5721Total311134All countriesConfirmed516270Probable11346Suspected15860Total787376Source: Patient database as of 15th December 2014*Includes patients for which outcome data is unavailableSlide7
Slide8
Slide9

Development Testing

Licensure

Plan for use

Accelerating access to vaccines and therapeutics is a high priorityIn parallel…Slide10

Accelerating access to Ebola vaccinesFrom research to large scale use

Dr Ana Maria Henao-Restrepo MD MSc

Group Leader, Vaccine Phase 3 trials and early deployment

Experimental Ebola therapeutics and VaccinesSlide11

Is the vaccine safe and effective?Which of the technologies to be used?What is the Target Product Profile and implications?

How can clinical trial programs be accelerated?

What is the benefit-risk profile and can the Vx be used at population level?

What are the post-licensure activities / surveillance / adverse events?What surveillance systems are in place?How can we mitigate supply risks and accelerate supply scale-up?What is the most likely supply map in short and long term?What are different supply scenarios (dosage, yield, scale-up)?What demand scenarios exist (age, geography, stockpile…)? What to do to ensure formulation is as suited to use as possible?What are vaccination strategies to use and why (e.g. ring-vaccination, cohorts, HCPs, high intensity areas, high risk countries)?What are different access scenarios?What is the recommended use for the initial vaccine stocks?Who can finance and how?How to best organize procurement?What is the right framework to think about liability?Mechanism of vaccine administration in different populations?How to manage the cold chain and logistics of distribution?What are the main drivers of cost and how can they be controlled?Key issues to considerA comprehensive scale-up plan Focus todayPlanClinical trials and tech choiceRegulation and safetySupply -demand Vaccination strategies & Access Scale-upEnablersABC

D

E

FSlide12

rVSV-ZEBOV Recombinant vesicular stomatitis virus

It aims to induce EVD-specific immune responses.Merck/NewLink

Pharmaceuticals/Public Health Agency of Canada

ChAd3-ZEBOV Chimpanzee adenovirus 3It uses a chimpanzee adenovirus that does not grow, containing the gene for EVD surface protein.GSK/NIAIDEbola vaccines currently under clinical evaluationKanapathipillai R et al. N Engl J Med 2014. DOI: 10.1056/NEJMp1412166Slide13

13

Ebola recombinant protein

Protein Sciences

(1st trimester 2015 ) DNA expressing Ebola glycoprotein with electrophoration. Inovio (2015) Oral adenovirus 5 Ebola vaccineVaxart(1st quarter 2015) Alternate rVSV Ebola vaccineProfectus(mid- 2015) Recombinant rabies virusThomas Jefferson Univ. (2015) Adenovirus, lentivirus and influenza virus based Ebola candidates. Russian candidates (2015) Ebola recombinant nanoparticle with Matrix M adjuvant Novovax (1st quarter 2015) Ebola vaccines under Preclinical evaluationAd26/Ad35/MVA J&J/Crucell(Jan 2015) Jan 2015Dec 2015June 2015Description, developer(estimated date when clinical testing will start)HPIV-3 live attenuated Intranasal (two versions), NIAID (March/April 2015) Rabies Ebola gp inactivated,Intranasal, NIAID (2015) Slide14

Near-term development plan

GMP grade vaccine

Emergency use

under informed consent Data collectionLarge-scale vaccinationNon-affected areasAffected areasSept-Nov2014Non-clinical eval inNHPsPhase 1Safety and dose selection1st Quarter 2015Phase 2aLarge scale safetyPhase 2bPreliminary efficacy Phase 3 EfficacySlide15

15

Ebola vaccines in clinical testing- Phase 1 studies

VRC-USA

Bivalent 20 healthy adultsDose-escalation, SafetySept 2014Oct 2014Oxford-UK Monovalent60 healthy adultsDose-escalation, SafetyLausanne-SuisseMonovalent100 healthy adultsDose-escalation, SafetyWRAIR-USA30 healthy adultsDose-escalation, SafetyNIAID-USA30 healthy adultsTwo dose schedule, SafetyHamburg-Germany30 healthy adultsDose-selection, SafetyNov 2014Lambarene-Gabon60 healthy adultsDose-selection, SafetyKilifi-Kenya40 healthy adultsDose-selection, SafetyGeneva-Suisse100 healthy adultsDose-selection, SafetyCVD - MaliMonovalent80 healthy adultsDose-escalation, SafetyrVSV: Phase 1 trialsChAd3: Phase 1 trialsSlide16

16

Ebola vaccines in clinical testing -

Plans for phase 2, 3 studies

Jan- Feb 20152nd Q 2015Phase 2 multisite multi-country RCT Single common protocol -total of ?3000 including ?500 children, - other special populations?Possible countries are Ghana, Mali, Cameroon, Nigeria, Senegal, Cote d’IvoireSafety, ImmunogenicityLiberia-MonroviaNIH- ChAd3 + rVSVRCTs3 arm study Efficacy, SafetySierra LeoneCDC(rVSV-ChAd3) Stepped WedgedEfficacy, SafetyGuineaConsortium (rVSV and?or ChAd3)Ring Vaccination and FLWsEfficacy, SafetyEarly results of vaccine efficacySlide17

17

Initiation of Phase 1 trials for the two most advanced vaccines

Ebola Vaccines - Key milestones

Sept - Oct 20152nd Q 2015Nov-Dec 2015Agreed protocols (including Phase 3) trials across sitesPreparation started of sites for Phase 3 studies in Ebola affected countriesInitial safety and immunogenicity from Phase 1 trials availableStart of Phase 3 trials in Ebola affected countries1st quarter 2015Early results of vaccine efficacySlide18

There is consensus that the use of whole blood and convalescent blood serums needs to be considered as a matter of priority.

Use of convalescent whole blood or plasma collected from patients who have recovered from Ebola virus disease for transfusion as an empirical treatment during outbreaks

Whole blood and convalescent plasma

WHO guideline (Sept 2014):Identification of patients recovered from EVD as potential blood donorsInformed consent and selection of donorsDonor’s blood grouping and screening for transfusion-transmissible infectionsBlood collection and donor careLabelling, storage, and transportation of blood and plasma products to sites where transfusion is givenSelection of EVD patients for this interventionClinical transfusion processData collection at the transfusion siteAssessment of effectiveness of this empirical treatmenthttp://apps.who.int/iris/bitstream/10665/135591/1/WHO_HIS_SDS_2014.8_eng.pdfSlide19

Other Adjacent countries – strengthening preparedness:

mtg end Feb

Expatriated patients – receiving convalescent plasma

Blood ProductsGuineaGuinea/Belgium/UK/France Guinea/Belgium/UK/France Deploying imminentlyDeploying imminentlyWhole BloodPlasmaLiberiaGovernmentUS (Clin RM/BMFG)RunningRunningWhole bloodPlasmaSierra LeoneGovernmentOthersRunningPlanningWhole BloodPlasmaNigeriaClin RMTo be deployedTBC (IgG?)Slide20

Effective community engagementDraft WHO document on key considerations for effective community engagement in blood donation for compassionate use and clinical trialsDocument outlines a draft model and key considerations to enable national health authorities, blood transfusion services and trial investigators to effectively engage with communities to prepare EVD survivors and the communities for blood donation and the clinical trialsAims to help to ensure informed participation of

survivors and communities and avoid the additional pressure and anxiety inappropriate and/or insufficient community engagement can place to already vulnerable groups. WHO Ebola Blood and Plasma Working GroupSlide21

Strengthening NBTSIn-depth assessment of BTS conducted in affected countries The NBTS in affected countries have suffered from a decade of under resourcing; in staff recruitment, staff development, facility maintenance, effective consumables procurement, equipment provision and maintenanceThe services were unable to meet the nations’ needs prior to the outbreak - for this emergency the services are

not in a position to support either the compassionate use or the clinical trials Substantial investment is needed to refresh and resource the services during the recovery phaseCountry specific plans for system strengthening

are developed - training

needs are identified – meeting planned for mid-Jan 2015WHO Ebola Blood and Plasma Working GroupSlide22

2- Interferes with viral productionTKM 100802Ebola Target two essential viral genes to stop the Ebola from replicating.

AVI 7537 Sarepta

Molecules that bind viral RNA, blocking gene function.

Favipiravir T705 Disrupts enzymes that the virus uses to make copies of himself.BCX4430 Biocryst Disrupts enzymes that the virus uses to make copies of himself.Brincidofovir Disrupts enzymes that the virus uses to make copies of himself.4- Bolsters human cellsInterferons - Induce an antiviral state in exposed cells and regulates the immune system6- Whole blood transfusions and convalescent plasmaExperimental therapies used to treat Ebola Prioritized for consideration based on the availability of NHP efficacy data with a filovirus challenge and justification for a human dose based on clinical data of the product or comparable products within that class.Source: Adapted from the Washington Post, Oct 7, 20145- Testing existing drugs approved for other purposesAll drugs Screening all licensed drugs.3- Prevents virus from exiting host cells1- Targets the virus before it enters the cellZmapp A cocktail of three monoclonal antibodies, which block or neutralises the virus by binding to or coating a different site on the covering or “envelope” of the virusHyperimune globulin Antibodies that can neutralize the different EVD strains.Slide23

Zmapp (Mapp) siRNA/ AVI-7537 (Serepta

)siRNA/ TKM-100802 (Tekmira)

rNAPc2

(ARCA biopharma) BCX4430 (Biocryst)Favipirivir/T705 (Fuji/Toyama) Brincidofovir (Chimerix)Toremifene InteferonsLamivudine (GSK)AmiodaroneNew Potential InterventionsTherapeuticsSlide24

The ‘stuff’ that is being proposed to WHO for testing in the field…Vulture Gastric FluidChamomile tea

Ayurvedic oilsSilver suspensions

Bath salts

HIV therapiesHomeopathyCrystalsVitaminsMicronutrientsRoot extractsMagnetsElectromagnetic wavesSlide25

Expert trainingFunding for developmentEquipment deploymentIntegrating development into trialsUnderstanding the needsHealth System Building/Repair/DevelopmentSlide26

17 tests under investigation (1 approved for procurement)Others being received4 main purposesIdentification/ ConfirmationField testEntry/Exit testsDetailed test for data gatheringNeed for standards/ standard testingDiagnosticsSlide27

Ensure there are emergency use regulatory pathways in place;Ensure there is rapid and proactive cooperation and collaboration between regulators, and also with WHO, to help accelerate development and evaluation of investigational treatments and vaccines;Drive innovative clinical trial design

for situations like the current EVD emergency where traditional clinical trial designs may not be feasible.Regulators: ICDRA recommendations to Member StatesSlide28

Rapidly provide scientific information on the potential therapies and vaccines for EVD, and ensure the information is regularly updated;Establish and lead a network of regulators globally to address the response to EVDFacilitate collaborations between regulators in countries where products are being developed and those in

countries where the products will be evaluated and, if found safe, usedRegulators: ICDRA recommendations to WHOSlide29

Research fields include; Therapeutics, Diagnostics, Vaccines, Epidemiology, Virology and Behavioural dynamicsTrans-disciplinary approachBetter future responseInvestigating what we could understand about disease immunopathogenesis, viral progression and viral sheddingThis could benefit patient care, infection prevention and control and contact managementWhat can we learn about the behavioural dynamicsThis could benefit every level of our intervention in country, with all actions being impactedResearchSlide30

RumoursInterventions without evidential basisCommunity engagement (large and small scale)AwarenessSafetyIn the field“Any man's death diminishes me,

Because I am involved in mankind”John DonneSlide31

Back-up slidesSlide32

328. Considerations on operational (non-vaccine) financial needs Slide33

33

Considerations on operational (non-vaccine) financial needs for roll out of vaccination strategiesType of

vaccination

strategy SpecialconsiderationsEbola vaccineTypicalcampaign costsPlanning, management and coordinationSlide34

Possible Ebola Vaccination Strategies

34

Mobile teams

Ring vaccinationSimilar to measles campaignsHealth care centreHCWs in ETCsCommunity basedEbola respondersContacts of Ebola patientsHome-based care takers of Ebola patientsTarget age groups:Children < 15 yoTarget age groups:Adults older than 15 yoPregnant womenPeople living with HIVSlide35

Ebola vaccination campaignsPlanning, management, and coordination

35

Before campaign

During campaignAfter campaignHigh quality microplanning/preparation to identify target population, and to identify logistical and funding requirements Campaign “readiness dashboards” might be consideredAvailability of data for decision making on an hour by hour basis to identify and manage issues and bring reinforcementsReal time tracking and reporting of vaccination team supervision.Vaccine coverage monitoringCoordination of data managers at district, regional, national levelsAssessment of vaccine coverageEvaluation of lessons learned Drafting guidelines for Ebola vaccination campaign managementSlide36

36

0.2

2.0

PolioMeaslesHPV0.63.03.05.0Estimated cost per person vaccinated (USD)Medical volunteers travel house to house to identify and vaccinate children aged <5 years with oral polio vaccine Trained health workers work at permanent, temporary or field posts to vaccinate children aged <5 years with injectable measles vaccineTrained health workers travel to schools to vaccinate adolescent girls with injectable HPV vaccineTypical operational costs of other types of vaccination campaigns543210Slide37

Operational costs of an Ebola vaccine campaign are likely to be higher than those of other campaignsCategory

Social mobilisation to explain target populationsTraining and supervision for a new “special” vaccine

More human resource requirements may be needed

Transport to access remote locations Immunisation session supplies for vaccine monitoring OtherSlide38

Special considerations for an Ebola vaccine campaign plan are pertinentCategory

Cold chain equipment/special logisticsSecurity and crowd control

Infection control programme and supplies

Monitoring of Adverse Events Waste management Slide39

Stockpiling challenges are more than financing and vaccine supply future outbreaks might involve other strainsphysical/behavioural interventions may continue to be the mainstay of outbreak control

timing of outbreaks is somewhat unpredictableneed international mechanism to manage stockpile

39Slide40

40

African Vaccine Regulators Forum (AVAREF): Review of IND application: Protocols, IB, Ethics and informant consent

WHO Advisory Committee on Regulatory Emergency Authorization of unlicensed Ebola Vaccines

: Review of GMP, evidence on safety and efficacy, programmatic suitability. Time limited authorization for use.National Regulatory AuthoritiesWHO Ebola Vaccines Risk Assessment Group and WHO Global Advisory Committee on Vaccine Safety: Evaluation of safety data and opinion on potential risks and benefits{4C3C2611-4C71-4FC5-86AE-919BDF0F9419}Slide41

"The vaccine is not the magic bullet. But when ready, they may be a good part of the effort to turn the tide of this epidemic.”41Slide42

Acknowledgements42