KeyeventsinthedevelopmentofPsA-TT,anewmeningococcal

conjugatevaccine

Meningi'sVaccineProjectClosureConferenceAddisAbeba,Ethiopia,February22,2016

FMarcLaForce,MDSerumInsCtuteofIndiaPvt.Ltd.

Threepivotalevents

•  TheMeningi)sVaccineProjectbecomesavirtualvaccinecompanyinMarch2002

•  Anewconjuga)onmethodistransferredfromFDA/NIHtoSerumIns)tuteinDecember2003

•  SerumIns)tutesuccessfullyacceptstechtransfersandscalesupproduc)onfromlaboratorytocommercialscale(04-07)andlicensesanewPsA-TTvaccine,MenAfriVac(2009)

AvailabilityofGroupAMeningococcalVaccinesforSub-SaharanAfricain2001

•  OnlypolysaccharideAvaccineswereavailableandtheywereusedinreac)vecampaigns

•  Over100milliondosesofA/CPSvaccinewerepurchasedbymeningi)sbeltcountriesfrom1999-2003.

•  Thereac)vecampaignswereexpensive,largelyineffec)ve,butpoli)callynecessary.

•  TherewerenoplanstodevelopmeningococcalAconjugate

vaccinesforAfrica.

CreaConoftheMeningiCsVaccineProject

•  Theterriblemeningi)sepidemicin1996leadAfricanpublichealthofficialstoaskWHOtohelpthemaddressthisproblem.

•  Interna)onalmee)ngsorganizedbyWHOin2000and2001recommendthatconjugatemeningococcalvaccinesbedevelopedforAfrica.

•  Aninformalcollabora)onbetweenPATH,WHOandCDC/Atlantafurtherassesstheproblem.

•  InJune2001theMeningi)sVaccineProject(MVP)iscreatedwithGatesFounda)onsupportasa10yearpartnershipbetweenWHOandPATH.

Goal:toeliminateepidemicmeningi'sinAfricaasapublichealthproblemthroughthedevelopment,tes'ng,licensure,andwidespreaduseof

conjugatemeningococcalvaccines

InformingAfricanpartnerswhilebeLerunderstandingtheproblem–Fall2001

•  MVPdiscussionswithAfricanpublichealthofficialsandWHO/AFRO(Harare,Niger,BurkinaFaso,Nigeria)yieldedconsistentinforma)on

–  Costofvaccinewasthemostimportantlimi)ngfactortotheintroduc)onofnewvaccinesinAfrica

–  Meningi)sbeltcountriesareamongthepoorestintheworld

–  SuccessofMVP(widespreaduseofaconjugatemeningococcalvaccineinmasscampaigns)wouldnotbepossibleunlessvaccineswerepricedlessthan$US0.50perdose

Earlypressuresin2001

•  DiscussionswithPharmahadalreadybegunwithWHOin2000andWHO/PATHinearly2001.

•  Generalexpecta)onthatMVPwouldnego)ateacontractwithamul)na)onalforthedevelopmentofanA/Cconjugatevaccine

Product development with established vaccine manufacturers

MVP Provides funds and monitors

Vaccine company Development, production, regulatory, clinical, fill/finish

Finished Product

MVPnegoCaConswithPharma(01-02)

•  Mee)ngswithChiron,BaxterandGSK(September2001–March2002)

•  Keyissuesinthenego)a)onsincluded:– Vaccineprice– Guaranteedpurchase(effectofvolumeonprice)–  Investmentstoincreasemanufacturingcapacity– Crea)nga“norisk”model

MVPbecomesavirtualvaccinecompanyMarch2002

•  MVPcouldnotreachanagreementwithmajorvaccinemanufacturersandnego)a)onsendinMarch02

•  Acerconsulta)onswithMVPTechnicalandManagementCommideesandtheGatesFounda)on,MVPelectstobecomeavirtualvaccinecompanywiththegoalofdevelopingaGroupAconjugatevaccine.

•  Crucialelementsinmakingthisdecisionincluded–  InputsfromAfricanpublichealthofficialsontheimportanceofvaccineprice

–  AvailabilityofabusinessplancommissionedbyTeresaAguadoandLuisJodar

atWHOindica)ngthat“costofgoods”formaking25-50milliondosesofaMenAconjugatevaccinecouldbeaslowas$US0.18perdose.

–  Inputfromfourconsultants,CostanteCeccarini,JeanPetre,ArtElliotandDanGranoffwhoseopinionswerehighlyvalued.

MVP product development plan

MVP Funding, technology

development

Developing country manufacturer Scale up, fill finish

Licensed vaccine

Contract manufacturer PsA and TT

Tech transfer Clinical and regulatory Tech transfer

Challenges and opportunities with new development model

Challenges •  Greater risk •  More complex technical and

managerial issues •  Identifying technology •  Technology transfer •  Clinical trials

•  Changes in Nm epidemiology •  Non A meningitis •  Bivalent product

Opportunities •  Low vaccine cost •  IPR issues straightforward •  Opportunity cost issue

resolved •  Tailor-made vaccine for

Africa •  Strengthens developing

country capacity •  Model for other vaccines

ConjugaConofPSAtocarrierprotein

•  SynCoBioPartners,acontractmanufacturerfromAmsterdam,chosenasaPSAmanufacturer

•  TTselectedasthepreferredcarrierprotein

•  Iden)fyingaconjuga)onmethodtoprepareaPsA-TTconjugatevaccine–  Pharmauninterestedinsharing/sublicensingIP–  InJune2002MVPbeganworkingwithEuropeanbiotechcompanywithextensiveexperiencedevelopingPSconjugatevaccines

“Emerging” vaccine manufacturers expressing interest and visited

•  BioFarma(Indonesia)•  BioManguinhos(Brasil)•  BirMex(Mexico)•  Finlay(Cuba)•  SerumIns)tuteofIndia(India)

TroubleswithconjugaConIP(June2003)

•  Novelconjuga)onmethoddevelopedbyBiotech;testlotsofPsA-TT(laboratoryscale)madeandsuccessfullytestedinmice

•  AtaUKmee)nginMarch2003theMVPTechnicalAdvisoryGroupapprovedtechtransferofmethodtoSerumIns)tuteinJune

•  ThedevelopmentBiotechpartnerwithdrewfromtheprojectinJune2003.

Falloutfromfaileddevelopmentpartnership(Summer2003)

•  Majorblowtotheproject•  Severalvaccineexpertsopined“Wetoldyouso…theseareonlyamateurs…”

•  Opencri)cismoftheprojectatJuly2003WHOSAGEMee)ng

•  Significantmoraleproblemsintheproject•  InternalreviewatMVPinlateJuneconcludedthatthedevelopmentstrategywassoundbutthatapoorpartnerchoicehadbeenmade

Productdevelopmentworkrestarted

•  InJuly2003MVPrequestedproposalsfrom2publiclaboratoriesand4vaccinemanufacturers

•  MVPreceived4proposalsthatwereevaluatedbytheMVPExpertPanelinOctober2003– Nofinalrecommenda)onmadebuttwoavenueswerechosenforfurtherevalua)on

•  Transferaconjuga)onmethodfromCBER(FDA)toSerumIns)tuteofIndia

•  AskBaxter,aUS-basedPharmacompany,tomakebulkMenAconjugateforfill/finishatSerumIns)tute.

FDAandtheNIHstepup•  CarlFraschhadindicatedinMay2003thatarobust

conjuga)onmethodforNmAhadbeendevelopedbyRobertLeeatCBER/FDAandwasavailable

•  DiscussionswithFDAbegininlateJune•  Muchofthebackgroundworkhadalreadybeendoneby

Drs.LeeandFrasch•  Confirmatorytes)ngoftheCBER/FDAvaccinewasdoneby

DanGranoffinOctober2003.Heconcluded“…thisisthemostpotentMenAconjugateJhadevertested.”

•  Transferformali)eswererapidlynego)atedattheNIHOfficeofTechnologyTransfer(PSoukasandCOdoson)

•  TechnologytransfertoaSerumIns)tuteteambeganinBethesda,MDduringthe2003Christmasholiday.

SerumInsCtutesuccessfullyacceptstransferofFDAconjugaContechnology

•  PreclinicallotsofPsA-TTpreparedinMarch2004•  FormalagreementbetweenPATHandSerumIns)tutesignedinJuneof2004

•  GMPproduc)onisgraduallyscaledup•  Analy)ctechniquesdeveloped•  AdedicatedfacilityisbuiltinPunewithcostssharedbetweenMVPandSerumIns)tute

Productdevelopmentdecisions2004-2009

•  PsA-TTfromSerumIns)tuteusingtheFDAconjuga)onmethodweretestedatNIBSC(PodersBar,UK)inNovember2004

•  ResultswerereviewedandapprovedbyMVPExpertPanelandWHOSAGEmembersinNovember04–Godecisionrendered

•  ClinicaltrialsofthePsA-TTvaccinebeginin2005.•  MenAfriVacislicensedbytheDrugsControllerGeneralofIndiainDecember2009

Lessonslearned•  PDPvaccinepartnershipscansolveimportantpublichealth

problemsbutthescien)ficbasemustbesolid•  Expectcri)cismifyouaredoingsomethingnew•  Recognizeandaccommodatetoculturalreali)es•  Chooseconsultantswhoaresmartandcandidbutalsohave

soundinterpersonalskills•  Thebusinessmodelmustbeacceptabletoallpartners•  Facetoface)mewithpartnersisessen)al;whenindoubt–go

visit•  Iden)fyandpayaden)ontothekeyplayers,worktounderstand

whattheywant•  Betransparentandcommunicate,communicate,communicate…

The Meningitis Vaccine Project

The2001MVPvaluesstatement•  Theprojectisaboutpublichealthimpactandnotsimplymakingvaccinesavailable•  Decisionsaboutcandidatevaccineslinkedtointroduc)onstrategiesandlikelyfinancial

constraints•  AfricanpublichealthofficialstobecloselyinvolvedwithMVP