改善医疗保健中的细胞和基因治疗基础设施

SUPERCHARGINGHEALTHCARESYSTEMSFORCELLANDGENETHERAPIES SarabvijaySinghTobiasHandschuh Thiswhitepaperisanoutputofarecentcellandgenetherapy(CGT)roundtableconvenedbyOliverWymantobringtogetherindustryleadersacrossbiopharma,payerandprovider organizationstodiscussthecurrentstateofplayforcellandgenetherapysiteofcaremodel,futureoutlookandkeysuccessfactors. There’salotofoptimismaroundcellandgenetherapiesandthepotentialtoreshapepatientcare.Everybreakthroughgeneratesmoreenthusiasmthatpatientswillgetaccesstoinnovativetreatmentsforlife-threateningdiseases,withCAR-TschanginglongtermoutcomesdramaticallyforconditionssuchasBcelllymphomaandacutelymphoblasticleukaemia(ALL),whilegeneaugmentationtherapiesaredoingthesameinconditionssuchasmusculardystrophy(SMA)andmutation-associatedretinaldystrophy. NewtherapiesforHemophiliaAandBarecomingtomarket,andmanyothersthataddresslargervolumeindicationslikeParkinson’sDiseaseareprojectedtolaunchinthenear-tomid-term.Asizeableportionofdrugsprojectedtolaunchby2028areaimedatdiseasesimpactingonein5,000people,orevenonein1,000,significantlyhigherthanthetreatmentslauncheduntilnow,whichgenerallytargeteddiseasesaffectinglessthanonein50,000oreven100,000.Payersandregulatorshavebeenmakingheadwayinrevampingtheirassessmentframeworkstomakeroomforinnovation,whilehealthsystemsarelaggingindevelopingtherightcapacityandcapabilitythatwillbeneededtoscaleupinthefuture. Severalfactorsimpactwherecellandgenetherapiescanbedelivered,includinghowsafetheyaretouse,thecapabilitiesandinfrastructureneededtoadministertreatments,andhowmuchfinancialburdenisputonprovidersbeyondthecostofthedrug.Althoughnoteverymodalitywithincellandgenetherapyfacesthesamechallengesfromatreatmentdeliveryperspective,productsthathavelaunchedtodatehavebeenlimitedtoasubsetoftertiarycare,mostlyacademicinstitutions.Biopharmacompaniesareindividuallycertifyingandaccreditingsitestomakesuretheyhavetherightcapabilities,infrastructure,andprocessesinplacetohandletheproductandmanagepatients.Sitesgenerallyhavetomeetarangeofrequirementsanduseorderingsystemsdevelopedbyindividualmanufacturers,creatingcomplexityanddrainingresources. Scalingcellandgenetherapyrequiresadvancingbeyondthecurrentmodelandaddressingbottleneckssuchashighlydiverseandcomplextreatmentdeliveryprocess,supplychains,capacityconstraintsandscarcecapabilities.Thisisoftencompoundedbymisalignedfinancialincentivesbetweenmanufacturers,payers,administeringphysiciansandhospitals. Exhibit1:Treatmentdeliveryrequirementsvarybymodalitytype GeneaugmentationtherapyAutologouscelltherapy Viralvectorloadedwiththecorrectivegene;Offtheshelfproductforanamedpatient;systemicorlocaldelivery. E.g.,Zolgensma,Luxturna Geneticallymanipulatedpatientcells;highlycomplexprocesswithshortturnaroundtimesandnomarginforerror.E.g.,Kymriah,Yescarta Safetyconsiderations Varybyindicationandrouteofadministration;examplesinclude •Liverfunction•Plateletcounts •Developmentofviralvectorantibodies(NABs)•Proceduralcomplexitye.g.,ICMinjection Varybyproduct,examplesinclude•Cytokinereleasesyndrome—canleadtoorgandysfunctionanddeath •Neurologicaltoxicity(ICANS) Capabilityrequirements Examplerequirements:•Storage65C,administrationin3-4hoursafterthawingduetolimitedshelflife•TrainedPharmacist(s)foronsiteproductprepunderasepticconditions•Trainedpersonneltoconductsurgery(e.g.,forICMinjection,intraocularsurgery)•Complexpatientapprovalandpayernegotiations•MDTtomanageadverseeventsandposttreatmentmonitoring Examplerequirements:•Multidisciplinarycelltherapyconsultationteamtodetermineeligibility•Infrastructureandstandardsforapheresis,cellcollection,storage,shippingandtrackingofcelltherapyproduct•Stafftrainedinmanagingcomplexlogisticsandpatientapproval –Schedulingandcoordinationwithmanufacturerportaltoensureappropriatetimingbetweenbridgingchemo,leukapheresis,andadministration–Referrals,clinicalevaluation,PAsandsinglecaseagreements •Policiesandproceduresforadverseeventmanagement,REMsadherence,patientfollowupandqualitytracking Reimbursement •PriorAuthorizationalwaysneeded,reimbursementvariesbypayertype,mostpushingforbypassingbuyandbillandusingspecialitypharmacy todeliverintime •AppropriatecodestocoverE2Etreatmentmaynotbeavailableatlaunch•ComplexVBAsinplace(payforperformance)thatrequiredatacollection •Gapbetweencostandreimbursementforprovidersusedtobeapproximately$186,000in2020 •In2022,DRGwasadjustedto $246,000,selecthospitalsmayreceiveadditionaladdonforproductswithNTAPstatus,butlimitedto65%ofproductcosts.EvenwiththeseadjustmentsCAR-Tcasesoftenfailtocovertotalcostsforproviders Complexityforproviders LowHigh Source:OliverWyman LEARNINGFROMTRANSPLANT Theevolutionoftransplantcareoffersaroadmapforscalingcellandgenetherapy.Likecellandgenetherapies,theuseoftransplantscomewithsignificantsafetyconcerns.Thistranslatesintotheneedforahighlyskilledworkforceandcontinuouspatientmonitoring.Advancesinscienceandtechnology(e.g.,greaterunderstandingofHumanLeukocyteAntigens(HLA)matchingandcomplicationssuchasGVHD),standardizationofdeliverycapabilities,andclearalignmentonfinancial