全球视野下：ADC的trial策略.pdf

ADC Clinical Trial StrategyShuhua Zhou（周淑华）PhD CitelineMar.9th20241.ADC领域的市场空间和临床试验启动趋势2.临床可行性评估（患者数量，临床时长，Patient journey）3.ADC临床开发的适应症和患者、主要终点选择4.ADC临床试验的Combo趋势OutlineOutlineADC Drugs with High Likelihood of ApprovalADC Drugs with High Likelihood of ApprovalSource:Biomedtracker and PharmapremiaADC Drugs WW sales forecastADC Drugs WW sales forecastBreast cancerBladder cancerNon-small cell lung cancer(NSCLC)Non-Hodgkin lymphoma(NHL)Hodgkin lymphomaOvarian cancer-0.20%0.00%0.20%0.40%0.60%0.80%1.00%-2000-1000010002000300040005000600070008000Indication Market ShareSales Change Over TimeIndication Market Share Change/2028(m$)Source:Evaluate Pharma Accessed 2024 7,469.810,118.313,585.117,501.421,934.326,516.631,227.50.05,000.010,000.015,000.020,000.025,000.030,000.035,000.02022202320242025202620272028Indication sales(m$)WW Sales by Indication($m)CAGR 26.9%ADC Drugs Trials by Start DateADC Drugs Trials by Start Date0501001502002502023202220212020201920182017201620152014201320122011201020092008200720062005200420032002200120001999199819971995Trial NumberIVIII/IVIIIII/IIIIII/IIISource:Trialtrove1.ADC领域的市场空间和临床试验启动趋势2.临床可行性评估（Patient journey，患者数量，临床时长与成本）3.ADC临床开发的适应症和患者、主要终点选择4.ADC临床试验的Combo趋势OutlinePatient Demographics and Patient JourneyPatient Demographics and Patient Journey Better understanding of patient dynamics to assist with pharma company strategic planning improve clinical trial design for pipeline drugs and patient targeting for launched drugsReimbursement claims data analysis enables the investigation of patient demographics for more accurate estimation of the patient population with a particular disease,as well as patient distribution by state or other geographic regionSuch analysis is vital when planning clinical trials and assessing the potential future value of a product,particularly when other sources of epidemiology data are unavailable or unreliable,as is often the case with rare diseasesReimbursement claims data analysis can also be used to inform pharma companies about the patient journey,e.g.,whether patients mostly seek care at hospitals or clinics,referral patterns,treating physician specialties,etc.DescriptionDescriptionExamplesExamplesTurn RTurn Real World Data(RWD)into Insights eal World Data(RWD)into Insights Multiple data sets enter Multiple data sets enter our platformour platformData is cleansed and Data is cleansed and harmonizedharmonizedNorstellaNorstella data assets are data assets are appendedappendedCombined data powers Combined data powers products and servicesproducts and services300M+300M+Longitudinal patientsLongitudinal patients2.1M+2.1M+HCPsHCPsMatching&normalization Matching&normalization integration processintegration process32B+32B+Claims200M+200M+Annual Patients300M+300M+Overall Patients(2017 Present)LabsLabsRx+Rx+EMREMRAdditional DatasetsAdditional DatasetsEpidemiology dataEpidemiology dataFormulatory&enrollment dataFormulatory&enrollment dataHEOR dataHEOR dataSites&investigators dataSites&investigators dataClinical trials dataClinical trials dataPublications dataPublications dataBetter Insights Faster Related to:Better Insights Faster Related to:Clinical Trial PlanningClinical Trial PlanningProtocol OptimizationProtocol OptimizationSite&PI SelectionSite&PI SelectionCommercial StrategyCommercial Strategy 300M+total patients from 2017 forward 200M+patients annuallyGranularityGranularityCoverage by Payer TypeCoverage by Payer Type 80%of commercial lives 60%of Medicare lives 40%of Medicaid lives Patient Geography at Zip level Site-of-care address Demographics(age,race,gender)Out-of-pocket costs Weekly data refreshesPatient VolumesPatient Volumes+300M Patients+300M Patients+7K Hospitals+5,600 Health Systems+1,500 ACOs+6.5M AffiliationsGranularityGranularity NPI,First/Last Name IDN Affiliations Affiliation Hierarchy Differentiation of treatment settings-(inpatient/outpatient)Line-item charge details Behaviors&decisions of physicians,assistants,nurse practitioners,registered nurses,and other healthcare staffGranularityGranularity+2.1M HCPs+2.1M HCPs Specifics by benefit plan Submissions with Prior Authorization(PA),Quantity Limit(QL),and Step Therapy(ST)specificity Remittances with allowed amounts Denials with rationale specificity Denial reasons Rebates,coupons,deductibles,co-insurance and full payment amountsPayer Detail AvailablePayer Detail Available98%of Payers98%of PayersBenchmark to ADC Phase I&Phase III Trials in Last 10 YearsBenchmark to ADC Phase I&Phase III Trials in Last 10 Years012345678910Number of TrialsEnrollment Duration(months)Enrollment Duration(Actuals only)Mean:26.68 Median:23.82 Min:11.83 Max:67.16024681012Number of TrialsAccrualAccrual(Actuals only)Mean:546.47 Median:498 Min:106 Max:1,500051015202530354045Number of TrialsReported SitesReported SitesMean:152.38 Median:111 Min:1 Max:1,1450510152025Number of TrialsEnrollment Duration(months)Enrollment Duration(Actuals only)01020304050Number of TrialsAccrualAccrual(Actuals only)01020304050607080Number of TrialsReported SitesReported SitesTrialtrove,Mar 2024Mean:27.4 Median:26.45 Min:1.84 Max:72.65Mean:58.05 Median:36.5 Min:3 Max:292Mean:12.3 Median:7 Min:1 Max:96Phase IPhase IIIADC Trial Enrollment Efficiency in Top 10 Country Last 10 ADC Trial Enrollment Efficiency in Top 10 Country Last 10 Y YearsearsCountryNumber of TrialsAverage Actual Pts/Site/MoChina710.14United States690.13Italy600.13Spain590.14Germany580.13Canada560.15United Kingdom550.13France540.13South Korea530.16Australia490.13CountryNumber of TrialsAverage Actual Pts/Site/MoUnited States1460.68China1030.61Spain460.19Japan391.28France351.62Australia340.15South Korea290.17Canada270.20Italy190.31United Kingdom180.32Phase IPhase IIITrialtrove,Mar 2024Trial Cost Mean BenchmarkTrial Cost Mean BenchmarkIndicationTotal PIII Trial Cost Mean Benchmark($m)Total PII Trial Cost Mean Benchmark($m)Total PI Trial Cost Mean Benchmark($m)Non-small cell lung cancer(NSCLC)2563929Breast cancer3096420Prostate cancer3372521Colorectal cancer1153121Bladder cancer1463423Melanoma1883422Ovarian cancer2493719Hepatoma,liver cancer1952210Head&neck cancers1732320Small cell lung cancer(SCLC)1962117Source:Evaluate pharma1.ADC领域的市场空间和临床试验启动趋势2.临床可行性评估（患者数量，临床时长，Patient journey）3.ADC临床开发的适应症和患者、主要终点选择4.ADC临床试验的Combo趋势OutlinePatient Segment for ADC TrialsPatient Segment for ADC TrialsPatient SegmentNumber of trialsBreast:Stage IV338Breast:Stage III313Unspecified Solid Tumor:Stage IV239Unspecified Solid Tumor:Stage III233Lung,Non-Small Cell:Stage IV229Lung,Non-Small Cell:Stage III207Gastric:Stage IV167Gastric:Stage III162Ovarian:Stage IV149Esophageal:Stage IV140Ovarian:Stage III140Esophageal:Stage III139Bladder:Stage III120Bladder:Stage IV120Colorectal:Stage IV110Pancreas:Stage IV107Pancreas:Stage III103Colorectal:Stage III102Renal:Stage IV92Patient SegmentNumber of trialsBreast:Second line275Lung,Non-Small Cell:Second line202Unspecified Solid Tumor:Second line198Ovarian:Second line152Lymphoma,Non-Hodgkins:Second line146Gastric:Second line144Breast:Third line129Esophageal:Second line122Bladder:Second line104Breast:Fourth line or greater99Colorectal:Second line97Pancreas:Second line91Lymphoma,Non-Hodgkins:Third line85Lung,Non-Small Cell:Third line84Renal:Second line82Endometrial:Second line80Head/Neck:Second line80Lung,Non-Small Cell:Fourth line or greater74Breast:First line71Ovarian:Third line71Trialtrove,Mar 2024Patient Segment for ADC TrialsPatient Segment for ADC TrialsPatient SegmentNumber of trialsLung,Non-Small Cell:PD-L1 Refractory54Lung,Non-Small Cell:PD-1 Refractory50Prostate:Hormone refractory38Breast:PD-L1 Refractory33Bladder:PD-L1 Refractory31Breast:PD-1 Refractory31Bladder:PD-1 Refractory29Head/Neck:PD-L1 Refractory26Renal:PD-L1 Refractory26Head/Neck:PD-1 Refractory25Ovarian:PD-L1 Refractory25Ovarian:PD-1 Refractory24Renal:PD-1 Refractory24Unspecified Solid Tumor:PD-L1 Refractory24Esophageal:PD-1 Refractory23Esophageal:PD-L1 Refractory23Unspecified Solid Tumor:PD-1 Refractory23Gastric:PD-1 Refractory22Gastric:PD-L1 Refractory22Patient SegmentNumber of trialsBreast:HER2 positive207Breast:HER2 negative142Breast:Triple receptor negative114Breast:Estrogen receptor positive90Gastric:HER2 positive81Breast:Progesterone receptor positive78Unspecified Solid Tumor:HER2 positive64Esophageal:HER2 positive59Lung,Non-Small Cell:HER2 negative57Lung,Non-Small Cell:HER2 positive53Unspecified Solid Tumor:HER2 negative45Bladder:HER2 positive44Ovarian:HER2 negative43Gastric:HER2 negative40Esophageal:HER2 negative37Colorectal:HER2 positive35Pancreas:HER2 negative30Bladder:HER2 negative27Breast:PD-L1 Positive27Trialtrove,Mar 2024Primary Endpoints in Registration and Expanded Indication Trials Primary Endpoints in Registration and Expanded Indication Trials with Positive Outcomewith Positive Outcome32302422211712775432222111105101520253035Overall response rateResponse evaluation criteria in solid tumorsComplete responsePartial responseProgression-free survivalDisease ProgressionSafety and TolerabilityOverall survivalProgressive disease rateResponse rateAdverse EventsOverall response rate-durationDose-limiting toxicitiesDuration of overall responseSerious Adverse EventsTime to progressionAccumulation indexArea under the curve scoreCardiac TelemetryClinical benefit rateNumber of trialsPrimary EndpointADC Trials by Primary EndpointsTrialtrove,Mar 20241.ADC领域的市场空间和临床试验启动趋势2.临床可行性评估（患者数量，临床时长，Patient journey）3.ADC临床开发的适应症和患者、主要终点选择4.ADC临床试验的Combo趋势OutlineADC Combination Trials in Phase II and Phase IIIADC Combination Trials in Phase II and Phase IIIIndustry Phase II+Phase III trialsPhase II+Phase III Combination trialsRatioADC89649655%Oncology282091593957%All TA 883963062335%56351410108877666655555550102030405060Immuno-oncology therapyImmune checkpoint inhibitorPD-1 antagonistAngiogenesis inhibitorDNA synthesis inhibitorApoptosis stimulantCD3 agonistCell cycle inhibitorPD-L1 antagonistC-kit inhibitorDNA repair enzyme inhibitorPoly ADP ribose polymerase 1 inhibitorVEGFR-2 tyrosine kinase inhibitorDNA inhibitorDNA topoisomerase II inhibitorEGFR kinase inhibitorErbB-2 antagonistPoly ADP ribose polymerase 2 inhibitorProtein degraderVEGFR-1 tyrosine kinase inhibitorNumber of drugsMechanism Of ActionADC combo drugs by MoATrialrove,Pharmaprojects,20241091915020406080100120LaunchedPhase II Clinical TrialPhase III Clinical TrialNumber of drugsGlobal StatusADC Combo drugsNumber of drugADC drugs92Combo drugs161F Forecasting with Evolving Assumptions at Various Drug Life Cycleorecasting with Evolving Assumptions at Various Drug Life CycleDiscoveryPreclinicalPhase 1Phase 2Phase 3LaunchPost launchIndustry BenchmarksEpidemiologyReal-world DataClinical EvidenceCompetitionPricingTimelinesMarket Access,ReimbursementConstantly evolving inputs with drug lifecycleEstablish Unmet NeedEnsure differentiated value propositionMaximize Launch ROIMaintain Competitive PositionEmpower Your Team with Database Subscription19Assess risk and cost metrics alongside NPV and ROI projections to better predict the market valuation of programmes in a portfolio or landscape.Use consensus forecast data to assess the financial potential of an asset,indication or target.Get a viewpoint on potential ROI should the asset be approved.Global R&D landscape data from preclinical to launch,including data on drugs,companies,development/regulatory statuses,targets,MOAs,and more.Site and investigator data,including contact information,trial experience,US patient proximity and counts derived from medical claims,and a proprietary algorithm that tiers investigators.Clinical trials intelligence,including trial designs,endpoints,trial timing data and visualizations that can be used for planning and benchmarking.ForecastRisk&ReturnValuingDrugsPI&SiteTrialsCompetitor landscape and StrategicReal-time analysis of major market-moving events in the pharma and biotech 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