医药生物：创新药深度研究系列四：从药物经济学看创新药定价逻辑的重塑_37页_2mb (1).pdf

敬请参阅最后一页特别声明-1-证券研究报告 2020 5 22 医药生物 从药物经济学看创新药定价逻辑的重塑 创新药深 度研 究系列四 行业深 度 1 2 3 2019 DRGs 1 First/Best-in-Class 2 First-Follow Me-too 3 First/Best-in-Class First-Follow 增持（维 持）分析师(S0930517110003)021-52523871 联系人-16%-6%3%13%22%04-19 07-19 10-19 01-20医药生物 沪深300 Wind 相关研 报 2019-12-21 ADC 2019-11-21 2019-04-10 2020-05-22 敬请参阅最后一页特别声明-2-证券研究报告 2019 150 119 31 97 70 27 60.7%26.4%3 85%()()()()a)First/Best-in-Class b)First-Follow Me-too c)First/Best-in-Class First-Follow bUyXyWvMyRyRnNoMmQnQpPrM7NaOaQmOpPtRrRlOmMsPfQmOtPbRpOsOuOmQsMvPmOxO2020-05-22 敬请参阅最后一页特别声明-3-证券研究报告 1.4 1.1.4 1.2.4 2.5 2.1.5 2.2.11 2.3.18 3.20 3.1.20 3.2.22 3.3.23 3.4 19.27 3.5 A.28 4.31 4.1.31 4.2.33 5.35 6.36 2020-05-22 敬请参阅最后一页特别声明-4-证券研究报告 1 1.1 2011 FDA 1 024681012141618020004000600080001000012000140002007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 FDA 1.2 1996 1987 1991 1991 Best-in-Class 2-40-35-30-25-20-15-10-50510(1996)(1987)(1996)(1991)(1996)(1991)1 2 3Total-C LDL-C Apo B TG HDL-C Non-HDL-C/HDL-C DrugsFDA FDA Total-C=LDL-C=Apo-B=B TG=HDL-C=2020-05-22 敬请参阅最后一页特别声明-5-证券研究报告 2014 PD-1 Opdivo Keytruda PD-1 Keytruda PD-1/L1 PD-1/L1 2012 3 PD-1%4%0%50%100%150%200%250%300%350%0100020003000400050006000700080009000Opdivo KeytrudaO YOY K YOY-20%-10%0%10%20%30%40%50%60%0 100 200 300 400 500 600 700 800 900 YOY YOY YOY BMS MSD PDB 2 2.1 2.1.1 2016 GDP 17%23 2019 33%Medicare Medicaid 21%16%2020-05-22 敬请参阅最后一页特别声明-6-证券研究报告 5 2017 0 2000 4000 6000 8000 10000 12000 0 20000 40000 60000 80000 100000 120000 GDP Peterson-KFF Health System Tracker 6 GDP 2016 7 2019 0%2%4%6%8%10%12%14%16%18%20%33%21%16%15%10%4%MedicareMedicaid Peterson-KFF Health System Tracker CMS Financial Report for Fiscal Year 2019 2018 1)47%57%2)33%49%2020-05-22 敬请参阅最后一页特别声明-7-证券研究报告 8 2018 47%9 2018 57%美国47%新兴市场24%欧洲发达地区17%发达世界其他地区12%美国57%欧洲17%日本10%其他国家16%Wind Wind 10 2018 33%11 2018 49%欧洲36%美国33%亚洲、非洲、澳大拉西亚21%拉丁美洲和加拿大8%其他地区2%美国49%欧洲19%非洲、亚洲、中东和大洋洲11%中国大陆10%日本及韩国5%拉丁美洲4%其他北美地区2%Wind Wind 2.1.2 2000 1000 500 2020-05-22 敬请参阅最后一页特别声明-8-证券研究报告 12 0 500 1000 1500 2000 2500 美国 意大利 西班牙 土耳其 加拿大 日本阿柏西普 雷珠单抗 Dan Gong Comparison of United States and International Ophthalmic Drug Pricing 2.1.3 Medicare Medicaid PBM1 PBM rebate PBM PBM 1 Pharmacy Benefit Manager 的 简称，即药品福利管理。指介于自我保险的大雇主（为其雇员、退休人员和会员提供处方药赔付）、政府机构、保险公司以及医疗服务提供方 等之间的第三方专业化服务机构。2020-05-22 敬请参阅最后一页特别声明-9-证券研究报告 PBM 13 American Patients First Net Price List Price Neeraj Sood 100 76 35 14 0102030405060708090100 Neeraj Sood The flow of money through the pharmaceutical distribution system 2020-05-22 敬请参阅最后一页特别声明-10-证券研究报告 15 0102030405060708090100 Neeraj Sood The flow of money through the pharmaceutical distribution system 2.1.4 rebate-PBM-Center for Medicine in the Public Interest,CMPI Robert Goldberg 2017 PBM 1300 3490 30%PBM Pricing Action Transparency Report 2016 2010-2016 10%5%2016 40.9%PBM 16 2010-2016 0%5%10%15%20%25%30%35%40%45%2010 2011 2012 2013 2014 2015 2016 Merck Pricing Action Transparency Report 2016 2020-05-22 敬请参阅最后一页特别声明-11-证券研究报告 2.2 2.2.1 90%81%12 17 80%Daiichi Sankyo Group Value Report 2019 2018 27%53%2015 2018 2018 16%2018 10%5%18 2018 27%19 2018 53%40%27%19%5%4%3%2%53%17%12%EMEA9%9%2020-05-22 敬请参阅最后一页特别声明-12-证券研究报告 20 2018%,37.5,60%,10.0,16%EMEA,8.0,13%,4.0,6%,3.1,5%21 2018 10%22 2018 5%57%17%10%16%49%19%11%10%5%4%2%2.2.2 1961 Universal Health Coverage,UHC 3,000 1)3 a)Health Insurance Societies 1300 2016 8 2917 2017 4 1 1357 b)Mutual Aid Associations,MAAs 2014 3 85 MAA 891 2020-05-22 敬请参阅最后一页特别声明-13-证券研究报告 c)Japan Health Insurance Association,JHIA JHIA 2016 8 JHIA 3718 JHIA 2)National Health Insurance,NHI 75 50%3)2008 75 10%23 2017%24 2017%,147805,34%,100970,24%,93301,22%,52750,12%,32040,7%,3131,1%,713,0%,121906,28%,108972,25%,90744,21%,56209,13%,49948,12%,2933,1%1030%7090%7090%Claims Review and Reimbursement Organizations,CRRO Health Insurance Claims Review&Reimbursement Services,HICRRS CRRO 2020-05-22 敬请参阅最后一页特别声明-14-证券研究报告 25 Japan Health Policy NOW 2.2.3 NHI 12 Chuikyo NHI 60 90 26 Drug Pricing System in Japan NHI=National Health Insurance DPO=Drug Price Organization Chuikyo=the Central Social Insurance Medical Council 2020-05-22 敬请参阅最后一页特别声明-15-证券研究报告 1)a)(I)b)(II)2)27 Drug Pricing System in Japan A.(I)(I)SAKIGAKE 1(I)70-120%NHI A B C(I)35-60%(II)5-30%A B C D(I)10-20%A PAL*B I(II)5%A 2020-05-22 敬请参阅最后一页特别声明-16-证券研究报告 B I II 5-20%A B II SAKIGAKE 10-20%SAKIGAKE Drug Pricing System in Japan SAKIGAKE/6/B.(II)(II)NHI 3 6 10 10 15 C.2 a NA b 3818 2012-2014 c NA d=a+b+c e(d+e+f)45.2%/2012-2014 f=(d+e+f)14.7%100%200%50%50%g=(d+e+f+g)7.3%2012-2014 h 8%i=d+e+f+g+h Update of Drug Pricing System in Japan 2020-05-22 敬请参阅最后一页特别声明-17-证券研究报告 D.1)2)a)1.25 1/3/+5/6 b)0.75 1/3/+1/2 2 II 10 3 E.2020-05-22 敬请参阅最后一页特别声明-18-证券研究报告 28 Update of Drug Pricing System in Japan 2.3 Bundestag 2010 AMNOG Arzneimittelmarktneuordnungsgesetz 22 1 Benefit Dossier Gemeinsamer Bundesausschuss G-BA G-BA G-BA Institut fur Qualit at und Wirtschaftlichkeit im Gesundheitswesen,IQWiG IQWiG 2 IQWiG G-BA 3 G-BA 2020-05-22 敬请参阅最后一页特别声明-19-证券研究报告 G-BA Spitzenverband der gesetzlichen Krankenkassen,GKV-SV GKV-SV 6 12 12 SGBV 130b AMNOG 29 AMNOG Friedhelm Leverkus Implementation of AMNOG:An industry perspective SPPE=Sales Price of the Pharmaceutical Entrepreneur 3 AMNOG Major Considerable Minor Not quantifiable None Smaller benefit Friedhelm Leverkus Implementation of AMNOG:An industry perspective 2020-05-22 敬请参阅最后一页特别声明-20-证券研究报告 3 3.1 2017 2019 40 150 5 1)2)10 3)4)5)AMD/DME/CNV 25%T 11%DAA 3.4 85%SGLT2 5 73%85%4 2019 2019 5550 10mg/ml 0.2ml/4160 0.2ml/25%2120 18mg/10ml/1399 18mg/10ml/34%575 10 g/325 10 g/43%31.62 250mg/16.2 250mg/49%39.33 25mg/17.98 25mg/55%3160 40mg/0.8ml 1290 40mg/0.4ml 40mg/0.4ml 40mg/0.8ml 59%2020-05-22 敬请参阅最后一页特别声明-21-证券研究报告 40mg/0.8ml 1644.87 2mg/669 2mg/59%7838 10ml:100mg/2843 10ml:100mg/64%640(62.5 g,25 g)*30 219(62.5 g,25 g)*30 66%293 1mg/1045 5mg/94.5 1mg/378 5mg/68%270 2.5ml:37.5ug 74.8 2.5ml 37.5 g/72%16.29(10mg/)2.56 5mg/4.36(10mg/)73%15120(0.7mg)4000 0.7mg/74%426 10ml/580(15ml/)723 20ml/106.89 10ml/145.8(15ml/)181.72 20ml/75%164.89(100ml/)340(250ml/)40(100ml/)81.16(250ml/)76%89 700mg/19 700mg/79%354.06(200ml:20g/)54(200ml:20g/)85%AMD 2017 DME CNV 2019 5 2019 2017 2019 106 100ml 500mg 900mg/97 0.5g 100ml/8%385 5mg/343 5mg/11%7.05 240mg/3.04 80mg/2.62 80mg/)6.08 240mg/14%136 250mg/185.5 375mg/204.15 425mg/115 250mg/156.86 375mg/172.63 425mg/15%630 15mg/2.4 105U/3ml 490 15mg/3ml/22%585 0.5mg/445 0.5mg/24%258 10mg/156 10mg/40%1020 5mg/508 5mg/50%4.59 12.5mg/7.8 25mg/2.07 12.5mg/3.52 25mg/55%99.33 0.25g(40mg 10mg)43 150mg 150mg 200mg 10mg 57%2020-05-22 敬请参阅最后一页特别声明-22-证券研究报告 6 QALY SMR ASMR 3 IQWIBG/QALY QALYs P PBPA NHIC PBPA PBS OECD 3.2 2020 3 5 DRGs DRGs DRGs 2020-05-22 敬请参阅最后一页特别声明-23-证券研究报告 30 2016 DRGs 020004000600080001000012000DRGs1 DRGs2 DRGs3 DRGs4 DRGs DRGs DRGs DRGs1=DRGs2=DRGs3=DRGs4=3.3 ACS 2011 2012 7 Ticagrelor Brilinta 2011 2012 Clopidogrel Bisulfate Plavix 1997 2001 DrugsFDA ACS 2006 10 PLATO III 2009 3 8 III NCT00391872 Acute Coronary Syndrome,ACS 18624 A Randomised,Double-blind,Parallel Group,Phase 3,Efficacy and Safety Study of Ticagrelor Compared With Clopidogrel for Prevention of Vascular Events in Patients With Non-ST or ST Elevation Acute Coronary Syndromes(ACS)PLATO-a Study of PLATelet Inhibition and Patient Outcomes 2020-05-22 敬请参阅最后一页特别声明-24-证券研究报告 2006 10 2009 3 1 ACS 18 2 1 2 ACS 3 90mg 75mg 1 12 2 12 ClinicalTirals.gov 9.3%10.9%31 32 9.3%10.9%0.0%2.0%4.0%6.0%8.0%10.0%12.0%14.0%10.4%10.1%0.0%2.0%4.0%6.0%8.0%10.0%12.0%14.0%ClinicalTirals.gov ClinicalTirals.gov 2013 1)PLATO 2)Markov 2020-05-22 敬请参阅最后一页特别声明-25-证券研究报告 33 Markov PLATO PLATO PLATO Incremental Cost-Effectiveness Ratio,ICER:ICER=(C-C)/(Q-Q)=C/Q C Q(Quality-Adjusted Life Years,QALYs)C 0 Q0 ICER 34 35 PLATO QALY 90.3%4.5%0.9%4.3%88.5%5.2%0.8%5.4%0%10%20%30%40%50%60%70%80%90%100%0.87 0.82 0.74 0.24 0.88 0.81 0.73 0.25-0.010-0.005 0.000 0.005 0.010 0.015 0.020 0.0 0.2 0.4 0.6 0.8 1.0 QALY QALY Q PLATO EQ-5D 2020-05-22 敬请参阅最后一页特别声明-26-证券研究报告 2010 36 17782 36074 16635 20798 18733 33547 23638 22152-951 2527-7003-1354-10000-5000 0 5000 10000 15000 20000 25000 30000 35000 40000 C Markov QALY 0.1117 1574 ICER=1574/0.1117=14094/QALY WHO ICER GDP GDPICER3 GDP 2010 GDP 76074-ICER-9 Markov-ICER 55400 53826 1574 14094 QALY 8.2304 8.1187 0.1117 2020-05-22 敬请参阅最后一页特别声明-27-证券研究报告 3.4 19 2019 85%2011 PR 12 RNA Sustained Virologic Response,SVR12 2011 Direct-acting Antiviral Agent,DAA SVR12 90%DAA 2018 1b 1b GT1b DAA 52-70%91-99%DAA SVR12 1%93/1%SVR12 PEG-2a 325/1%SVR12+37 GT1b 38 GT1b DAA 5.9 5.2 11.8 7.1 5.8 4.3 4.8 0%20%40%60%80%100%120%0 2 4 6 8 10 12 14()SVR12%236 93 1633 551 256 536 325 2992 1157 688 0 500 1000 1500 2000 2500 3000 3500 1%SVR12(PE G-2a)1%SVR12(PE G-2b)1%24 SVR24 1%24 SVR24 DAA 90%SVR12 PR 2019 2020-05-22 敬请参阅最后一页特别声明-28-证券研究报告 3.5 A A Hemophilia A HA X VIII FVIII quality of life,QoL HA FVIII FVIII HA 25%30%QoL HA Immune Tolerance Induction,ITI ITI HA bypassing agents,BPA activated Prothrombin Complex Concentrates,aPCC FVII recombinant activated FVII,rFVIIa/Emicizumab/HEMLIBRA VIII A VIII FVIII 39 12 FVIII ABR 40 ABR 0 20 40 60 80 100 ABR0%ABRABR0%ABRABR0%ABRABR0%ABRABR0%ABR 01020304050607080ABR 0%ABR DrugsFDA ABR=annualised bleeding rate DrugsFDA ABR=annualised bleeding rate 2020-05-22 敬请参阅最后一页特别声明-29-证券研究报告 Paolo Angelo Cortesi 1)BPA rFVIII NHS National Health Service BPA 28.7 BPA 7.9 2.9 rFVIII 2.0 ITI 3.0 2)ITI 0.08%2.30%aPCC 462,820 3)2.6 BPA 3.9 DRG 137.4 10 aPCC 1.22/IU 1.113/IU 81 IU/kg 70 IU/kg 2 rFVIIa 0.971/g 0.588/g 90/kg 90 g/kg 3 127.30/mg 77.13/mg 3.0 mg/kg 4 1.5 mg/kg aPCC 57.69%rFVIIa 30.77%aPCC+rFVIIa 11.54%rFVIII 1.072/IU 0.68/IU 50 IU/kg 3 50 IU/kg 1 130 IU/kg Paolo Angelo Cortesi Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors aPCC rFVIIa QALY 24.49 BPA QALYs 23.55 1,216/rFVIIa 3,743/rFVIIa aPCC 2520 1998 aPCC ICER-2126 rFVIIa ICER-2527 2020-05-22 敬请参阅最后一页特别声明-30-证券研究报告 41 QALY 42 aPCC rFVIIa ICER 0 23.0 23.2 23.4 23.6 23.8 24.0 24.2 24.4 24.6 0510152025303540 aPCC rFVIIa QALYs 00.20.40.60.81-30-25-20-15-10-50 vs.aPCC vs.rFVIIa()ICER/QALY Q AL Ys Paolo Angelo Cortesi Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors aPCC=activated prothrombin complex concentrates rFVIIa=recombinant activated factor VII VII Paolo Angelo Cortesi Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors aPCC=activated prothrombin complex concentrates rFVIIa=recombinant activated factor VII VII 170 HA 2019 34 2021 77 BPA 43 44 0%10%20%30%40%50%60%70%80%90%100%2019 2020 2021rFVIII ITI+rFVIIa ITI+aPCC ITIrFVIIa aPCC rFVIIa aPCC 0%10%20%30%40%50%60%70%80%90%100%2019 2020 2021 rFVIII ITI+rFVIIa ITI+aPCC ITIrFVIIa aPCC rFVIIa aPCC Paolo Angelo Cortesi Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors Paolo Angelo Cortesi Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors 2019 800 2020 1760 2021 1980 2019 2021 4540 2020-05-22 敬请参阅最后一页特别声明-31-证券研究报告 45 0204060801001201401602019 2020 2021 2019 2020 2021 rFVIII ITI rFVIIa ITI aPCC ITI rFVIIa aPCC rFVIIa aPCC Paolo Angelo Cortesi Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors aPCC rFVIIa NHS HA 4 4.1 Steven M.Paul 2010 Nature Reviews Drug Discovery 13.5 8.73 17.78 11 I II III 80%75%85%69%54%34%70%91%1 WIP 24.3 19.4 14.6 12.4 8.6 4.6 1.6 1.1 1/WIP 1 2.5 10 5 15 40 150 40 1 1.5 2 1 1.5 2.5 2.5 1.5 13.5 1 24 49 146 62 128 185 235 44 873 3%6%17%7%15%21%27%5%11%1 94 166 414 150 273 319 314 48 1778 Steven M.Paul How to improve R&D productivity:the pharmaceutical industry s grand challenge WIP=Work In Process 2020-05-22 敬请参阅最后一页特别声明-32-证券研究报告 Vinay Prasad JAMA Internal Medicine 10 6.480 10 Cabozantinib 10%10 12.4 17.9 109.1 220.7 12 FDA%Pharmacyclics 2013/11 4 7.6 328.1 1.3 222.8 1.5%215 Medivation 2012/8 2 7.0 473.3 4.0 210.7 2.2%140 Alexion Pharmaceuticals 2007/3 3 15.2 817.6 8.8 129.9 6.3%Ponatinib Ariad Pharmaceuticals 2012/12 3 5.9 480.1 4.1 54.6 8.8%52 Incyte Corporation 2011/11 5 7.8 1097.8 5.1 22.5 48.8%Pralatrexate Allos Therapeutics 2009/9 3 6.8 178.2 3.0 3.0 58.5%Spectrum 2.053 Merrimack Pharmaceuticals 2015/10 5 5.8 815.8 1.3 10.7 76.6%Talon Therapeutics 2012/8 4 6.3 157.3 0.8 2.0 77.1%Spectrum 2.033 Brentuximab vedotin Seattle Genetics 2011/8 3 10.6 899.2 5.3 10.3 86.9%Cabozantinib Exelixis 2012/11 11 8.8 1950.8 4.1 3.4 570.6%Vinay Prasad,MD,MPH Research and Development Spending to Bring a Single Cancer Drug to Market and Revenues After Approval 2020-05-22 敬请参阅最后一页特别声明-33-证券研究报告 4.2/46 CLL/SLL CLL=Chronic lymphocytic leukemia SLL=Small lymphocytic lymphoma/Ofatumumab 2020-05-22 敬请参阅最后一页特别声明-34-证券研究报告 47/CLL/SLL Ofatumumab 48 CLL/SLL DrugsFDA DrugsFDA 49 obinutuzumab CLL/SLL obinutuzumab 50 BR CLL/SLL BR DrugsFDA DrugsFDA 51 2006891251189326153411754183225733590467401000200030004000500060007000800090002014 2015 2016 2017 2018 2019 2020-05-22 敬请参阅最后一页特别声明-35-证券研究报告 5 1.1949-1996 a)1949-1984 b)1984-1996 2.1996-2009 a)1996-1998 b)1998-2000 c)2000-2009 3.2009-2015 4.2015 a)b)c)2015 2020-05-22 敬请参阅最后一页特别声明-36-证券研究报告 ICER=C/Q ICER 1)C 2)Q QALY 3 1 First/Best-In-Class First/Best-in-Class Only-in-Class Q C 2 First-Follow me-too Q ICER C First-Follow 3 6 1 2 3 万得资讯2020-05-22 敬请参阅最后一页特别声明-37-证券研究报告 6-12 15%6-12 5%15%6-12-5%5%6-12 5%15%6-12 15%A 300 1996 1266 1 48 2 2 6 17 6011 NEO A 17