20231214_西南证券_医药行业专题报告A药物催化阿尔兹海默症诊疗领域变革_66页.pdf

西南证券研究发展中心 2023 年12 月 分析师：杜向阳 执业证号：S1250520030002 电话：021-68416017 邮箱：医 药行 业 专 题报 告 A 药物催化阿尔兹海默症 诊疗领域变革 Alzheimers disease,AD WHO AD 60%-70%A T au 2018 5000 2050 2.42 AD Frost&Sullivan AD 2025-2030 1950 CAGR 4.7%AD A Aducanumab FDA A CMS A Medicare FDA Medicare FDA NIH Medicare Biogen A lecanemab FDA Medicare AD AD AD AD 2023 6 AD 20 GemVax&Kael Co Ltd III 1 CAD-106 II 8 I 6 AD PET CSF AD AD 2030 AD 180 AD AD CDMO Frost&Sullivan 2017-2021 CDMO 99 177 15.5%2030 679 2017-2021 CDMO 57.9%2030 853 AD AD AD 1 1 1.1 AD 1.2 2 2.1 2.2 AD 2.3 1L 2.4 A 2.5 AD 3 3.1 AD AD 3.2 AD 4 AD CDMO 4.1 AD 4.2 CDMO 4.3 AD CDMO 5 6 2 2023-2030:2021 AD 3.2 1 WHO 2023 2021 65 7.6 2050 16 2018 3310 2050 2.42 AD 2021 2021 1 152 126 AD 2022 AD 60%AD 1.1 AD 2016-2030E 3 Frost&Sullivan 2022 Frost&Sullivan 2020 AD 1250 AD 2025-2030 1950 4.7%1990 AD 10 20 5 2019 AD 788.3/10 23.3/10 AD PDB 2023 H1 AD 44%16%11%9%8%1.2 2016-2030 CAGR AD 4 5 1 1.1 AD 1.2 2 2.1 2.2 AD 2.3 1L 2.4 A 2.5 AD 3 3.1 AD AD 3.2 AD 4 AD CDMO 4.1 AD 4.2 CDMO 4.3 AD CDMO 5 6 WHO 2023 Alzheimers disease facts and figures 2.1 Alzheimers disease,AD WHO 60%-70%AD 12 AD AD AD MCI AD AD AD 6 Tau Scheltens P,Blennow K,Breteler M M B,et al.Alzheimers diseaseJ.The Lancet,2016,388(10043):505-517.Francis P T,Palmer A M,Snape M,et al.The cholinergic hypothesis of Alzheimer s disease:a review of progressJ.Journal of Neurology,Neurosurgery&Psychiatry,1999,66(2):137-147.Cortellis A A AD A APP APP BACE sAPP sAPP-secretase A1-42 A1-40 A AD Aducanumab lecanemab Donanemab A AD A AD(AChE)(ChAT)(Ach)2023 1 141 AD 15 Tau Tau AD T au AD T au AD 2023 7 tideglusib saracatinib nilotinib 2.2 AD AD(A)Tau 7 NICE dementia guideline:Dementia:assessment,management and support for people living with dementia and their carers.2018 July.2018 2020(ChEIs)/2018 NICE AD 2019 2020 5-AD AD 2020 4391 AD 31 AD n=344 1 2 MMSE0 25.64%MMSE4 48.71%2.3 1L AD(2020)8 Aducanumab Aduhelm 2021 6 FDA FDA 2003 AD-AD-A IgG1 AD A AD III EMERGE 18 22%ENGAGE ARIA-E 35.2%362 26%96 2022 4 Aduhelm ARIA MRI MRI ARIA 2022 4 CMS A Medicare FDA Medicare FDA NIH Medicare CMS Medicare 2022 Aducanumab 480 Aducanumab III Biogen FDA Sevigny J,Chiao P,Bussire T,et al.The antibody aducanumabreduces A plaques in Alzheimers disease.Nature.2016;537(7618):50-56.doi:10.1038/nature19323 2.4.1 Aducanumab FDA A 2.4 A 9 Lecanemab Leqembi 2003 FDA AD A 1 IgG1 A A 2023 1 6 FDA 2023 6 9 FDA III Clarity AD Lecanemab AD Lecanemab 2023 7 FDA 2022 12 22 Lecanemab III III Clarity AD Lecanemab 18 27%p=0.00005 AD ARIA ARIA Lecanemab 2023 1 18 1 23 2 3 2023 H1 4-9 Lecanemab 4 2023 100/Biogen CMS VHA Lecanemab III Biogen van Dyck CH,Swanson CJ,Aisen P et al.Lecanemab in Early Alzheimers Disease.N Engl J Med.2023 Jan 5;388(1):9-21.van Dyck CH,Swanson CJ,Aisen P,et al.Lecanemab in Early Alzheimers Disease.N Engl J Med.2023;388(1):9-21.2.4.2 Lecanemab III FDA 2.4 A 10 Donanemab A A N 3 N3pG-A IgG1 N3pG-A AD 2023 5 TRAILBLAZER-ALZ 2 III Donanemab AD NDA III TRAILBLAZER-ALZ 2 Donanemab iADRS 1182 Tau iADRS 35%CDR-SB 36%1736 AD iADRS 22%CDR-SB 29%Donanemab 18 84%1%Donanemab 2023Q2 FDA 2023 10 31 CDE III III John R.Sims,Jennifer A.Zimmer,et al Donanemab in Early Symptomatic Alzheimer Disease:The TRAILBLAZER-ALZ 2 Randomized Clinical Trial JAMA.2023;330(6):512-527 MarketWatch 2.4.3 Donanemab III NDA 2.4 A 11 ClinicalTrails 2.4 A 12 CMS 2022(CMS)aducanumab CMS CMS AD CMS AD FDA 209 83%FDA CMS AD AD 2033 2050 AD 2.4 AD 2.4.4 CMS Aducanumab CMS AD CMS AD 2.4 A 13 ClinicalTrails 2021 CFAN 1000 75.7%ADAS-cog(AChEI)()AD-AD 202 12 400ug/d vs-4.56 vs+0.8 3%vs 3%AD 92 24 4mg/d vs-4.2 vs-2.2 9%vs 3%AD 120 26 3mg/d vs-4.74 vs+0.2 14%vs 13%1059 24 4.6mg/d vs-7%vs 7%AD 396 24 24mg/d-1 vs-0.5-N-d-NMDA AD 3004 16 20mg/d vs-0.34 vs-0.15-AD 242 24 900mg vs 600mg vs-2.58 vs-1.39 vs-1.45 14.3%vs 5.9%vs 3.5%+AD 3402 16 vs ChEI-0.2 vs-0.16-2.4.5 2.4 A 14 2.5.1 药 哌齐 为 尔兹 选药 获 药 2.5 AD 药 赛 风 药 药 发齐头 进 药 证*2023 11 5-HT2A receptor;D2 receptor;5-HT1A receptor 5-HT1A receptor;5-HT2A receptor;D2 receptor Lundbeck;Otsuka 2015 JP 2 2022.12 I I 2 AMPA receptor;AMPA receptor I.S.F.;Ciba-Geigy(Novartis)II 2020.1 NA NA;III 2019.11 3 AChE;BuChE AChE;BuChE Novartis 2017.7 JP 1998.5 EU/JP/US 2023.10 2000.6+receptor;NMDA receptor;5-HT3 receptor;nAChR receptor;D2 receptor;AChE NMDA receptor;5-HT3 receptor;nAChR;D2 receptor receptor;AChE Forest Laboratories(AbbVie)2014.12 2 vitamin B6 vitamin B6 Merck&Co.2014.10 3 NMDA receptor;5-HT3 receptor;nAChR;D2 receptor NMDA receptor;5-HT3 receptor;nAChR;D2 receptor Merz Pharma;Eli Lilly;Lundbeck;Daiichi Sankyo;Forest Laboratories(AbbVie)2003.10 EU/JP/US 2012.7 3 nAChR;AChE AChE;nAChR Johnson&Johnson 2002.4 EU/JP/US NA NA Italfarmaco 1999.12 receptor;AChE;AChE Eisai 1996.11 EU/JP/US 1999.1 AChE AChE;Biscayne Neurotherapeutics(Supernus Pharmaceuticals)1993.8 EU/JP/US II 2 MAO-A;MAO-B MAO-A;MAO-B Mitsubishi Tanabe Pharma;Eisai 1987 JP Alpha-1062 cholinesterase cholinesterase Alpha Cognition 3 1 2 3 15 AChE;BuChE AChE;BuChE III III Tau Tau TauRx Pharmaceuticals III AR1001 PDE5 PDE5 AriBio III PM012 NA Mediforum;PuriMED;VT BIO III Taisi NA III+NA;COX NA;COX AZTherapies III tertomotide TERT GemVax&Kael III PDE5 PDE5 Dong-A Pharma;Mezzion Pharma III+2 receptor;NMDA receptor;NET;nAChR;CYP2D6;SERT;DAT NMDA receptor;5-HT;nAChR;CYP2D6 Axsome Therapeutics III 2 CB2;CB1 CB1;CB2 MEDA(Viatris)III c-Kit;CSF-1R;Bcr-Abl;PDGFR c-Kit;PDGFR;CSF-1R;Bcr-Abl Novartis;KeifeRx III 3 OX1R;OX2R OX1R;OX2R Merck&Co.III Lyn;c-Kit;CSF-1R;SARS-CoV-2 3CLpro;PDGFR c-Kit;PDGFR;CSF-1R;Lyn;SARS-CoV-2 3CLpro AB Science III HE3286 ERK;NF-NF-;ERK Harbor BioSciences;Neurmedix(BioVie)III azeliragon RAGE RAGE Cantex Pharmaceuticals;vTv Therapeutics;Pfizer III masupirdine2 5-HT6 receptor 5-HT6 receptor Suven Life Sciences III sumifilam FLNA FLNA Cassava Sciences III III3 valiltramiprosate Bellus Health(GSK);Alzheon III NA NA Cerecin III NMDA receptor NMDA receptor Otsuka;Sun Pharmaceutical III 1 2 3 数据来源：医药魔方，西 南证券 整理*注：数据截至2023 年11 月 2.5.1 化药：多奈哌齐为 阿尔 兹海 默病 患者 首选 药物，获 批药 物机 制有 限 2.5 AD 药 物 赛道风起云涌，化 药、生物药研 发齐头并进 16 数据来源：医药魔方，西 南证券 整理*注：数据截至2023 年11 月+2 NMDA receptor;sodium channel sodium channel;NMDA receptor Otsuka;Sun Pharmaceutical III SIRT1 SIRT1 Jupiter Neurosciences;Sirtris Pharmaceuticals(GSK)III trigriluzole EAAT2 EAAT2 Biohaven II/III(+)-AChE AChE Annovis Bio II/III blarcamesine Anavex Life Sciences II/III atuzaginstat gingipain gingipain Lighthouse;Quince Therapeutics II/III fosgonimeton c-Met c-Met Athira Pharma;University of Washington II/III piromelatine3 melatonin receptor;5-HT1D receptor;5-HT1A receptor melatonin receptor;5-HT1A receptor;5-HT1D receptor Neurim Pharmaceuticals II/III JK-50561 RAC1 NA II II Wei Li Bai NA NA II II AChE QPCTL;QPCT;II NMDA receptor;II II varoglutamstat3 QPCTL;QPCT QPCTL;QPCT;Vivoryon Therapeutics II AD101 T-type calcium channel T-type calcium channel AmyriAD II AVN-322 5-HT6 receptor 5-HT6 receptor AllaChem;Avineuro Pharmaceuticals II EX039 DAAO DAAO II IONIS-MAPTRx3 Tau Ionis Pharmaceuticals;Biogen II LY3372689 OGA OGA Eli Lilly II MW01-18-150SRM Northw estern University(USA);NeuroKine Therapeutics II NA-704 NA NA NeuroActiva II NP03 BACE1 BACE1 Medesis Pharma II PXT864 NA;GABAB receptor NA;GABAB receptor Pharnext II 1 2 3 2.5.1 药 哌齐 为 尔兹 选药 获 药 2.5 AD 药 赛 风 药 药 发齐头 进 17 数据来源：医药魔方，西 南证券 整理*注：数据截至2023 年11 月 ReS19-T NA NA reMYND II T3D-959 T3D Therapeutics;Bayer;DARA BioSciences(Biodexa Pharmaceuticals)II edonerpic NA NA Toyama Chemical(PeptiDream)II nAChR nAChR Rock Creek Pharmaceuticals II sovateltide ETB ETB Pharmazz;University of Chicago;Spectrum Pharma(Assertio Holdings,Inc.);Ciba-Geigy(Novartis)II mAChR mAChR Dr.Karl Thomae(Boehringer Ingelheim)II CB receptor CB receptor;GW Pharmaceuticals(Jazz Pharmaceuticals)II+HDAC;bile acid bile acid;HDAC Amylyx Pharmaceuticals;Neopharm(Insys Therapeutics)II 3 OX1R;OX2R OX1R;OX2R Eisai;Purdue Pharma II RPh201 NA NA Regenera Pharma II adrabetadex NA NA Vtesse(Mallinckrodt);Cloudbreak Pharma;Cyclo Therapeutics;Mandos II brilaroxazine3 D2 receptor;5-HT6 receptor;5-HT1A receptor 5-HT6 receptor;5-HT1A receptor;D 2 receptor Reviva Pharmaceuticals II dalzanemdor3 NMDA receptor NMDA receptor Sage Therapeutics II iclepertin GlyT1 GlyT1 Boehringer Ingelheim II obicetrapib CETP CETP Menarini;New Amsterdam Pharma;Mitsubishi Tanabe Pharma;Dezima Pharma(Amgen)II seltorexant OX2R OX2R Johnson&Johnson;Minerva Neurosciences II traneurocin NA NA NeuroActiva II zatolmilast PDE4D PDE4D Shionogi;Tetra Therapeutics(Shionogi)II TFEB TFEB Seelos Therapeutics II-synuclein;DYRK1A DYRK1A-synuclein;-II 1 2 3 2.5.1 药 哌齐 为 尔兹 选药 获 药 2.5 AD 药 赛 风 药 药 发齐头 进 18 数据来源：医药魔方，西 南证券 整理*注：数据截至2023 年11 月 L-NA NA Neurocentria II tideglusib GSK-GSK-AMO Pharma;Noscira II CSTC1-BAC NA II CT1812 Cognition Therapeutics II JZP5412 NA Jazz Pharmaceuticals II MK-19423 NA NA Merck&Co.II SDI-118 SV2A SV2A Syndesi Therapeutics(AbbVie);UCB II UE2343-HSD1-HSD1 University of Edinburgh;Actinogen Medical II II3 neflamapimod p38 MAPK p38 MAPK EIP Pharma(CervoMed);Kissei;Vertex Pharmaceuticals II vafidemstat KDM1A;MAO-B KDM1A;MAO-B Oryzon Genomics II zagociguat sGC sGC Ironw ood Pharmaceuticals;Tisento Therapeutics;Cyclerion Therapeutics II+CB2;NA;CB1 NA;CB1;CB2;SciSparc II NAD+NAD+ChromaDex II 1 BryoLogyx;Neurotrope(Petros Pharmaceuticals);Synaptogenix II+NA;EphA2;Lck;c-Abl;Fyn;Src;BTK c-Kit;Bcr-Abl;YES1;EphA2;Lck;Fyn;BTK;TEC;Src;Wake Forest University Health Science Center;Mayo Clinic II 2 Transition Therapeutics(Opko Health)II LM11A-31 p75NTR p75NTR University of North Carolina at Chapel Hill;PharmatrophiX I/II JAK1;JAK2 JAK1;JAK2 Eli Lilly;Incyte I/II MK-8189 PDE10A PDE10A Royalty Pharma;Merck&Co.I/II S-Ausio Pharmaceuticals I/II 1 2 3 2.5.1 药 哌齐 为 尔兹 选药 获 药 2.5 AD 药 赛 风 药 药 发齐头 进 19 数据来源：医药魔方，西 南证券 整理*注：数据截至2023 年11 月 NAD+NAD+-I/II 64Cu-FBP83 fibrin 64Cu Massachusetts General Hospital I/II LiProSal NA NA Alzamend Neuro I/II HEC30654 5-HT6 receptor 5-HT6 receptor I I OAB-14 RXR RXR;I I RP902 NA I I NA NA;I 1 I I I Tau;TRPML1;calcium channel;AChE calcium channel;NA;TRPML1;AChE;I I(-)NA NA ArcherPharmaceuticals I AAT-009 5-HT4 receptor 5-HT4 receptor AskAt I ACD856 Trk Trk AlzeCure Pharma I ACI-3024 Tau Tau Eli Lilly;AC Immune I AGN-242071 M1 receptor M1 receptor Allergan(AbbVie)I AGN-242626 M4 receptor M4 receptor Allergan(AbbVie)I BEY2153;Tau BeyondBio I BIIB113 OGA OGA Biogen I BMS-984923 mGluR5 mGluR5 Allyx Therapeutics;Bristol-Myers Squibb I BNC375 Merck&Co.;Bionomics I CMS121 FAS FAS Virogenics;Salk Institute for Biological Studies I DWP09031 Daew oong Pharmaceutical(HanAll Biopharma)I E2511 TrkA TrkA Eisai I GC021109 P2Y6 receptor P2Y6 receptor GliaCure I HTL9936 M1 receptor M1 receptor Heptares Therapeutics(Sosei);Neurocrine Biosciences;Allergan(AbbVie)I 1 2 3 2.5.1 药 哌齐 为 尔兹 选药 获 药 2.5 AD 药 赛 风 药 药 发齐头 进 20 数据来源：医药魔方，西 南证券 整理*注：数据截至2023 年11 月 ITI-1284 5-HT2A receptor;D2 receptor 5-HT2A receptor;D2 receptor Intra-Cellular Therapies I J147 mycobacterial ATP synthase mycobacterial ATP synthase Abrexa Pharmaceuticals;Salk Institute for Biological Studies I MK-4334 Merck&Co.;Bionomics I NGP 555-secretase-secretase NeuroGenetic Pharmaceuticals I ODM-102-AR-AR Orion I 1 2 3 2.5.1 药 哌齐 为 尔兹 选药 获 药 2.5 AD 药 赛 风 药 药 发齐头 进 21 数据来源：医药魔方，西 南证券 整理*注：数据截至2023 年11 月 lecanemab anti-Biogen;BioArctic;Eisai 2023.9 JP/US III aducanumab anti-Biogen;University of Zurich;Eisai;Neurimmune 2021.6 III III3 III3 donanemab pGlu3-anti-pGlu3-Eli Lilly 2021.10 2023.10 remternetug pGlu3-anti-pGlu3-Eli Lilly III III GLP-1RA GLP-1R Novo Nordisk III III crenezumab anti-Genentech(Roche);AC Immune III III E2814 Tau anti-Tau University College London;Eisai II/III amilomotide Novartis II/III posdinema Tau anti-Tau Johnson&Johnson II I AADvac1 Tau Tau Axon Neuroscience II ABBV-916 pGlu3-anti-pGlu3-AbbVie II ABvac40 Araclon Biotech II AL-101 SORT1 anti-SORT1 GSK;Alector II AL002 TREM2 anti-TREM2 Alector;AbbVie II UB-311 Vaxxinity;United Biomedical II semorinemab Tau anti-Tau Genentech(Roche);AC Immune II itMSC3 NA Stemedica Cell Technologies II TNFR2 TNFR2-Fc Pfizer;Immunex(Amgen);Takeda Pharmaceuticals;Genentech(Roche)II GM-CSF GM-CSF Partner Therapeutics;Genzyme(Sanofi)II-2 IL-2 IL-2-II latozinemab3 SORT1 anti-SORT1 GSK;Alector II pegipanermin TNF-TNF-Inmune Bio II AKST/GRF6019 NA NA Alkahest(Grifols);Grifols II 1 2 3 2.5.2 药 AD 药风 2.5 AD 药 赛 风 药 药 发齐头 进 22 数据来源：医药魔方，西 南证券 整理*注：数据截至2023 年11 月 AstroStem NA RNL Bio;Nature Cell II Coya 301 IL-2 NA Coya Therapeutics;ARScience Bio II Lomecel-B NA Longeveron II TB006 galectin-3 anti-galectin-3 Truebinding II bepranemab Tau anti-Tau UCB;Roche II ACI-35.030 Tau Tau Johnson&Johnson;AC Immune I/II AL002 Alzamend Neuro;University of South Florida I/II JACI-35.054 Tau Tau AC Immune;Janssen Biotech(Johnson&Johnson)I/II Neurostem NA Medipost I/II trontinemab anti-;anti-TfR1 Roche I/II ACI-24 AC Immune I/II HB-adMSCs NA Hope Biosciences I/II pepinemab SEMA4D anti-SEMA4D Vaccinex I/II SHR-1707 A anti-A I AAV2-BDNF BDNF University of California,San Diego I ACI-35 Tau Tau Johnson&Johnson;AC Immune I ACU193 anti-Acumen Pharmaceuticals I AL003 CD33 anti-CD33 Alector I ALZ-101 Alzinova I APNmAb005 Tau anti-Tau I AV-1959D1 Nuravax;IMM I BIIB076 Tau anti-Tau Biogen;Neurimmune I E2025 EPHA4 anti-EPHA4 Eisai I IBC-Ab002 PDL1 anti-PDL1 ImmunoBrain Checkpoint I KHK6640 anti-Kyow a Kirin I 1 2 3 2.5.2 药 AD 药风 2.5 AD 药 赛 风 药 药 发齐头 进 23 数据来源：医药魔方，西 南证券 整理*注：数据截至2023 年11 月 LX1001 ApoE2 LEXEO Therapeutics;Weill Cornell Medical College I Lu AF87908 Tau anti-Tau Lundbeck I MEDI1814 anti-Eli Lilly;AstraZeneca I MER5101 Mercia Pharma I MK-2214 Tau anti-Tau Merck&Co.I PRX012 anti-Prothena I RB-ADSC NA Regeneration Biomedical I VT301 NA Treg VT BIO I NA NA Brigham and Womens Hospital;Inspirevax;Biodextris I GLP-1R GLP-1R Novo Nordisk I ANX005 C1q anti-C1q Annexon Biosciences I SNK01 NA NK NKGen Biotech I BMS-986446 Tau anti-Tau Bristol-Myers Squibb;Prothena I THN391 fibrin anti-fibrin Therini Bio I 3 anti-Biogen;BioArctic;Eisai GX-G6 GLP-1R GLP-1R;GLP-1-Fc;Genexine BX U001 NA ZT002 GLP-1R GLP-1R ADEL-Y01 Tau anti-Tau ADEL;Oscotec foralumab anti-Light Chain Bioscience;Tiziana Life Sciences;Prometheus Biosciences(Merck&Co.);Merck KGaA pegsebrenatide GLP-1R GLP-1R Neuraly SB623 NA;SanBio;Sumitomo Pharma ARG-007 NA NA Argenica 1 2 3 2.5.2 药 AD 药风 2.5 AD 药 赛 风 药 药 发齐头 进 24 数据来源：医药魔方，西 南证券 整理*注：数据截至2023 年11 月 2 NA NA()2020.10 NA NA III NA NA II NA NA II NA;II NA NA-II BII NA;1 2 3 2.5.3 药 创 药 发 处 II 临 阶 2.5 AD 药 赛 风 药 药 发齐头 进 25 26 1 1.1 AD 1.2 2 2.1 2.2 AD 2.3 1L 2.4 A 2.5 AD 3 3.1 AD AD 3.2 AD 4 AD CDMO 4.1 AD 4.2 CDMO 4.3 AD CDMO 5 6 3 AD AD AD AD AD 27 3.1 AD AD 2023 6 AD 20 GemVax&Kael Co Ltd III 1 CAD-106 II 8 I 6 TERT GemVax&Kael Co Ltd ALZN-002 Alzamend Neuro Inc II ALZ-101 Alzinova AB I Protollin Biodextris Inc;The Brigham and Womens Hospital Inc;I ABvac40 Araclon Biotech Sl II ACI-35.030 MAPT AC Immune SA;II JACI-35.054 MAPT AC Immune SA;II ACI-24.060 AC Immune SA II UB-311 United Biomedical Inc II AADvac1 MAPT Axon Neuroscience SE II CAD-106 Abeta III ACI-35 MAPT ACImmune SA;I-secretase Elan Corp plc;W