20240301_平安证券_医药行业：高尿酸血症和痛风行业全景图国内千万痛风患者群体亟待“疗效佳安全优”新药_45页.pdf

2024 03 01:S1060514100001 YEYIN757PINGAN.COM.CN:S1060519060002 HANMENGMENG005PINGAN.COM.CN 1 13.3%1.77 1.1%1466 8000 2021-2022 2023 20 FDA FDA 2013 URAT1 IL-90%URAT1 90%2024 2 20 URAT1 SHR4640 XNW3009 YL-90148 ABP671 IL-1 IL-SSGJ-613 ZXFUvMqNoNqRoQmPmRsNpOaQbP9PmOmMoMmQiNmMpMjMmMsP8OrRvNNZoNtMxNoMtP C O N T E NT S2 1 3 4 25 6 Hyperuricemia,HUA HUA 2 420umol/L 360umol/L 2 420umol/L 1/2 3 HUA Gout:Risk Factors,Diagnosis and Treatment 4 urate-lowering therapy,ULT ULT treat-to-target T2T 360umol/L 300umol/L MSU 5HUA 1 1 2 3 xanthine oxidase,XOD 1/3 2/3 XOI 6 XO HUA 1 Allopurinol xanthine oxidase XOD)xanthine oxidase inhibitor XOI Febuxostat XOI 2008 4 2009 2 FDA 2013 4 FDA(Topiroxostat)XOI 2013 6 XOD 100%Recent studies on the natural products with xanthine oxidase inhibitory effect 7HUA 1 8 Sebela Ireland XOI1966 1973 2002 2009 50mg/1-2 50-100mg-1 200-300mg 2-3 2 600mg 6 100mg/XOI2008 2009 2011 2013 2017 2020 20mg/4 sUA 20mg 80mg sUA 6mg/dL 20mg 40mg FDA XOI2013 20mg sUA 60mg 80mg 2 20mg HUA 1 Tigulixostat 2022 9550 LG Tigulixostat Tigulixostat 10-800mg 7 sUA Tigulixostat 2022 Q4 2022 9550 6.6 IBI-128 LG 1000 8550 MCE 9 Tigulixostat 2022 10 350 100mg 200mg 300mg 100mg+200mg 6 66 4 5 6 sUA 6mg/dL 2022 10 2542 100mg 200mg 300mg 100mg+200mg 6 100-800mg 3 12 100mg 80mg12 4 5 6 sUA 6mg/dL Tigulixostat Tigulixostat HUA 1 Tigulixostat Tigulixostat 2019 10-2021 5 42 50mg 100mg 200mg Tigulixostat 12 12 sUA5mg/dL 143 50mg n=34 100mg n=38 200mg n=37 n=34 12 sUA5mg/dL 47.1%44.7%62.2%2.9%sUA-38.8%-61.8%Tigulixostat 9.4%13.2%50%56.8%50mg/100mg/200mg/26.5%/15.8%/27%/17.6%Serum Urate Lowering Efficacy and Safety of Tigulixostat in Gout Patients With Hyperuricemia:A Randomized,Double-Blind,Placebo-Controlled,Dose-Finding Trial 10Tigulixostat Tigulixostat HUA 2 1 2 3 URAT1 90%9 GLUT9 1 URAT1 4/10 organic anion transotter,OAT 4/10 OAT1/2/3 4 MRP4 G2 ABCG2 1/4 NPT 1/4 URAT1 90%,TAKAHASHI CLINIC 11 URAT1 HUA 2 Benzbromarone 1971 URAT1 Labaz 1994 2000 FDA 2003 2006 EULAR 2000 Lesinurad 2015 12 FDA FDA URAT1 2015 2 FDA 2019 400mg/200mg/FDA 200mg/2012 6 12.6 Ardea Biosciences Dotinurad 2020 4mg 58 sUA=6mg/dL 100%2024 1 CDE 12HUA 2 13 URAT1 URAT1 1983 1971 2003 2003 FDA 50mg 1 1-3 sUA 14 50-100mg 1-2 50mg FDA URAT1 AZ2015 2016 200mg 1 200mg200mg 400mg 200mg/FDA 200mg+300mg URAT1+XO AZ2017 2018 URAT1Fuji Mochida Pharmaceutical;Fortress Biotech2020 2024 1 CDE 0.5mg 1 sUA 2mg 4mg0.5mg 1mg 2mg 0.5mg 60%HUA 3 1 2 3 14 2020/2021/2022/Rasburicase UO2001 2 2002 72009 10 2018 10 1.687 1.772 1.863Peglopticase UO2010 92013 1 SavientPharmaceuticals Amgen 4.059 5.655 7.162 UO C O N T E NT S2 1 3 4 155 6 2020 9.8 2030 14.2 2020 1.8 2030 2.4 13.3%1.1%1500/1602468101214162016 2017 2018 2019 2020 2021 2022 2023E 2024E 2025E 2026E 2027E 2028E 2029E 2030E/2015 26 2019 32 2024 33 2 2023 20 Frost&Sullivian 172628303332252729313337424958677779142328272320 202229415878951080204060801001202015 2016 2017 2018 2019 2020 2021 2022 2023E 2024E 2025E 2026E 2027E 2028E 2029E 2030E/20-30 2020 40mg 16 16.48 40mg 10 15.16 40mg 12 19.79 40mg 10 1 2020 4 2021 1.07 PDB 18/2020 2021 2022 2023Q1-Q3Teijin 77 25 28 25 22424 2831 2669 1967 17057 7842 8095 6249 41 6 0.7 0.3 0.1 39558 10698 10792 8289/2020 2021 2022 2023Q1-Q3 6 61 61 100 14 29 41 1 23 18 40 6 97 163 405 290 2587 2431 2188 1461 2727 2702 2734 1857/2020 2021 2022 2023Q1-Q3 939 907 2146 580 Torrent pharmaceuticals6918 7032 6668 4214 16 334 7857 7939 8814 4795/2020 2021 2022 2023Q1-Q3 109 56 66 60 115 231 227 182 223 286 293 242/2022/C O N T E NT S2 1 3 4 195 6 URAT1 2024 2 21 URAT1 URAT1 SHR4640 YL-90148 XNW3009 ABP-671 20 HR091506 NA III III SHR4640 URAT1 III III XNW3009 URAT1 III II/III YL-90148 URAT1 III III epaminuradURAT1 C&C Research Labs.;Chugai Pharmaceutical III I;COX;III III ABP-671 URAT1 II/III II/III AC-201 IL-1;URAT1 TWi Biotechnology II II AR882 URAT1 Arthrosi Therapeutics;II II D-0120 URAT1 II II HP501 URAT1 II II SAP-001 URAT1;II I THDBH130 URAT1;II II WXSH0493 URAT1 II II URAT1 II II FCN-207 URAT1 I I FCN-342 URAT1 I I HEC93077 NA I I QJ-19-0002 URAT1 I I THDBH151 XO;URAT1 I I uPA;Redhill Biopharma;Heidelberg Pharma URAT1 CYP2C9 6-P450s AR882-OH Google patent 21 XNM3009 AR882 ABP671 URC102 URAT1 FDA 2015 URAT1 OAT4 200-600mg 200mg URAT1 SHR4640 YL-90148 D-0120 HP501 Google patent Recent advances in gout drugs 22 D-0120 HP501 SHR4640 YL-90148 URAT1 23 SHR4640 2021 7 780 SHR4640 1mg 7 2.5mg 7 5mg 14 10mg 84 10mg 336 16 sUA360umol/L XNW3009 2022 10 850 0.25mg XNW3009,QD;0.5mg XNW3009,QD 20mg QD 1 sUA360umol/L 2 18 sUA360umol/L YL-90148 2022 12 714 YL-90148 16 20 24 sUA360umol/L Epaminurad JW Pharmaceutical 2023 4 588 6mg 9mg Epaminurad 40mg 80mg 24 sUA360umol/L ABP671 2023 12 875 2mg 4mg 6mg 20mg 40mg 16/28 sUA360umol/L 2023 4 580 ABP671 28 sUA360umol/L AR882 2024 URAT1 URAT1 700 sUA 360umol/L 2021 7 2022 10 2022 12 2023 3 2023 12 12 AR882 2024 URAT1 URAT1 24 SHR4640 198 1 1 1 1 1 2.5mg 5mg 10mg SHR4640 50mg 5 sUA=360umol/L 6mg/dL 5mg SHR4640 10mg SHR 4640 5 sUA=360umol/L 32.5%/72.5%/61.5%/0ABP671 a 60 Group1 2mg QD 1mg BID Group2 4mg QD 2mg BID Group3 8mg QD 4mg BID ABP-671 4 sUA 4 2mg 4mg 8mg sUA 36%51%59%7%1%13%XNW3009 150 0.25mg XNW3009,QD;50mg QD10 sUA=360umol/L 6mg/dL sUA=360umol/L 72%vs 51.9%AR882&Arthrosi 42 AR882 75mg AR882 50mg 24 3 sUA 5mg/dL 3 AR882 75mg AR882 50mg+sUA 49.6%/49.9%/34.9%75mg AR882 86%64%sUA6mg/dL 5mg/dL 140 AR882 50mg AR882 75mg 12 6 sUA 6mg/dL 12:1 75mg 89%82%63%29%6 5 4 3mg/dL 2 50mg 78%50%8%6 5 4mg/dL 3 URAT1 sUA=360umol/L 10mg SHR 4640 5 sUA=360umol/L 72.5%61.5%0.25mg XNW3009 10 sUA=360umol/L 72%51.9%sUA 2mg 4mg 8mg ABP671 sUA 36%51%59%7%1%13%AR882 sUA6 5 4 3mg/dL AR882 50mg 75mg URAT1 SHR4640 SHR4640 2019 SHR4640 3 2022 SHR4640 FOCUS SHR4640 HUA 5 sUA=360umol/L 5 360mol/L 5mgSHR4640 32.5%10mgSHR4640 72.5%61.5%5mg 10mgSHR4640 5 360mol/L 10mgSHR4640 sUA 72.5%vs61.5%Efficacy and safety of a selective URAT1 inhibitor SHR4640 in Chinese subjects with hyperuricaemia:a randomized controlled phase II study SHR4640 25SHR4640 XNW3009 XNW3009 2024 2 XNW3009 1 sUA360umol/L 2 18 sUA360umol/L XNW3009 XNW3009 XNW3009 XNW3009 XNW3009 CYP CYP/XNW3009 II 0.5mg 72%360umol/L 50mg 51.9%360umol/L XNW3009 12 IC50 URAT1 40 26 ABP-671 ABP-671 URAT1 sUA 60 Group1 2mg QD 1mg BID Group2 4mg QD 2mgBID Group3 8mg QD 4mg BID ABP-671 sUA 8 mg/dL APB-671 sUA 6mg/dL ABP-671 sUA 4 6 ABP-671 sUA 3.1 5.3mg/dL 9.1mg/dL ABP-671 4 2mg 4mg 8mg sUA 36%51%59%7%1%13%p0.0001 54 6 7 ABP-671 2 1mg 86%sUA 6mg/dL)100%6 mg/dL 6mg 12mg 100%sUA 5mg/dL 300 sUA 4 mg/dL(240 57%100%27 ABP-671 A Double-Blind Ascending Dose Placebo-Controlled Phase 2a Study of ABP-671,a Novel,Potent and Selective URAT1 Inhibitor,in Patients with Gout or Hyperuricemia 28 ABP-671&Arthrosi AR882 2b 12 140 AR882 10 AR882 50mg AR882 75mg 12 2 sUA sUA 6 5 4 3mg/dL 12 sUA 8.6mg/dL 75mg 3.5mg/dL 50mg 5.0mg/dL 12 75mg 89%82%63%29%6 5 4 3mg/dL 50mg 78%50%8%6 5 4mg/dL 8 12 sUA AR882 12 65 A 12-week randomized double-blinded placebo-controlled phase 2b study of safety,tolerability and efficacy of AR882 in gout patients sUA 29&Arthrosi AR882 2023 ACR AR882 6 1 1 1 42 sUA 9.1-9.6mg/dL AR882 75mg AR882 50mg+300mg 4 6 6 DECT 3 sUA sUA 3 AR882 75mg AR882 50mg+sUA 49.6%/49.9%/34.9%75mg AR882 86%64%sUA6mg/dL 5mg/dL DECT DECT 6 DECT-0.9cm3-1.2cm3 AR882 75mg-8.3cm3 sUA 30 6 DECT D-0120 D-0120 D-0120 D-0120 80%1 2/3 2023 4 D-0120 D-0120 31 D-0120 2022 8 121 1 1mg D-0120 2 12 2 A 1 2 1mg D-0120 2 3-12 2mg 2 B 1 2 1mg D-0120 2 3 2mg 2 5 50mg 1 12 12 sUA360umol/L 2022 12 80 A D-0120 2-12 D-0120 B D-0120 2 D-01203-12 D-0120 12 sUA360umol/L HP501 HP501 URAT1 2037 HP501 HP501 Cmax 2018 HP501 2023 12 FDA 2024,01 HP501 32HP501 URAT1 THDBH130 2021 6 THDB130/THDB131 THDB150/THDB151 1 IND 7000 2 1.305 3 6.5%THDBH130 PK/PD URAT1 THDBH130 6mg/dl 4 5mg/dl 3 3 33 THDBH130 2.5mg 20mg/78 2.5mg 20mg 4 5-20mg/150 THDBH130 Epaminurad URC-102 URC-102 JW Pharmaceutical Corp C&C Dotinurad URC-102 Emax 46%vs 23%URC-102 vs ED50 3.2 4.5mg/kg URC-102 2019 9 JW Pharmaceutical URC-102 JWP URC-102 wind 34 EpaminuradJW Pharmaceutical 588 2023 4 6mg 9mg Epaminurad 40mg 80mg 24 sUA360umol/L 48 2021 2 SIM1909-13 URC102 6mg URC-102 C O N T E NT S2 1 3 4 355 6 IL-1 IL-1 NLRP3 IL-IL-IL-IL-IL-1 IL-1 The role of interleukin-1 family members in hyperuricemia and gout IL-136 IL-37 SSGJ-613 anti-IL-1 III III I/II I/II pegsiticase UOSelecta Biosciences(Cartesian Therapeutics);EnzymeRx III I anti-IL-1 III III anti-GM-CSF GR007 IL-1RA II II PJ003 UO;I/II I/II JS103 UO I I IL-IL-2023 1 302 313 12 38 2022 12 302 313 1 3 VAS 2 12 200mg 150mg/1 200mg sc 2023 8 302 1 3 VAS 2 12 200mg 2023 6 30 24 1 0.5mg/kg 2 1.5mg/kg 3 4mg/kg 4 4 2023 11 30 6 300mg 4 IL-SSGJ-613 2024 1 SSGJ-613 1b/2 1b 2 SSGJ-613 120 Ib II 89 SSGJ-613 31 SSGJ-613 II SSGJ-613 8 vs 15 VAS SSGJ-613 12 14.3%51.6%SSGJ-613 2024 1 SSGJ-613 39 2023 12 500 1 3 VAS 2 12 200mg 2022 10 120 1b 24 2 3 VAS 3 100mg 200mg 300mg 10 2 200mg 300mg 2021 8 34 PK C O N T E NT S2 1 3 4 405 6 41 C O N T E NT S2 1 3 4 425 6 -43:6 300 20%6 300 10%20%6 300 10%6 300 10%:6 300 5%6 300 5%6 300 5%2020 44:6 20%6 10%20%6 10%6 10%:6 5%6 5%6 5%2024