Cynthia Levy,Palak J Trivedi,Kris V Kowdley,Stuart C Gordon,Christopher L Bowlus,Maria Carlota Londoño,Gideon M Hirschfield,Aliya Gulamhusein,Eric J Lawitz,John M Vierling,Marlyn J Mayo,Ira M Jacobson,Andreas E Kremer,Christophe Corpechot,David Jones,Peter Buggisch,Shuqiong Zhuo,Sarah Proehl,Carrie Heusner,Charles A McWherter,Daria B Crittenden,
{"title":"选择性PPARδ激动剂Seladelpar治疗原发性胆道胆管炎的长期疗效和安全性:ASSURE中期研究结果","authors":"Cynthia Levy,Palak J Trivedi,Kris V Kowdley,Stuart C Gordon,Christopher L Bowlus,Maria Carlota Londoño,Gideon M Hirschfield,Aliya Gulamhusein,Eric J Lawitz,John M Vierling,Marlyn J Mayo,Ira M Jacobson,Andreas E Kremer,Christophe Corpechot,David Jones,Peter Buggisch,Shuqiong Zhuo,Sarah Proehl,Carrie Heusner,Charles A McWherter,Daria B Crittenden,","doi":"10.14309/ajg.0000000000003603","DOIUrl":null,"url":null,"abstract":"OBJECTIVES\r\nEvaluate interim data from the ongoing, open-label, long-term efficacy and safety ASSURE study of seladelpar, a selective peroxisome proliferator-activated receptor δ agonist, in primary biliary cholangitis (PBC).\r\n\r\nMETHODS\r\nPatients rolling over from the phase 3, randomized, placebo-controlled, 12-month RESPONSE study or with previous participation in earlier legacy seladelpar studies were enrolled. Interim evaluations included composite biochemical response (alkaline phosphatase [ALP] <1.67×upper limit of normal [ULN], total bilirubin ≤ULN, and ALP decrease ≥15%), pruritus numerical rating scale (NRS) change among patients with a baseline score ≥4, and safety.\r\n\r\nRESULTS\r\nAt interim cutoff, 337 patients were enrolled and received ≥1 seladelpar 10-mg dose; 54 placebo-treated and 104 seladelpar-treated from RESPONSE and 179 from legacy studies. The composite response rate at RESPONSE completion was 62% (79/128) with seladelpar and 20% (13/65) with placebo. After 12 months in ASSURE, response rates were 72% (21/29) in patients continuing seladelpar and 94% (15/16) in crossover seladelpar patients. In legacy trial patients, response rates were 73% (120/164) and 70% (69/99) after 12 and 24 months of treatment in ASSURE, respectively. The NRS decrease at RESPONSE completion in seladelpar-treated patients with baseline NRS ≥4 (-3.4) was maintained after 6 additional months of treatment (-3.8); changes were similar in crossover seladelpar (-3.8) and legacy patients (-3.5) after 6 months of treatment in ASSURE. No seladelpar-related serious adverse events were reported.\r\n\r\nCONCLUSIONS\r\nSeladelpar demonstrated durable improvements in cholestatic biomarkers and pruritus in patients with PBC with up to 2 years of treatment and remained overall safe with long-term use.","PeriodicalId":520099,"journal":{"name":"The American Journal of Gastroenterology","volume":"6 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Long-term Efficacy and Safety of Selective PPARδ Agonist Seladelpar in Primary Biliary Cholangitis: ASSURE Interim Study Results.\",\"authors\":\"Cynthia Levy,Palak J Trivedi,Kris V Kowdley,Stuart C Gordon,Christopher L Bowlus,Maria Carlota Londoño,Gideon M Hirschfield,Aliya Gulamhusein,Eric J Lawitz,John M Vierling,Marlyn J Mayo,Ira M Jacobson,Andreas E Kremer,Christophe Corpechot,David Jones,Peter Buggisch,Shuqiong Zhuo,Sarah Proehl,Carrie Heusner,Charles A McWherter,Daria B Crittenden,\",\"doi\":\"10.14309/ajg.0000000000003603\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"OBJECTIVES\\r\\nEvaluate interim data from the ongoing, open-label, long-term efficacy and safety ASSURE study of seladelpar, a selective peroxisome proliferator-activated receptor δ agonist, in primary biliary cholangitis (PBC).\\r\\n\\r\\nMETHODS\\r\\nPatients rolling over from the phase 3, randomized, placebo-controlled, 12-month RESPONSE study or with previous participation in earlier legacy seladelpar studies were enrolled. Interim evaluations included composite biochemical response (alkaline phosphatase [ALP] <1.67×upper limit of normal [ULN], total bilirubin ≤ULN, and ALP decrease ≥15%), pruritus numerical rating scale (NRS) change among patients with a baseline score ≥4, and safety.\\r\\n\\r\\nRESULTS\\r\\nAt interim cutoff, 337 patients were enrolled and received ≥1 seladelpar 10-mg dose; 54 placebo-treated and 104 seladelpar-treated from RESPONSE and 179 from legacy studies. The composite response rate at RESPONSE completion was 62% (79/128) with seladelpar and 20% (13/65) with placebo. After 12 months in ASSURE, response rates were 72% (21/29) in patients continuing seladelpar and 94% (15/16) in crossover seladelpar patients. In legacy trial patients, response rates were 73% (120/164) and 70% (69/99) after 12 and 24 months of treatment in ASSURE, respectively. The NRS decrease at RESPONSE completion in seladelpar-treated patients with baseline NRS ≥4 (-3.4) was maintained after 6 additional months of treatment (-3.8); changes were similar in crossover seladelpar (-3.8) and legacy patients (-3.5) after 6 months of treatment in ASSURE. No seladelpar-related serious adverse events were reported.\\r\\n\\r\\nCONCLUSIONS\\r\\nSeladelpar demonstrated durable improvements in cholestatic biomarkers and pruritus in patients with PBC with up to 2 years of treatment and remained overall safe with long-term use.\",\"PeriodicalId\":520099,\"journal\":{\"name\":\"The American Journal of Gastroenterology\",\"volume\":\"6 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-06-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The American Journal of Gastroenterology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.14309/ajg.0000000000003603\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The American Journal of Gastroenterology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14309/ajg.0000000000003603","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Long-term Efficacy and Safety of Selective PPARδ Agonist Seladelpar in Primary Biliary Cholangitis: ASSURE Interim Study Results.
OBJECTIVES
Evaluate interim data from the ongoing, open-label, long-term efficacy and safety ASSURE study of seladelpar, a selective peroxisome proliferator-activated receptor δ agonist, in primary biliary cholangitis (PBC).
METHODS
Patients rolling over from the phase 3, randomized, placebo-controlled, 12-month RESPONSE study or with previous participation in earlier legacy seladelpar studies were enrolled. Interim evaluations included composite biochemical response (alkaline phosphatase [ALP] <1.67×upper limit of normal [ULN], total bilirubin ≤ULN, and ALP decrease ≥15%), pruritus numerical rating scale (NRS) change among patients with a baseline score ≥4, and safety.
RESULTS
At interim cutoff, 337 patients were enrolled and received ≥1 seladelpar 10-mg dose; 54 placebo-treated and 104 seladelpar-treated from RESPONSE and 179 from legacy studies. The composite response rate at RESPONSE completion was 62% (79/128) with seladelpar and 20% (13/65) with placebo. After 12 months in ASSURE, response rates were 72% (21/29) in patients continuing seladelpar and 94% (15/16) in crossover seladelpar patients. In legacy trial patients, response rates were 73% (120/164) and 70% (69/99) after 12 and 24 months of treatment in ASSURE, respectively. The NRS decrease at RESPONSE completion in seladelpar-treated patients with baseline NRS ≥4 (-3.4) was maintained after 6 additional months of treatment (-3.8); changes were similar in crossover seladelpar (-3.8) and legacy patients (-3.5) after 6 months of treatment in ASSURE. No seladelpar-related serious adverse events were reported.
CONCLUSIONS
Seladelpar demonstrated durable improvements in cholestatic biomarkers and pruritus in patients with PBC with up to 2 years of treatment and remained overall safe with long-term use.