Hepatology communications · 2026
Seladelpar in patients with primary biliary cholangitis and compensated cirrhosis: Efficacy and safety from RESPONSE and ASSURE studies.
СтатьяРандомизированное исследованиеКлиническое исследование III фазыНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Gordon Stuart C, Villamil Alejandra, Jacobson Ira M, Lawitz Eric J, Younes Ziad, Silveira Marina G, Bowlus Christopher L, Drenth Joost P H, Vierling John M, Morgera Ulrike, Vasura Adam, Dalekos George, Galli Andrea, Rabinovitz Mordechai, Heo Jeong, Nevens Frederik, Levy Cynthia, Zhou Yan, Carroll Susheela, Crittenden Daria B
Аннотация
BACKGROUND: Treatment options are limited for patients with primary biliary cholangitis (PBC) and cirrhosis. Seladelpar, a first-in-class delpar (selective PPAR-δ agonist), had generally similar efficacy and safety among patients with versus without compensated cirrhosis in the phase 3 RESPONSE study. Here we provide additional data on seladelpar in patients with compensated cirrhosis from the phase 3 program.
METHODS: In RESPONSE, patients with PBC and an inadequate response or intolerance to UDCA were randomized 2:1 to seladelpar 10 mg or placebo for 1 year. Upon completion, patients rolled over into the open-label (seladelpar 10 mg) phase 3 ASSURE study, which also enrolled patients from earlier seladelpar legacy PBC studies. Here, we assessed the composite endpoint [alkaline phosphatase (ALP) <1.67×upper limit of normal (ULN), ALP decrease ≥15%, and total bilirubin ≤ULN], other laboratory changes, and safety in all patients with cirrhosis from RESPONSE and an interim analysis of the ongoing ASSURE study through January 2024.
RESULTS: Twenty-seven patients with compensated cirrhosis enrolled in RESPONSE (18 seladelpar, 9 placebo). At month 12, 38.9% and 22.2% of patients in the seladelpar and placebo groups, respectively, met the composite endpoint; mean percent change from baseline in ALP was -37.1% and -10.1%, respectively. Upon rollover to ASSURE (13 seladelpar, 6 placebo), ALP declines were maintained for up to 18 months. An additional 35 patients with compensated cirrhosis in ASSURE from legacy studies had similar reductions in ALP with up to 2 years of treatment. Bilirubin remained overall stable. No treatment-related serious adverse events occurred. Variceal bleeding and/or ascites developed in 3 patients after ≥9 months.
CONCLUSIONS: Seladelpar decreased markers of cholestasis and was overall safe and well-tolerated in patients with PBC and compensated cirrhosis.
METHODS: In RESPONSE, patients with PBC and an inadequate response or intolerance to UDCA were randomized 2:1 to seladelpar 10 mg or placebo for 1 year. Upon completion, patients rolled over into the open-label (seladelpar 10 mg) phase 3 ASSURE study, which also enrolled patients from earlier seladelpar legacy PBC studies. Here, we assessed the composite endpoint [alkaline phosphatase (ALP) <1.67×upper limit of normal (ULN), ALP decrease ≥15%, and total bilirubin ≤ULN], other laboratory changes, and safety in all patients with cirrhosis from RESPONSE and an interim analysis of the ongoing ASSURE study through January 2024.
RESULTS: Twenty-seven patients with compensated cirrhosis enrolled in RESPONSE (18 seladelpar, 9 placebo). At month 12, 38.9% and 22.2% of patients in the seladelpar and placebo groups, respectively, met the composite endpoint; mean percent change from baseline in ALP was -37.1% and -10.1%, respectively. Upon rollover to ASSURE (13 seladelpar, 6 placebo), ALP declines were maintained for up to 18 months. An additional 35 patients with compensated cirrhosis in ASSURE from legacy studies had similar reductions in ALP with up to 2 years of treatment. Bilirubin remained overall stable. No treatment-related serious adverse events occurred. Variceal bleeding and/or ascites developed in 3 patients after ≥9 months.
CONCLUSIONS: Seladelpar decreased markers of cholestasis and was overall safe and well-tolerated in patients with PBC and compensated cirrhosis.