1. Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study.
- Author
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Hirschfield, Gideon M, Shiffman, Mitchell L, Gulamhusein, Aliya, Kowdley, Kris V, Vierling, John M, Levy, Cynthia, Kremer, Andreas E, Zigmond, Ehud, Andreone, Pietro, Gordon, Stuart C, Bowlus, Christopher L, Lawitz, Eric J, Aspinall, Richard J, Pratt, Daniel S, Raikhelson, Karina, Gonzalez-Huezo, Maria S, Heneghan, Michael A, Jeong, Sook-Hyang, Ladrón de Guevara, Alma L, Mayo, Marlyn J, Dalekos, George N, Drenth, Joost PH, Janczewska, Ewa, Leggett, Barbara A, Nevens, Frederik, Vargas, Victor, Zuckerman, Eli, Corpechot, Christophe, Fassio, Eduardo, Hinrichsen, Holger, Invernizzi, Pietro, Trivedi, Palak J, Forman, Lisa, Jones, David EJ, Ryder, Stephen D, Swain, Mark G, Steinberg, Alexandra, Boudes, Pol F, Choi, Yun-Jung, McWherter, Charles A, and ENHANCE Study Group*
- Subjects
ENHANCE Study Group* ,Humans ,Liver Cirrhosis ,Biliary ,Pruritus ,Acetates ,Ursodeoxycholic Acid ,Alkaline Phosphatase ,Cholagogues and Choleretics ,Digestive Diseases ,Liver Disease ,Rare Diseases ,Clinical Trials and Supportive Activities ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Immunology ,Gastroenterology & Hepatology - Abstract
Background and aimsENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).Approach and resultsPatients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events.ConclusionsPatients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.
- Published
- 2023