@article{discovery10173725,
           month = {April},
          number = {2},
           title = {Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study},
            year = {2023},
       publisher = {Ovid Technologies (Wolters Kluwer Health)},
         journal = {Hepatology},
          volume = {78},
            note = {This work is licensed under a Creative Commons Attribution 4.0 International License. The images
or other third-party material in this article are included in the Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
license, visit http://creativecommons.org/licenses/by/4.0/},
           pages = {397--415},
             url = {https://doi.org/10.1097/hep.0000000000000395},
        abstract = {Background and Aims:


            ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-{\ensuremath{\delta}} (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).


          
          
            Approach and Results:


            Patients 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{$\times$}upper limit of normal (ULN), {$\ge$}15\% ALP decrease from baseline, and total bilirubin {$\leq$} 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 {$\ge$}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.


          
          
            Conclusions:


            Patients 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.},
          author = {Hirschfield, Gideon M and Shiffman, Mitchell L and Gulamhusein, Aliya and Kowdley, Kris V and Vierling, John M and Levy, Cynthia and Kremer, Andreas E and Zigmond, Ehud and Andreone, Pietro and Gordon, Stuart C and Bowlus, Christopher L and Lawitz, Eric J and Aspinall, Richard J and Pratt, Daniel S and Raikhelson, Karina and Gonzalez-Huezo, Maria S and Heneghan, Michael A and Jeong, Sook-Hyang and Ladr{\'o}n de Guevara, Alma L and Mayo, Marlyn J and Dalekos, George N and Drenth, Joost PH and Janczewska, Ewa and Leggett, Barbara A and Nevens, Frederik and Vargas, Victor and Zuckerman, Eli and Corpechot, Christophe and Fassio, Eduardo and Hinrichsen, Holger and Invernizzi, Pietro and Trivedi, Palak J and Forman, Lisa and Jones, David EJ and Ryder, Stephen D and Swain, Mark G and Steinberg, Alexandra and Boudes, Pol F and Choi, Yun-Jung and McWherter, Charles A}
}