eprintid: 10173725
rev_number: 8
eprint_status: archive
userid: 699
dir: disk0/10/17/37/25
datestamp: 2023-07-21 13:11:34
lastmod: 2023-07-21 13:11:34
status_changed: 2023-07-21 13:11:34
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Hirschfield, Gideon M
creators_name: Shiffman, Mitchell L
creators_name: Gulamhusein, Aliya
creators_name: Kowdley, Kris V
creators_name: Vierling, John M
creators_name: Levy, Cynthia
creators_name: Kremer, Andreas E
creators_name: Zigmond, Ehud
creators_name: Andreone, Pietro
creators_name: Gordon, Stuart C
creators_name: Bowlus, Christopher L
creators_name: Lawitz, Eric J
creators_name: Aspinall, Richard J
creators_name: Pratt, Daniel S
creators_name: Raikhelson, Karina
creators_name: Gonzalez-Huezo, Maria S
creators_name: Heneghan, Michael A
creators_name: Jeong, Sook-Hyang
creators_name: Ladrón de Guevara, Alma L
creators_name: Mayo, Marlyn J
creators_name: Dalekos, George N
creators_name: Drenth, Joost PH
creators_name: Janczewska, Ewa
creators_name: Leggett, Barbara A
creators_name: Nevens, Frederik
creators_name: Vargas, Victor
creators_name: Zuckerman, Eli
creators_name: Corpechot, Christophe
creators_name: Fassio, Eduardo
creators_name: Hinrichsen, Holger
creators_name: Invernizzi, Pietro
creators_name: Trivedi, Palak J
creators_name: Forman, Lisa
creators_name: Jones, David EJ
creators_name: Ryder, Stephen D
creators_name: Swain, Mark G
creators_name: Steinberg, Alexandra
creators_name: Boudes, Pol F
creators_name: Choi, Yun-Jung
creators_name: McWherter, Charles A
title: Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
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abstract: Background and Aims:
ENHANCE 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 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×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.
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.
date: 2023-04-06
date_type: published
publisher: Ovid Technologies (Wolters Kluwer Health)
official_url: https://doi.org/10.1097/hep.0000000000000395
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2038729
doi: 10.1097/hep.0000000000000395
lyricists_name: Thorburn, Douglas
lyricists_id: DTHOR21
actors_name: Thorburn, Douglas
actors_name: Flynn, Bernadette
actors_id: DTHOR21
actors_id: BFFLY94
actors_role: owner
actors_role: impersonator
full_text_status: public
publication: Hepatology
volume: 78
number: 2
pagerange: 397-415
citation: Hirschfield, Gideon M; Shiffman, Mitchell L; Gulamhusein, Aliya; Kowdley, Kris V; Vierling, John M; Levy, Cynthia; Kremer, Andreas E; ... McWherter, Charles A; + view all <#> 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; - view fewer <#> (2023) Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study. Hepatology , 78 (2) pp. 397-415. 10.1097/hep.0000000000000395 <https://doi.org/10.1097/hep.0000000000000395>. Green open access
document_url: https://discovery.ucl.ac.uk/id/eprint/10173725/1/hep-78-397.pdf