The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC.

Michael Trauner; Aliya Gulamhusein; Bilal Hameed; Stephen Caldwell; Mitchell L Shiffman; Charles Landis; Bertus Eksteen; Kosh Agarwal; Andrew Muir; Simon Rushbrook; Xiaomin Lu; Jun Xu; Jen-Chieh Chuang; Andrew N Billin; Chuhan Chung; Georgia Li; G Mani Subramanian; Robert P Myers; Christopher L Bowlus; Kris V Kowdley

The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC.

Michael Trauner
, Aliya Gulamhusein
, Bilal Hameed
, Stephen Caldwell
, Mitchell L Shiffman
, Charles Landis
, Bertus Eksteen
, Kosh Agarwal
, Andrew Muir
, Simon Rushbrook
, Xiaomin Lu
, Jun Xu
, Jen-Chieh Chuang
, Andrew N Billin
, Chuhan Chung
, Georgia Li
, G Mani Subramanian
, Robert P Myers
, Christopher L Bowlus
, Kris V Kowdley

Research output: Contribution to journal › Article

Abstract

Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a Phase 2 double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor (FXR) agonist in non-cirrhotic patients with large duct PSC. Patients were randomized to receive cilofexor 100 mg (n=22), 30 mg (n=20), or placebo (n=10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) >1.67xULN and total bilirubin ≤2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58% male, 60% with IBD, 46% on UDCA). Baseline median serum ALP and bilirubin were 348 U/L (IQR 288-439) and 0.7 mg/dL (0.5-1.0), respectively. Dose-dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction -21%; p=0.029 vs placebo), GGT (-30%;p

Original language	American English
Journal	Articles, Abstracts, and Reports
State	Published - Jan 19 2019

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Trauner, M., Gulamhusein, A., Hameed, B., Caldwell, S., Shiffman, M. L., Landis, C., Eksteen, B., Agarwal, K., Muir, A., Rushbrook, S., Lu, X., Xu, J., Chuang, J.-C., Billin, A. N., Chung, C., Li, G., Subramanian, G. M., Myers, R. P., Bowlus, C. L., & Kowdley, K. V. (2019). The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC. Articles, Abstracts, and Reports. http://digitalcommons.providence.org/publications/1077

@article{7663099cb5da4b7caff40e3882236c3d,

title = "The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC.",

abstract = "Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a Phase 2 double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor (FXR) agonist in non-cirrhotic patients with large duct PSC. Patients were randomized to receive cilofexor 100 mg (n=22), 30 mg (n=20), or placebo (n=10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) >1.67xULN and total bilirubin ≤2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58\% male, 60\% with IBD, 46\% on UDCA). Baseline median serum ALP and bilirubin were 348 U/L (IQR 288-439) and 0.7 mg/dL (0.5-1.0), respectively. Dose-dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction -21\%; p=0.029 vs placebo), GGT (-30\%;p",

author = "Michael Trauner and Aliya Gulamhusein and Bilal Hameed and Stephen Caldwell and Shiffman, \{Mitchell L\} and Charles Landis and Bertus Eksteen and Kosh Agarwal and Andrew Muir and Simon Rushbrook and Xiaomin Lu and Jun Xu and Jen-Chieh Chuang and Billin, \{Andrew N\} and Chuhan Chung and Georgia Li and Subramanian, \{G Mani\} and Myers, \{Robert P\} and Bowlus, \{Christopher L\} and Kowdley, \{Kris V\}",

year = "2019",

month = jan,

day = "19",

language = "American English",

journal = "Articles, Abstracts, and Reports",

}

Trauner, M, Gulamhusein, A, Hameed, B, Caldwell, S, Shiffman, ML, Landis, C, Eksteen, B, Agarwal, K, Muir, A, Rushbrook, S, Lu, X, Xu, J, Chuang, J-C, Billin, AN, Chung, C, Li, G, Subramanian, GM, Myers, RP, Bowlus, CL & Kowdley, KV 2019, 'The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC.', Articles, Abstracts, and Reports. <http://digitalcommons.providence.org/publications/1077>

TY - JOUR

T1 - The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC.

AU - Trauner, Michael

AU - Gulamhusein, Aliya

AU - Hameed, Bilal

AU - Caldwell, Stephen

AU - Shiffman, Mitchell L

AU - Landis, Charles

AU - Eksteen, Bertus

AU - Agarwal, Kosh

AU - Muir, Andrew

AU - Rushbrook, Simon

AU - Lu, Xiaomin

AU - Xu, Jun

AU - Chuang, Jen-Chieh

AU - Billin, Andrew N

AU - Chung, Chuhan

AU - Li, Georgia

AU - Subramanian, G Mani

AU - Myers, Robert P

AU - Bowlus, Christopher L

AU - Kowdley, Kris V

PY - 2019/1/19

Y1 - 2019/1/19

N2 - Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a Phase 2 double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor (FXR) agonist in non-cirrhotic patients with large duct PSC. Patients were randomized to receive cilofexor 100 mg (n=22), 30 mg (n=20), or placebo (n=10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) >1.67xULN and total bilirubin ≤2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58% male, 60% with IBD, 46% on UDCA). Baseline median serum ALP and bilirubin were 348 U/L (IQR 288-439) and 0.7 mg/dL (0.5-1.0), respectively. Dose-dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction -21%; p=0.029 vs placebo), GGT (-30%;p

AB - Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a Phase 2 double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor (FXR) agonist in non-cirrhotic patients with large duct PSC. Patients were randomized to receive cilofexor 100 mg (n=22), 30 mg (n=20), or placebo (n=10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) >1.67xULN and total bilirubin ≤2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58% male, 60% with IBD, 46% on UDCA). Baseline median serum ALP and bilirubin were 348 U/L (IQR 288-439) and 0.7 mg/dL (0.5-1.0), respectively. Dose-dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction -21%; p=0.029 vs placebo), GGT (-30%;p

M3 - Article

JO - Articles, Abstracts, and Reports

JF - Articles, Abstracts, and Reports

ER -

The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC.

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