Z Gastroenterol 2020; 58(08): e114-e115
DOI: 10.1055/s-0040-1716044
BEST Abstracts: Präsentationen
BEST Abstracts: Hepatologie - klinisch II Mittwoch, 16. September 2020, 16:00 - 17:10

Obeticholic acid treatment in patients with non-alcoholic steatohepatitis: a secondary analysis of the REGENERATE study across fibrosis stages

A Geier
1   Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Deutschland
,
AJ Sanyal
2   Virginia Commonwealth University, Richmond, Vereinigte Staaten von Amerika
,
V Ratziu
3   Sorbonne Université, Hôpital Pitié - Salpêtrière, Paris, Frankreich
,
R Loomba
4   University of California, San Diego, San Diego, Vereinigte Staaten von Amerika
,
M Rinella
5   Feinberg School of Medicine, Northwestern University, Chicago, Vereinigte Staaten von Amerika
,
QM Anstee
6   Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, Vereinigtes Königreich
,
Z Goodman
7   Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Vereinigte Staaten von Amerika
,
P Bedossa
8   Service d’Anatomie Pathologique, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Paris, Frankreich
,
M Khalili
9   University of California, San Francisco, San Francisco, Vereinigte Staaten von Amerika
,
J Boursier
10   Angers University Hospital, Angers, Frankreich
,
L Stinton
11   University of Calgary, Calgary, Kanada
,
G Marchesini
12   University of Bologna, Bologna, Italien
,
M Allison
13   Addenbrookes Hospital, Cambridge, Vereinigtes Königreich
,
J George
14   Westmead Hospital, Sydney, Australien
,
P Arkkila
15   Meilahti Tower Hospital, Meilahti Tower Hospital, Helsinki, Finnland
,
L Zaru
16   Intercept Pharmaceuticals, Inc., San Diego, Vereinigte Staaten von Amerika
,
L Mac Conell
16   Intercept Pharmaceuticals, Inc., San Diego, Vereinigte Staaten von Amerika
,
R Shringarpure
16   Intercept Pharmaceuticals, Inc., San Diego, Vereinigte Staaten von Amerika
,
ZY Younossi
7   Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, Vereinigte Staaten von Amerika
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    Background Previous studies have shown that diabetes, hypertension and elevated transaminases are drivers of fibrosis progression in patients with non-alcoholic steatohepatitis (NASH). F1 patients with comorbidities are at a higher risk of rapid progression to advanced fibrosis. In REGENERATE, an ongoing, double-blind, placebo (PBO)-controlled outcomes study, results of the 18-month interim analysis based on surrogate endpoints showed that obeticholic acid (OCA) improved liver fibrosis in F2/F3 patients.1 The objective of this secondary analysis was to assess the effect of OCA in patients with fibrosis due to NASH including those with early fibrosis but at risk of disease progression.

    Methods The full efficacy (FE) population included patients with NASH and fibrosis stages F2/F3, and F1 with at least one risk factor (BMI≥30 kg/m2, type 2 diabetes, ALT >1.5x ULN), who were randomized 1:1:1 to placebo (PBO), OCA 10 mg, or OCA 25 mg QD. Primary endpoints were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis per liver biopsy. The safety population included all randomized patients who received at least one dose of study treatment (F1-3, N = 1968).

    Results The FE population included 1218 patients (PBO [n=407], OCA 10 mg [n=407] or OCA 25 mg [n=404]), comprised of approximately 24 % F1 and 76 % F2/F3 patients. Baseline characteristics were well-balanced across groups. Overall, in the FE population nearly twice as many patients treated with OCA 25 mg met the primary fibrosis and NASH endpoints compared to PBO (table). In addition, dose-dependent reductions in ALT, AST and GGT were observed. Overall, pruritus was the most common adverse event (AE) (19 % PBO, 28 % OCA 10 mg, 51 % OCA 25 mg) and was predominantly mild to moderate in severity. Serious AEs occurred in 11 % PBO, 11 % OCA 10 mg and 14 % OCA 25 mg patients.

    Conclusion After 18 months of treatment, OCA improved liver fibrosis, steatohepatitis and liver biochemistry in F1-F3 patients, demonstrating consistent efficacy with an overall similar safety profile to that previously reported in the REGENERATE primary efficacy analysis population (F2/F3 intention-to-treat).


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    08. September 2020

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