Obeticholic acid (OCA) improves experimental non-invasive markers of NASH and advanced fibrosis: results of a secondary analysis from the month-18 interim analysis of the REGENERATE study

Background The REGENERATE month-18 interim analysis showed that treatment with OCA improved liver fibrosis in patients with NASH as well as established non-invasive assessments of fibrosis and NASH. New biomarker indices are being developed to improve ability to predict NASH grade and fibrosis stage. FibroMeter (FM) is designed to predict presence of significant fibrosis (F ≥ 2). FM combines age, gender, alpha 2 macroglobilin (A2M), INR, platelets, urea and GGT, while FM VCTE uses the same biomarkers except urea and includes liver stiffness (LS) by vibration-controlled transient elastography (VCTE). The FAST score, designed to identify patients with NASH and NAFLD Activity Score (NAS) ≥ 4 and F ≥ 2, combines LS by VCTE with Controlled Attenuation Parameter (CAP) score and AST.

Methods NASH patients with fibrosis stages 2 and 3 were randomized (1:1:1) to placebo (N=311), OCA 10 mg (n=312) or OCA 25 mg (N=308) QD. In a subset of patients with available values, changes in FM (N=604), FM VCTE (N=604), and FAST (N=391) were analyzed using mixed-effect repeated measures model with treatment, baseline, visit, visit by treatment interaction and stratification factors to be included in the model. LS mean and p-values are based on mixed-effect repeated measure model.

Results At baseline, there was no significant difference in scores across treatment groups. Patients with stage 3 fibrosis at baseline had higher scores than those with stage 2 fibrosis, consistent with prior publications (data not shown).

OCA-treated patients experienced improvements in FM, FM VCTE and FAST as of the first assessed timepoint (month 6) which were sustained through month 18. While this therapeutic response was observed in both OCA dose groups, no improvement was observed in the placebo group.

Conclusion OCA treatment resulted in early and sustained improvements in experimental non-invasive assessments of fibrosis NASH, consistent with previously reported histologic improvements. Specifically, improvements in FM and FM VCTE are consistent with OCA’s anti-fibrotic effect, while improvements in FAST are consistent with amelioration of key histologic features of NASH, including both inflammation and fibrosis.

Publication History

Article published online:
08 September 2020