Obeticholic Acid Efficacy in Patients With NASH Monitored Using Noninvasive Tests: Post Hoc Analysis of REGENERATE Trial

Question Liver biopsies are not practical for monitoring patients with NASH. Noninvasive tests (NITs) are effective tools for diagnosis and evaluation of these patients. Obeticholic acid (OCA) is an antifibrotic in clinical development for the treatment of advanced fibrosis due to NASH. This post hoc analysis evaluated NIT-based OCA efficacy in patients from REGENERATE stratified by fibrosis stage using NITs.

Methods The phase 3, multicenter, randomized, double-blind REGENERATE trial is ongoing worldwide. This post hoc analysis evaluated the NIT-based efficacy of OCA 25 mg vs placebo (PBO) in patients from the intent-to-treat (ITT) population of the REGENERATE 18-month interim analysis with Fibrosis-4 (FIB-4) and transient elastography (TE) data available at baseline. Using published cutoffs, FIB-4 and TE were applied sequentially to categorize patients. Indeterminate patients scored indeterminate on FIB-4 (≥1.30‒ < 2.67) and TE (≥7.9‒ < 9.6 kPa); advanced fibrosis patients scored advanced on FIB-4 (≥2.67) or indeterminate on FIB-4 (≥1.30‒ < 2.67) and as advanced fibrosis on TE (≥9.6 kPa) at baseline. Alanine aminotransferase (ALT) levels, FIB-4, and TE scores were evaluated at baseline and at months 6, 12, and 18 in patients treated with OCA 25 mg or PBO; patients with indeterminant status for advanced fibrosis or advanced fibrosis were pooled.

Results Identified were 543 evaluable NASH patients (OCA 25 mg, n = 266; PBO, n = 277). In the OCA 25 mg and PBO groups, respectively, similar percentages of patients had indeterminate status for advanced fibrosis (6 % and 5 %) or advanced fibrosis (39 % and 37 %). In the pooled subgroups (indeterminate status + advanced fibrosis), OCA 25 mg treatment reduced ALT below the upper limit of normal for REGENERATE (55 U/L) by month 6 and through month 18 (Figure). Changes from baseline to month 18 in mean ALT and median TE scores in the pooled subgroups of patients were numerically greater for OCA 25 mg vs PBO, respectively (ALT: ‒46.1 U/L vs ‒29.3 U/L; TE: ‒3.4 vs ‒0.55 kPa). In the pooled subgroups at month 18, OCA 25 mg reduced mean ALT scores and median TE scores by 50.1 % and 25.6 %; reductions for PBO were 30.2 % and 4.2 %, respectively.

Conclusions Patients with indeterminate status for advanced fibrosis or advanced fibrosis stratified by baseline NITs in REGENERATE showed improvements in NIT measures with OCA 25 mg vs PBO at month 18. These data support the use of routinely available NITs for monitoring OCA treatment response.

Publication History

Article published online:
04 January 2021