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news.Intercept Pharmaceuticals has announced the results of a 72-week Phase 2 dose ranging trial of obeticholic acid (OCA), Intercept's lead FXR agonist, in adult patients with nonalcoholic steatohepatitis (NASH) in Japan.
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This trial is the first to evaluate the safety and efficacy of OCA in Japanese NASH patients. The primary efficacy analysis was conducted on an intention to treat (ITT) basis, testing the dose dependent effects of once daily OCA (10mg, 20mg and 40mg) versus placebo on the primary endpoint of a two point improvement in the NAFLD Activity Score (NAS) with no worsening of fibrosis.
The ITT analysis included all randomized patients who received treatment (50 per group), and patients who discontinued or did not have a repeat biopsy were treated as non-responders.
A pre-specified completer analysis was conducted on the patients who had biopsies at both baseline and 72 weeks (45, 44, 44 and 37 patients in the placebo, 10mg, 20mg and 40mg OCA groups, respectively).
The ITT results in the table below show a dose dependent increase in the percentage of OCA treated patients compared to placebo who achieved the primary endpoint (p=0.053, not significant). The 40mg OCA dose group achieved statistical significance on the primary endpoint compared to placebo (p=0.0496).
Dose-dependent trends not reaching statistical significance were also observed for several other pre-specified histologic endpoints, including the proportion of patients with steatosis and inflammation improvement, ballooning resolution and NASH resolution. No difference was seen in fibrosis improvement in the OCA groups compared to placebo.
In the completer analysis, similar dose dependent effects were observed, with 51% of patients in the 40mg dose group compared to 22% in the placebo group meeting the primary endpoint (p=0.0061).
With the exception of dose dependent pruritus, OCA appeared to be generally safe and well tolerated. The number of pruritus associated discontinuations were 0, 0, 2 and 5 patients in the placebo, 10mg, 20mg and 40mg OCA groups, respectively.
Changes in lipid parameters, including LDL-C, HDL-C and triglycerides, appeared to be consistent with previously reported lipid changes in Western NASH patients. No other meaningful differences in the rate of adverse events between the OCA and placebo groups were noted.
Intercept CEO and president Mark Pruzanski said: "This study provides the first data on safety, efficacy and dose effects for OCA in Japanese NASH patients and we look forward to continuing to work with our partner Sumitomo Dainippon Pharma to understand the results further.
"There were distinct differences in baseline characteristics in this study population when compared to the Western patients in the previously conducted FLINT trial. We are currently actively enrolling our Phase 3 REGENERATE trial, which was designed based on the robust FLINT results to evaluate OCA’s safety and efficacy in a similar Western patient population."