Pharmaceutical firms around the world are striving to become the world’s first to release treatment for nonalcoholic steatohepatitis (NASH), or nonalcoholic fatty liver.
Despite various clinical trials on new drug candidates, drugmakers found it hard to discover a candidate that shows a therapeutic effect strong enough for approval.
Most recently, Gilead said it failed to reach a primary endpoint in a phase-3 trial on selonsertib.
Intercept Pharmaceutical’s latest announcement that it achieved a primary endpoint in a phase-3 trial on investigational drug obeticholic acid (OCA) is drawing attention.
However, it remains to be seen how Intercept will address the issue of side effects raised during the trial such as pruritus and an increase in LDL cholesterol.
On Tuesday, Intercept said REGENERATE, a phase-3 trial on OCA in patients with liver fibrosis caused by NASH, yielded positive results.
REGENERATE is a global, phase-3, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of OCA in patients with liver fibrosis caused by NASH. It is taking place on more than 2,000 patients with the disease in stage 2 or 3 registered at 339 institutions around the world.
The company said 23.1 percent of patients treated with OCA 25mg had fibrosis improvement with no worsening of NASH, compared to 11.9 percent in the placebo group, meaning that the experimental drug met its primary endpoint.
In the additional overall efficacy analysis including those on patients with first-stage liver fibrosis, the proportion of patients with fibrosis improvement without worsening of NASH was 10.6 percent in the placebo group, 15.7 percent in the OCA 10mg group, and 21 percent in the OCA 25mg group.
However, the differences in the proportions of patients who showed resolution of NASH without worsening fibrosis among the three groups were not statistically meaningful – 8 percent in the placebo group, 11.2 percent in the OCA 10mg group, and 11.7 percent in the OCA 25mg group.
Even though the OCA 25mg group proved the drug candidate’s efficacy in fibrosis improvement, the trial could not confirm the safety due to the reports of dose-related side effect of pruritus.
The most common adverse event reported was pruritus – 19 percent in the placebo, 28 percent in OCA 10 mg and 51 percent in OCA 25 mg.
The OCA treatment also showed an association with an increase in LDL cholesterol. The LCL cholesterol went up to 22.6 mg/dL at the fourth week and slid down to 4 mg/dL above the baseline at the 18th month.
As for hepatobiliary events, 3 percent of patients with OCA 25 mg experienced gallstones or cholecystitis, compared to less than 1 percent of patients on placebo, and 1 percent of those on OCA 10 mg.
Intercept is also conducting a phase-3 trial REVERSE on OCA’s efficacy and safety in patients with liver cirrhosis caused by NASH.
Based on the results of the GENERATE study, the company plans to apply for approval of OCA in the U.S. and Europe in the second half of the year.
The company said it would present the study outcome at the European Association for the Study of the Liver 2019 International Liver Congress in Vienna, Austria, from April 10-14.
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