Obeticholic acid: A first for NASH?
Patients with non-alcoholic steatohepatitis (NASH) may benefit from treatment with a 25 mg/day dose of obeticholic acid, according to the interim analysis of the phase III REGENERATE* study presented at the International Liver Congress™ (ILC 2019).
“These first results from the REGENERATE study give us hope that a new targeted approach to NASH treatment may soon become available and potentially reverse some of the liver damage associated with this important liver disease,” said Professor Zobair Younossi, chairman of the Department of Medicine, Inova Fairfax Medical Campus in Falls Church, Virginia, US, who presented the findings at the congress.
A total of 931 patients with NASH and fibrosis stage F2–F3 were randomized to receive obeticholic acid at doses of either 10 or 25 mg/day (n=312 and 308, respectively) or placebo (n=311). There was a slightly higher proportion of patients with fibrosis stage F3 than F2 (56 percent vs 44 percent).
The analysis, conducted 18 months into the trial, showed that a greater proportion of patients treated with obeticholic acid experienced ≥1 stage improvement in fibrosis without deterioration of NASH than those treated with placebo (23.1 percent [25 mg/day] and 17.6 percent [10 mg/day] vs 11.9 percent [placebo]; p=0.0002 and p=0.0446, respectively, vs placebo). [ILC 2019, abstract GS-06]
However, the incidence of NASH resolution coupled with no worsening of fibrosis was comparable between patients on placebo (8.0 percent) and obeticholic acid (11.2 and 11.7 percent for 10 and 25 mg/day, respectively; p=0.1814 and p=0.1268, respectively, vs placebo).
More patients treated with obeticholic acid 25 mg/day than placebo experienced improvements in hepatocellular ballooning (35.1 percent vs 23.2 percent; p=0.0011) and lobular inflammation (44.2 percent vs 35.7 percent; p=0.0322, respectively), while improvements in hepatocellular ballooning and lobular inflammation were comparable between patients on obeticholic acid 10 mg/day and placebo (27.2 and 39.1 percent, respectively; p=0.2423 and p=0.3380, respectively, vs placebo).
The most frequent adverse event (AE) was pruritus, occurring in 51, 28, and 19 percent of patients on obeticholic acid 25 mg/day, 10 mg/day, and placebo, respectively, and leading to treatment discontinuation in 9 percent of patients on obeticholic acid 25 mg/day and <1 percent of patients on placebo or obeticholic acid 10 mg/day. Serious AEs occurred at a comparable rate between patients on obeticholic acid 10 and 25 mg/day and placebo (11, 14, and 11 percent, respectively), as did serious cardiovascular AEs (1, 2, and 2 percent, respectively). Cholelithiasis or cholecystitis occurred in 3 percent of patients on obeticholic acid 25 mg/day and 1 percent each among patients on placebo and obeticholic acid 10 mg/day.
None of the three deaths that occurred up to the point of analysis were deemed related to treatment.
“There is an urgent need for effective treatment regimens for NASH, a common liver disease which can lead to cirrhosis, liver failure, and need for transplant,” said Younossi.
“These data are very exciting as they demonstrate for the first time in a phase III trial that medical therapy, in this case obeticholic acid, is able to improve liver fibrosis compared to placebo – a key treatment goal in NASH,” added Professor Philip Newsome, vice-secretary of the European Association for the Study of the Liver (EASL), who was not affiliated with the trial.