Intercept reports additional positive data for Ocaliva in late-stage NASH trial

Intercept Pharmaceuticals presented additional supportive efficacy analyses Thursday at the European Association for the Study of the Liver (EASL) annual meeting from the Phase III REGENERATE trial. Earlier this year, Intercept said the study had achieved the primary endpoint of fibrosis improvement with no worsening of nonalcoholic steatohepatitis (NASH) at the planned 18-month interim analysis. 

Zobair Younossi, chair of the REGENERATE steering committee, remarked "halting or reversing fibrosis is a central therapeutic objective for patients with NASH, so the results from the 18-month interim analysis of REGENERATE are highly meaningful and clinically important." He said the new data suggest Ocaliva "also improves other important measures of liver health, including the key underlying drivers of NASH and biochemical tests that clinicians routinely monitor when managing patients in the real world." 

Neverthless, shares in Intercept fell more than 12 percent on the news. Bloomberg Intelligence analyst Asthika Goonewardene explained that despite the positive study results, investors are worried about how patients will continue treatment because of side effects, stating "first to market in NASH is not that much of a positive if you can't follow through and make the market happen." The analyst added "it's going to be a tough competition for them."

The additional supportive efficacy analyses assessed outcomes in the per protocol population, a subset of the REGENERATE study population of patients with liver fibrosis due to NASH consisting of 668 participants who completed at least 15 months of treatment and underwent biopsy at 18 months or at the end of treatment. Patients had been randomised to once-daily Ocaliva at a low or high dose, or placebo. 

Results from the updated analysis revealed that 13.3 percent of patients in the high-dose Ocaliva arm achieved at least a two-stage improvement in fibrosis, compared with 4.5 percent for placebo. In addition, 38 percent and 13.1 percent of patients in the high-dose group experienced at least a one-stage improvement versus worsening of fibrosis, respectively, while in the placebo arm the respective rates were 23.2 percent and 20.9 percent. 

Meanwhile, 43.6 percent of patients given high-dose Ocaliva had a one-point or better improvement in hepatocellular ballooning, compared with 28.6 percent of placebo-treated patients, while the rates of at least a one-point improvement of lobular inflammation in these two groups were 52.3 percent and 42 percent, respectively. Further, Intercept said there were "rapid and sustained reductions" in certain liver parameters, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), among Ocaliva-treated patients. Specifically, 65.6 percent and 54.7 percent of patients with elevated ALT and AST levels at baseline, respectively, experienced normalisation in the high-dose Ocaliva group, compared with 37.3 percent and 29.3 percent for placebo.

Ocaliva was previously awarded a breakthrough therapy designation by the FDA for use in patients with NASH with liver fibrosis. In 2016, the farnesoid X receptor agonist also received accelerated approval in the US for primary biliary cholangitis. 

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