Conatus Pharmaceuticals announced Thursday that a Phase II study of emricasan in patients with nonalcoholic fatty liver disease (NAFLD), including a subset of patients with nonalcoholic steatohepatitis (NASH), met its primary endpoint. Top-line results demonstrated that the orally active pan-caspase protease inhibitor showed a significant reduction in alanine aminotransferase (ALT) versus placebo. Shares in the drugmaker surged more than 50 percent on the news.
In the study, 38 patients with NAFLD were randomised to treatment with emricasan or placebo. After 28 days of treatment, patients in the emricasan arm displayed a 39 percent reduction in ALT levels, compared to 14 percent in the placebo arm. Conatus noted that the reductions were in line with those observed in previous trials.
According to the company, emricasan also significantly reduced elevated baseline levels of the three key serum biomarkers of caspase-cleaved cytokeratin 18 (cCK18), full length cytokeratin 18 and caspases 3 and 7 at day 28. Specifically, cCK18 levels were about 30 percent lower in the emricasan arm, compared to an increase of 4 percent in placebo-treated patients. Conatus noted that the reduction in serum cCK18 levels demonstrated that emricasan can effectively reduce inflammation and elevated levels of apoptosis in NAFLD/NASH patients.
In the study, the therapy was well tolerated, with no dose-limiting toxicities and no drug-related serious adverse events observed in the study. The drug was also not found to adversely affect lipid levels or insulin sensitivity. Conatus indicated that detail study results will be presented next month at The International Liver Congress, the annual meeting of the European Association for the Study of the Liver (EASL).
"With these results...we have confirmed that the optimal dose of emricasan is consistent across different aetiologies," Conatus CEO Steven J. Mento said, adding "and strengthened our belief that inhibiting excessive apoptosis and inflammation will be therapeutic in patients whose liver damage is associated with NASH." David T. Hagerty, the company's executive vice President of clinical development, remarked "we are prepared for planned discussions with regulatory authorities to seek guidance on the appropriate use and analysis of these endpoints in registrational trials including patients with NASH cirrhosis."
Other companies developing therapies for NASH include Gilead Sciences, Intercept Pharmaceuticals and Genfit. For related analysis, read ViewPoints: Breadth of NASH pipeline coming into focus and Physician Views Poll Results – Defining a suitable NASH therapy. For more information on the NASH market, see Nonalcoholic Steatohepatitis: KOL Insight.
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