Interim data from emricasan phase III trial for NASH cirrhosis and portal hypertension
There was no significant difference in severe portal hypertension for patients with non-alcoholic steatohepatitis (NASH) cirrhosis treated with emricasan from Conatus/Novartis versus placebo, according data presented at the European Association for the Study of the Liver (EASL) annual meeting.
No significant change in hepatic venous pressure gradient (HVPG), a key driver of cirrhosis, was observed at week 24, with either a 5-mg, 25-mg, or 50-mg dose of emricasan versus placebo, reported Guadalupe Garcia-Tsao, MD, of Yale University in New Haven, Connecticut, in a late-breaking abstract. While the primary endpoint was not met at the 24-week mark, the trial was a 48-week trial.
A year ago, emricasan, an oral pan-caspase inhibitor, failed to meet its primary endpoint in a phase IIb trial among liver transplant patients with hepatitis C, where the virus had cleared, but who still had fibrosis or cirrhosis.
Researchers performed the multi-center randomized trial at 59 sites in the U.S. and the EU. There were 263 patients with NASH cirrhosis and a baseline HVPG greater than 12 mmHg. They were a mean age of about 61, 57% were women, a large majority were Caucasian; around 85% had type 2 diabetes. About three-quarters of patients had compensated cirrhosis. Patients were randomized 1:1:1:1 to 5-mg, 25-mg, 50-mg of oral emricasan, or a placebo. Overall, there was no significant change in mean HVPG from baseline to week 24 with emricasan versus placebo: 5 mg emricasan: -0.48 mmHg 25 mg: -0.84 mmHg 50 mg: -0.70 mmHg Placebo: -0.18 mmHg . A planned subgroup analysis of patients with compensated cirrhosis also found no significant difference. However, a post-hoc analysis of patients with compensated cirrhosis and HVPG geater than 16 mmHg found what the authors described as a “clinically meaningful reduction” in HVPG with emricasan versus placebo, though not a dose-related effect. They also found that biomarkers cleaved cytokeratin-18 (cCK-18), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and caspase 3/7 were reduced with emricasan compared to placebo.
Treatment-related adverse events were similar for all emricasan groups (81.6% combined emricasan vs 82.1% placebo), although serious treatment-related adverse events were “numerically higher” for the emricasan groups (17.9% vs 11.9%, respectively). There were also 2% to 5% of patients in the emricasan groups with treatment-related adverse events who discontinued therapy versus 0% in the placebo.
Comment: The plan is to wait for the completion of the 48-week study.
Related news and insights
Chiesi Global Rare Diseases, a business unit of Chiesi Farmaceutici S.p.A., an international research-focused healthcare Group (Chiesi Group), announced that Health Canada has approved Ferriprox (deferiprone) for the treatment of iron overload in patients with sickle cell disease (SCD) or other anemias.
The Menarini Group and Radius Health announced positive topline results from the phase III EMERALD study evaluating RAD 1901 (elacestrant) as a monotherapy versus the standard of care (SoC) for the treatment of ER+/HER2- advanced or metastatic breast cancer (mBC).
Gilead Sciences, Inc. announced the FDA approved a new low-dose tablet dosage form of Biktarvy (bictegravir 30 mg/emtricitabine 120 mg/tenofovir alafenamide 15 mg tablets) for pediatric patients weighing at least 14 kg to less than 25 kg who are virologically suppressed or new to antiretroviral therapy.