Normal levels of apoptosis and caspase activity in healthy volunteers are not reduced by emricasan
Emricasan currently in Phase 2b study in acute-on-chronic liver failure and Phase 2 study in severe alcoholic hepatitis
Emricasan is a potent inhibitor of pro-apoptotic and pro-inflammatory caspases, and in prior Phase 1 and Phase 2 clinical trials, has been shown to rapidly suppress apoptotic caspase activity as determined by a key biomarker of inflammation and cell death, caspase cleaved CK18 (cCK18), in hepatitis C virus (HCV) patients to within ranges typically reported for healthy volunteers. Caspase activity is known to be elevated in many liver diseases and is associated with disease severity and progression. In the Phase 1 clinical trial, physiologically normal levels of apoptosis and pro-apoptotic caspase activity in healthy volunteers remained unaffected following exposure to emricasan.
"This novel observation provides important new information regarding the effect of pan caspase inhibition in healthy volunteers and further insight regarding the overall safety profile of emricasan," said
In the Phase 1 clinical trial, emricasan was administered to 15 healthy volunteers at a dose of either 25 mg single dose or 25 mg twice daily for 10 days as part of a 24 day drug-drug interaction study with cyclosporine. This dose was shown in prior clinical trials to provide near maximal reduction of elevated cCK18 and serum transaminases in HCV patients. In this trial, blood samples were taken on day 0 and on study days 1, 17- 20, 22 and 24-27. Serial blood samples were collected out to 12 hours post-dose on study days 1, 17 and 24. Both drug levels and cCK18 were measured at each time point. Emricasan had no effect on cCK18 levels in healthy volunteers at any time point in the trial. Drug exposure was consistent with previously reported blood levels.
Poster Presentation Details:
|Presentation Title:||"Physiologically normal levels of apoptosis in healthy volunteers are not|
|reduced by the pan caspase inhibitor, emricasan"|
|Location:||Poster Hall - Poster #1532|
|Session Title:||Hepatotoxicity: Apoptosis and Necrosis|