"But don't all cardiac patients have elevated transaminase levels to start?"
BETonMACE already excludes patients with ALT/AST values greater than 1.5 times the upper limit of normal (ULN) at visit 1.
For more detail on the elevated ALT/AST data from the ASSURE study, see this document, which throughly documents adverse events and ALT/AST values from ASSURE. A summary of the ALT/AST observations in ASSURE is below (RVX000222=apabetalone):
"There were no clinically significant observations in laboratory results, with the exception of ALT/AST elevations, which occurred more frequently in the RVX000222 group compared with placebo (42.0% vs. 22.5%, p=0.002). In the RVX000222 group, 7.0% (17/243) had ALT elevations >3x ULN; among patients with any ALT elevation, 9.3% (9/97) had elevations >5x ULN. In the RVX000222 group, 4.1% (10/243) had AST elevations >3x ULN; among patients with any AST elevation, 7.0% (5/71) had elevations >5x ULN."
Also from the 2015 AGM (transcript courtesy of imtesty):
"We think we’re getting to the bottom of this adverse event. We’ve done a lot of work in the laboratory to investigate this. And we seem to see that there is a change in bile acid metabolism in selected patients, because BET inhibition does change the expression of bile transporters and bile enzymes in selected individuals. So there’s an increase in influx of cholesterol, and a change in bile pathway, and a down regulation, transient. But this down-regulation does not persist for long; there is an adaption within the liver cell, which accounts for why the enzyme levels go away with continued therapy. The net effect is an increase in bile acids in a very small number of patients. And we’re working in the lab to confirm this hypothesis. One of the reasons behind our BETonMACE study, apart from outcomes, is to get a very large safety database, to truly document the incidence and the consequences of these hepatic enzyme increases."
If interested, more tidbits on this apabetalone/aminotransferase/bile acid/FXR relationship in this post.
BearDownAZ
