SREBP inhibitor did not significantly lower LDL-c in phase 2a clinical trial
Results from a Phase 2a clinical trial that evaluated CAT-2054 treatment in hypercholesterolaemia patients showed that the agent not able to substantially decrease LDL-c levels, which was the primary end point of the study. CAT-2054 did show however beneficial effects for hypercholesterolaemia patients who are more likely to have non-alcoholic steatohepatitis (NASH), as determined by FIB-4 (Fibrosis-4).
CAT-2054 is an oral small molecule that inhibits Sterol Regulatory Element-Binding Protein (SREBP), which is a master regulator of the lipid metabolism. In this double-blinded trial, 153 hypercholesterolaemia patients who were on high-intensity statin were randomised to either placebo or 4 different arms of CAT-2054 (250 or 400 mg, once or twice daily) for 4 weeks, after a 4-week run-in on atorvastatin 40 mg.
All 4 doses were generally well tolerated and 94.8% of patients completed the trial. The maximum LDL-c decrease observed was 7.1% with CAT-2054 versus 4.5% with placebo. Also triglycerides and non-HDL-c did not change significantly.
A potentially favourable pattern in liver function tests (LFTs) was seen in a subset of patients who were more likely to have NASH (n = 51). There was a mean reduction of ALT 3.0 IU/mL and AST 2.8 IU/mL across all dosing arms of CAT02054, compared to a reduction of ALT 0.2 IU/mL and AST ALT 0.2 IU/mL with the placebo arm (mean baseline ALT 26 and AST 25 IU/mL respectively). As LFT values were relatively low at baseline and duration of the trial was short, this needs further investigation.
The company does not expect to invest further in CAT-2054 for hypercholesterolaemia but plans to complete additional data analysis and to determine the best path forward for CAT-2054 in NASH.
Source: Press release Catabasis June 7, 2016