Cholesterol synthesis inhibitor meets primary safety and tolerability endpoints in phase III trialNews - May 2, 2018
Positive top-line results have been published from the pivotal phase 3 study (Study 1 or 1002-040) evaluating the long-term safety, tolerability and efficacy of bempedoic acid 180 mg, versus placebo in high-risk patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia (HeFH) who are inadequately controlled with current lipid-modifying therapies, including maximally tolerated statin therapy.
The study included 2,230 patients and met the primary endpoint of safety and tolerability. The study was conducted at 117 sites in the U.S., Canada and Europe. Patients were randomized 2:1 to receive bempedoic acid or placebo. In this 52-week study, bempedoic acid was observed to be safe and well-tolerated. There were no clinically relevant differences between the bempedoic acid and placebo groups in the occurrence of adverse events (AEs) with 78.5% and 78.7%, respectively; or serious adverse events (SAEs) with 14.5% and 14.0%, respectively. Discontinuations due to AEs were 10.9% and 7.1%, respectively for the bempedoic acid and placebo groups; discontinuations due to muscle-related AEs were 2.2% and 1.9%, respectively in the bempedoic acid and placebo groups.
In the study, 0.54% of patients treated with bempedoic acid and 0.13% of patients in the placebo group had elevations in liver function tests (ALT/AST) of greater than three times the upper limit of normal (>3 ULN), repeated and confirmed. The cumulative number of patients now treated with bempedoic acid in phase 2 and phase 3 clinical trials totals 2,434. Of these, 0.58% had elevations in liver function tests >3 ULN, repeated and confirmed. This rate of elevations in liver function test is consistent with the rate observed in all other previously approved oral LDL-C-lowering therapies, including statins and ezetimibe.
The key secondary, efficacy endpoint was also met, with on-treatment LDL-C lowering of an additional 20% at 12 and 24 weeks (p<0.001) (18% (p<0.001) in the intent to treat analysis) and 16% at 52 weeks (p<0.001). Patients treated with bempedoic acid also achieved a significant reduction of 22% in high-sensitivity C-reactive protein (hsCRP), compared to the placebo group which had an increase of 3% (p<0.001).
Full results from this study are anticipated to be presented at an upcoming medical conference and to publish in a major medical journal. An open-label extension study (1002-050) was initiated in early 2017 and is fully enrolled with 1,462 patients.