Esperion announced positive results today for the first in a series of pivotal phase 3 studies of its cholesterol lowering drug.
The trial (Study 4, or 1002-048) compared bempedoic acid to placebo in 269 patients with atherosclerotic cardiovascular disease (ASCVD) or at high risk for ASCVD who have high LDL cholesterol levels (100 mg/dl or greater) despite treatment with ezetimibe. Patients were also either taking a low starting dose of a statin or no statin at all.
After 12 weeks the study met its primary endpoint, showing a significant reduction in LDL levels in the bempedoic acid group. LDL cholesterol was reduced by 23% in the treatment group and increased by 5% in the placebo group, resulting in a 28% difference between the groups. Esperion also reported that patients in the treatment group “achieved a significantly greater reduction of 32 percent in high-sensitivity C-reactive protein (hsCRP), an important marker of the underlying inflammation associated with cardiovascular disease, compared to the placebo group which had an increase of two percent (p<0.001).”
The company reported that their drug “was observed to be safe and well-tolerated” in the study. Two patients in the treatment group had elevated liver function tests. The company said the overall rate of liver function increase in clinical trials has been consistent with other cholesterol drugs, including statins and ezetimibe.
Esperion said that it expects to report results from 4 additional pivotal studies this year, including 2 studies in 3,000 patients taking maximally-tolerated statins, 2 studies in 600 statin-intolerant patients, and one study combining bempedoic acid and ezetimibe in 350 patients taking maximally-tolerated statins. The company had previously announced the initiation in December 2016 of a large cardiovascular outcomes trial (CVOT) including more than 12,000 patients. Results from that trial, known as CLEAR OUTCOMES, won’t be available until 2022.
Esperion executives recently told Bloomberg News that the company plans to compete with the more powerful LDL lowering PCSK9 inhibitors by charging much less for their drug. At $9-10 dollars per day the drug would cost less than $4,000 a year, which is less than a third of the list price and less than half of the typical discounted price of the PCSK9 inhibitors. Esperion CEO Tim Mayleben said that many people with elevated LDL levels could reach target levels with bempedoic acid and do not require a PCSK9 inhibitor.
Several experts I contacted said the results were expected. James Stein (University of Wisconsin) said that he is “always happy to learn that a new drug with a new mechanism of action lowered LDL-C safely. The observed reductions in LDL-C and hsCRP are clinically important. If the drug shows durable reduction in LDL-C in more patients over a longer period of time and continues to show a favorable safety profile, it could become an important part of our tool kit for treating dyslipidemia. I Iook forward to the results of the rest of the phase III program.”
Sanjay Kaul (Cedars-Sinai) said the trial was “a positive small first step.” He wanted to find out more about the baseline LDL levels, but said that “the magnitude of LDL reduction is greater than what we see with ezetimibe (typically 16-18% relative reduction).”
“At $10 per day for the oral pill, this looks promising,” said Kaul. “Of course, the proof of the pudding lies in the outcome trials!”