About 4 million Americans can’t tolerate statins. A new study suggests bempedoic acid could be used to help these patients lower their LDL cholesterol.
Ulrich Laufs, MD, PhD
For patients with elevated low-density lipoprotein cholesterol, statin medications are the standard of care. That’s a problem for the millions of people considered statin intolerant. Now, new research suggests an alternative treatment may be able to successfully help lower LDL cholesterol (LDL-C) in these patients, without the use of statins.
This month Daiichi Sankyo and its partner, Esperion Therapeutics, announced the results of the companies’ phase 3, double-blind study of bempedoic acid for the treatment of high LDL cholesterol. The placebo-controlled CLEAR Serenity study showed the treatment lowered LDL-C by 21% after 12 weeks.
“In the challenging group of patients with statin intolerance, CLEAR Serenity demonstrates that bempedoic acid reduced LDL-C significantly more than placebo,” said corresponding author Ulrich Laufs, MD, PhD, of Leipzig University, in a press release.
Esperion’s senior director of investor relations Alex Schwartz told MD Magazine® that about 4 million Americans—roughly 1 in 10 people with diagnosed elevated LDL-C—are unwilling or unable to take statins due to real or perceived side effects. These side effects often take the form of muscle tenderness, aching, or myalgia. In the CLEAR Serenity study, rates of muscle-related adverse events in the bempedoic acid group were not significantly different from the complaint rate in the placebo group.
Bempedoic acid is a prodrug that works by inhibiting ATP‐citrate lyase. In the study, it was delivered in a once-daily 180 mg oral dose. A total of 345 patients were enrolled in the study, spread over 67 sites in the United States and Canada. In order to be eligible for the study, a patient had to have reported intolerance to at least 2 statins, including at least 1 at the lowest available dose. Two-thirds of patients in the study were put on bempedoic acid, while the remaining third were given the placebo. At 12 weeks, LCL-C improved by -21.4% compared to placebo (95% CI, −25.1% to −17.7%; P <0.001). Reductions were also reported in non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein.
“These results demonstrate bempedoic acid could offer a well-tolerated and effective oral therapeutic option especially for the millions of patients needing LDL-C lowering but have difficulty tolerating statin treatment due to muscle-related side effects," Laufs said.
Schwartz said the companies aren’t positioning bempedoic acid to be a replacement for statins. If approved, the therapy could be used alongside the highest tolerable dose of statins in patients who can tolerate at least a low dose.
However, Schwartz also said there is evidence that bempedoic acid could be helpful in prediabetics and patients seeking to reduce HbA1c. Bempedoic acid has been shown to reduce HbA1c, and, when used with a statin, lower the frequency of diabetes disease onset or worsening.
“While bempedoic acid will not be replacing the statin, a physician might reach for a lower intensity statin (versus a high intensity statin where HbA1c effects are the most pronounced) and look to add bempedoic acid on earlier to help the patient achieve their LDL-C lowering threshold (and better avoid HbA1c increases and worsening/new onset diabetes),” he said.
The study, “Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia and Statin Intolerance,” was published in the Journal of the American Heart Association.