FDA OKs New Non-Statin, LDL-C Lowering Treatment

Esperion bempedoic acid (Nexletol) tablet has gained FDA approval for use in lowering low-density lipoprotein cholesterol (LDL-C) in adults with heterozygous familial hypercholesterolemia (HeFH) or fixed atherosclerotic cardiovascular disease (ASCVD), according to a company press release.

Bempedoic acid, an oral, once-daily, first-in-class ATP citrate lyase (ACL) inhibitor, is indicated for use as an adjunct to diet and maximally tolerated statin treatment.

The approval is based on data from the phase 3 LDL-C lowering program, which involved more than 3000 sufferers with more than 2000 sufferers handled with bempedoic acid.

A 52-week phase 3 trial evaluated the safety, adverse effect (AE) profile, and efficacy of bempedoic acid treatment when it was added to the use of maximally tolerated statins for one year. A total of 2230 patients were included, of whom 1488 were selected to receive bempedoic acid and 742 to placebo.

The Revealed Facts

Overall, the incidence of AEs in the bempedoic acid group (78.5%) and the placebo group (78.7%) did not differ considerably during the attack period. Nevertheless, the incidence of AEs leading to discontinuation of the regimen was higher in the bempedoic acid group than in the placebo group (10.9% versus 7.1%, respectively), as was the number of gouts (1.2% versus 0.3%, respectively), according to the data.

The study revealed that, at week 12, bempedoic acid decreased the mean LDL-C level by 19.2 mg per deciliter, representing a change of -16.5% from baseline.

A second study, the CLEAR Wisdom trial, evaluated the efficacy, long-term safety, and tolerability of bempedoic acid 180 mg versus placebo in 779 patients with ASCVD and HeFH inadequately controlled with current lipid-modifying therapies, added on to maximally-tolerated statin therapy, which may mean no statin at all.

The conclusions showed that bempedoic acid:3

• Significantly reduced LDL-C by 17% on background maximally-tolerated statin treatment at 12 weeks, with nearly all patients (85%) on moderate- or high-intensity statins, and the result was durable through 52 weeks.
• Significantly decreased high-sensitivity C-reactive protein by 19%, with a long-lasting effect through 52 weeks.
• Showed no worsening of hemoglobin A1c in sufferers with diabetes at 12 weeks.
• Showed overall AE rates comparable with placebo at 52 weeks, and the proportion of sufferers with reported severe AEs was similarly associated with placebo at 52 weeks.
• Showed adjudicated 3-component significant adverse cardiac event rates of 2.7% with bempedoic acid and 4.7% with placebo.

The most common AEs reported with bempedoic acid were upper respiratory tract infections, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes.1

All in All

“The FDA approval of Nexletol provides an outstanding option for patients living with elevated LDL-C and ASCVD or increased risk for cardiovascular disease because of HeFH,” Christie M. Ballantyne, MD, chairman of Esperion’s phase 3 Executive Committee and professor and chief of cardiology at Baylor College of Medicine in Houston, said in a statement.1 “There are millions of sufferers who are unable to reach their LDL-C targets despite available remedies. Nexletol is the first oral, once-daily, non-statin treatment option for indicated patients in nearly two decades.”