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

Esperion’s bempedoic acid (Nexletol) tablet has received FDA approval for use in lowering low-density lipoprotein cholesterol (LDL-C) in adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD), according to a company press release.¹

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 therapy.¹

The approval is based on data from the phase 3 LDL-C lowering program, which included more than 3000 patients with more than 2000 patients treated with bempedoic acid.¹

A 52-week phase 3 trial assessed the safety, adverse effect (AE) profile, and efficacy of bempedoic acid therapy when it was added to the use of maximally tolerated statins for 1 year. A total of 2230 patients were included, of whom 1488 were assigned to receive bempedoic acid and 742 to placebo.²

Overall, the incidence of AEs in the bempedoic acid group (78.5%) and the placebo group (78.7%) did not differ substantially during the intervention period. However, 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 incidence of gout (1.2% versus 0.3%, respectively), according to the data.²

The study showed that, at week 12, bempedoic acid reduced the mean LDL-C level by 19.2 mg per deciliter, representing a change of -16.5% from baseline.²

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/or HeFH inadequately controlled with current lipid-modifying therapies, added on to maximally-tolerated statin therapy, which may mean no statin at all.³

The findings showed that bempedoic acid:³

• Significantly lowered LDL-C by 17% on background maximally-tolerated statin therapy at 12 weeks, with nearly all patients (85%) on moderate- or high-intensity statins, and the effect was durable through 52 weeks.

• Significantly lowered high-sensitivity C-reactive protein by 19%, with a durable effect through 52 weeks.

• Showed no worsening of hemoglobin A1c in patients with diabetes at 12 weeks.

• Showed overall AE rates comparable with placebo at 52 weeks, and the proportion of patients with reported serious AEs was similar compared with placebo at 52 weeks.

• Showed adjudicated 3-component major 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

“The FDA approval of Nexletol provides an important 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 patients who are unable to reach their LDL-C targets despite available medicines. Nexletol is the first oral, once-daily, non-statin treatment option for indicated patients in nearly 2 decades.”

Bempedoic acid will be commercially available on March 30, 2020, according to Esperion.¹

References:

1. Esperion Announces FDA Approval of NEXLETOL (bempdoic acid) Tablet, an Oral, Once-Daily, Non-Statin LDL-Cholesterol Lowering Medicine [news release]. Esperion’s website. https://www.esperion.com/investors-media/press-releases/. Accessed February 24, 2020.

2. Ballantyne CM, Ray KK, Bays HE, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. The New England Journal of Medicine. March 14, 2019. Doi: 10.1056/NEJMoa1803917

3. Goldberg AC, Leiter LA, Stroes ES, et al. Effect of bempedoic acid vs placebo added to maximally tolerated statins on low-density lipoprotein cholesterol in patients at high risk for cardiovascular disease. JAMA. 2019. Doi: 0.1001/jama.2019.16585