The Food and Drug Administration (FDA) has approved Nexletol (bempedoic acid; Esperion) as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C).
Nexletol is a first-in-class adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers LDL-C by inhibiting cholesterol synthesis in the liver. The approval was based on data from two phase 3, multicenter, double-blind, placebo-controlled studies (CLEAR Harmony and CLEAR Wisdom) that evaluated the efficacy and safety of Nexletol in 3009 adult patients with HeFH and/or ASCVD as an add on to a maximally tolerated statin therapy for 52 weeks.
Results demonstrated that Nexletol provided a statistically significant lowering of LDL-C from baseline with a placebo-adjusted difference of -18% (95% CI, -20 to -16; P <.001) in CLEAR Harmony and -17% (95% CI, -21 to -14; P <.001) in CLEAR Wisdom; in both trials, the maximum LDL-C lowering effects occurred at week 4.
As for safety, the most common adverse reactions observed were upper respiratory tract infections, muscle spasms, hyperuricemia, back pain, abdominal pain or discomfort, bronchitis, pain in extremity, anemia, and elevated liver enzymes. In addition, the treatment has been associated with an increased risk of tendon rupture (0.5% of Nexletol-treated patients vs 0% of placebo-treated patients). Moreover, according to pharmacokinetic data, the administration of simvastatin or pravastatin with Nexletol may result in increased levels of the statins and related myopathy; concomitant simvastatin >20mg or pravastatin >40mg should be avoided.
“There are millions of patients who are unable to reach their LDL-C targets despite available medicines,” said 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. “Nexletol is the first oral, once-daily, non-statin treatment option for indicated patients in nearly 2 decades.”
Nexletol will be available on March 30, 2020 in 180mg strength tablets. Treatment is administered orally once daily and can be taken with or without food. Following initiation, lipid levels should be analyzed within 8 to 12 weeks.
For more information visit esperion.com.