The CLEAR Harmony open-label extension study reports on the long-term effects of BA treatment for hypercholesterolemia.
Results from the CLEAR Harmony open-label extension (OLE) study demonstrated bempedoic acid (BA) to be safe and efficacious in adults with hypercholesterolemia, according to data presented at the European Society of Cardiology (ESC 2020) Congress.
The phase 3 CLEAR Harmony trial enrolled 2230 patients with either atherosclerotic cardiovascular disease (ASCVD), heterozygous familial hypercholesterolemia (HeFH), or both, and who were receiving stable, maximally tolerated statins. Patients were randomized 2:1 to receive either BA or placebo. Treatment dosage was 180 mg once daily for 52 weeks.
Results of the trial showed that BA significantly reduced LDL-C at week 12 when compared with placebo. Furthermore, the reduction was maintained for 52 weeks.
A team led by Christie Ballantyne, MD, Chief of Cardiology, Baylor College of Medicine, assessed the long-term effects of BA through week 72—followed by a 4-week follow-up period. Thus, the total exposure to treatment for patients was 2.5 years.
Of the patients who had completed the 52-week placebo controlled CLEAR Harmony study, 1462 immediately began the OLE. Patient randomization of 2:1 to either treatment groups was maintained for this study.
The investigators sought primary endpoints of long-term safety.
The population’s mean age at baseline was 66.9 years, and 73.9% were male. Up to 96.3% had ASCVD, 3.7% had HeHF with or without ASCVD.
In the original trial, patients’ baseline mean LDL-C was 102.9 mg/dL in the BA group and 99.0 mg/dL for placebo.
Overall, the observed LDL-C reduction from Clear Harmony baseline was -14.9% and -14.4% at weeks 12 and 72, respectively, of OLE treatment.
Treatment-emergent adverse events were reported in 1143 patients (78.2%), with 299 (20.5%) reporting serious cases.
Such events, which occurred at similar rates as the phase 3 CLEAR Harmony trial, consisted of creatine kinase elevations (1.8%), gout (2.6%), hepatic enzyme elevations (2.0%), hypoglycemia (1.2%), muscular disorders (8.5%), neurocognitive disorders (0.9%), new onset/worsening diabetes mellitus (5.5%), and renal disorders (2.8%).
The investigators also noted that biochemical changes were stable over the course of the extension study and returned to baseline levels after discontinuation of treatment.
A total of 114 patients (7.8%) experienced a treatment emergent adverse event that led to discontinuation of treatment. Conversely, as many as 1260 patients (86.25%) completed the 72 weeks of the extension study.
“Durable lipid lowering was observed through 78 weeks of BA treatment and patient adherence to BA therapy was high,” the investigators wrote. “Overall safety during the OLE was similar to results reported in the 52-week-long CLEAR Harmony study and the overall BA phase 3 clinical program, with no new safety findings.”
The study, “Long-term safety and efficacy of bempedoic acid in patients at high risk of atherosclerotic cardiovascular disease: results from the CLEAR Harmony open-label extension study,” was presented at ESC 2020.