The addition of the investigational drug lerodalcibep, a novel inhibitor of PCSK9, to standard cholesterol-lowering medication reduced LDL-cholesterol (LDL-C) levels by more than half among patients at high or very high risk for a myocardial infarction (MI) or stroke, according to results from the LIBerate-HR study presented during a Late-Breaking Clinical Trial session at ACC.24.

Researchers conducted a randomized, triple-blind, placebo-controlled study to evaluate the long-term efficacy and safety of lerodalcibep. The trial enrolled 922 patients (average age 64.5 years, 45% women; 77.9% White, 22.1% Black) in 11 countries. Over half of enrolled patients (52%) had not had an MI or stroke but were at high or very high risk; a quarter had diabetes and 10% had familial hypercholesterolemia. At baseline, the average LDL-C was 116 mg/dL, and 84% of patients were taking a statin (including high-intensity statin) and 17% were also taking ezetimibe.

Researchers randomized two-thirds of the patients to lerodalcibep 300 mg monthly and one-third to a matching placebo. All patients continued their diet and existing cholesterol-lowering medications. The primary endpoints were change in LDL-C at one year and average of LDL-C levels at weeks 50 and 52.

At one year, 824 patients (89%) had completed the study, with a similar dropout rate in both groups. Patients assigned to lerodalcibep achieved an average placebo-adjusted percentage reduction in LDL-C of between 56% (at week 52) and 63% (the average of weeks 50 and 52). More than 90% of patients in the lerodalcibep group achieved a reduction of ≥50% in LDL-C and attained the target LDL-C level for their risk group. In the placebo group, 16% of patients achieved both goals.

In the lerodalcibep group, apolipoprotein B was reduced by an average of 43% and levels of lipoprotein (a) fell by 33%.

No safety signals were observed. A mild or moderate reaction, such as redness, itching or bruising, at the site of the injection was the most common adverse event, affecting 6.9% of patients in the lerodalcibep group and 0.3% in the placebo group. However, the number of patients who withdrew from the trial due to these reactions was minimal and similar in both groups.

"These are the first long-term data for lerodalcibep, which show it to be both highly effective and safe after one year of follow-up," said Eric Quinton Klug, MBBCH, MMED, FACC, the study's lead author. "We have demonstrated persistent [LDL-C]-lowering efficacy over 52 weeks, with over 90% of patients achieving both a reduction greater than 50% and the new much lower LDL targets. In addition, lerodalcibep was well-tolerated, with minimal adverse effects."