ACC 2024: Adding investigative lerodalcibep to cholesterol lowering treatment shows significant efficacy

By adding investigational lerodalcibep to their standard cholesterol-lowering treatment for a year, patients at high risk for a heart attack or stroke achieved a reduction of “bad” cholesterol (LDL) of more than half when compared with  placebo.

And 90% of the subjects in the LIBerate-HR trial who were treated with lerodalcibep reached the new, more challenging LDL targets set by the American College of Cardiology (ACC), compared to 16% for placebo-treated subjects.

The findings were presented at ACC’s Annual Scientific Session on Sunday, April 7. 2024.

“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 lead author Eric Klug, MBBCh, MMed, of the University of Witwatersrand in Johannesburg, South Africa. “We have demonstrated persistent LDLcholesterol-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,” he said.

As background the authors noted that lerodalcibep is a novel inhibitor of PCSK9, a liver protein that inhibits the clearance LDL cholesterol from the body.

Lerodalcibep is administered as a low-dose (1.2 mL) monthly injection. Notably, it can be self-administered.

The investigators enrolled 922 subjects with cardiovascular disease (CVD), or at very-high or high risk for CVD, who were being treated with maximally tolerated statin therapy.

At baseline, subjects at very-high or high risk for, but without, CVD, were 52% of the 922 subjects, and 25% of the total trial group had been diagnosed with diabetes, with mean LDL-C of 116.3 mg/dL at baseline.

The investigators randomized the subjects to lerodalcibep or placebo for 52 weeks. Two-thirds received monthly treatment of 300 mg (1.2 mL) of lerodalcibep and one-third received a monthly dose of matching placebo.

Both groups continued their diet and existing cholesterol-lowering medications

 

Primary endpoints were LDL-C percent change from baseline to Week 52 and the mean of Weeks 50 and 52.

At one year, 824 patients (89%) had completed the trial. There was a similar dropout rate in both the lerodalcibep and placebo cohorts.

Subjects treated with lerodalcibep achieved a reduction in LDL cholesterol of between 56% (at week 52) and 63% (the average of weeks 50 and 52).

Over 90% of patients in the lerodalcibep group achieved a reduction of 50% or more in their LDL cholesterol levels and reached the target LDL cholesterol level for their risk group during the study.

In the placebo group, only 16% of patients achieved both goals.

Among lerodalcibep-treated subjects, levels of apolipoprotein B, a protein that carries LDL cholesterol through the body, fell by an average of 43%. And lipoprotein (a), another “bad” cholesterol variant that elevates cardiovascular risk, fell by 33%.

“Age, gender, race, body mass index, baseline LDL cholesterol level, intensity of statin use, presence of diabetes or FH [Familial hypercholesterolemia] —none of these factors altered the outcome favoring lerodalcibep,” Klug said.

Klug added, “Statins are, and should continue to be, the foundation for reducing LDL cholesterol levels, as they are well proven over the last 30 years to reduce risk for heart disease and strokes. For many patients, however, even taking the maximum dose of a statin that they can tolerate, as well as additional non-statin oral agents, does not reduce their LDL cholesterol to a low-risk level.”

Subjects who participated in the LIBerate-HR trial are now receiving lerodalcibep, and they will be evaluated after one year.