LDL-C-Lowering Therapy Lerochol Gains FDA Approval

The Food and Drug Administration (FDA) has approved Lerochol^TM (lerodalcibep-liga) as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH).

Lerochol is an adnectin-based, small protein-binding, third generation proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. It is designed for self-administration as a once-monthly subcutaneous (SC) injection and is room temperature stable for up to 3 months.

The approval was supported by data from 3 randomized, double-blind, placebo-controlled trials that enrolled 2017 adults with HeFH, clinical atherosclerotic cardiovascular disease (ASCVD), or increased risk of ASCVD, who were on a stable low-fat, low-cholesterol diet and maximally tolerated statin therapy and who required additional LDL-C lowering.

The LIBerate-CVD (ClinicalTrials.gov Identifier: NCT04797247) and LIBerate-HR (ClinicalTrials.gov Identifier: NCT04806893) trials were both 52-week studies in which 1844 adults with ASCVD or at increased risk of ASCVD events were randomly assigned 2:1 to receive lerodalcibep 300mg (n=1229) or placebo (n=615) by SC injection every 4 weeks. 

Findings from LIBerate-CVD showed the mean percentage change in LDL-C from baseline at week 52 was -55% with lerodalcibep vs -0.1% with placebo (difference, -55% [95% CI, -59.2%, -50.8%]; P <.0001). In LIBerate-HR, the difference between the lerodalcibep and placebo groups in mean percentage change in LDL-C from baseline to week 52 was -50% (95% CI, -54.2%, -45.2%; P <.0001).

In LIBerate-FH (ClinicalTrials.gov Identifier: NCT04797104), 478 patients with HeFH were randomly assigned 2:1 to receive lerodalcibep 300mg (n=319) or placebo (n=159) by SC injection every 4 weeks. At 24 weeks, the difference between the lerodalcibep and placebo groups in mean percentage change in LDL-C from baseline was -59% (95% CI, -65.7%, -51.7%; P <.0001).

The most common adverse reactions reported with lerodalcibep were injection site reactions, nasopharyngitis, diarrhea, nausea, and peripheral edema. 

Lerochol is supplied as a 300mg/1.2mL single-dose prefilled syringe for SC injection. The recommended dosage is 300mg once monthly. Patients or caregivers may administer the treatment following training on appropriate SC injection technique.  

According to LIB Therapeutics, Lerochol prefilled syringes will be available in the spring of 2026. An updated autoinjector device is in the works and is expected later in the year.