FDA Approves Lerodalcibep-liga (Lerochol) for LDL-C Reduction in Hypercholesterolemia

Announced by parent company LIB Therapeutics on December 15, 2025, the US Food and Drug Administration (FDA) has approved lerodalcibep-liga (Lerochol) injection for subcutaneous use as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH).1

“The primary challenge in lipid management today is helping patients achieve and maintain the increasingly stringent LDL-C targets in current guidelines,” Dean Kereiakes, MD, chairman of The Christ Hospital Heart and Vascular Institute and professor of Medicine at the University of Cincinnati, said in a statement.1 “While PCSK9 inhibitors as a class deliver powerful cholesterol lowering potential, LEROCHOL was designed to address the barriers that have limited their use, including ease of use features like a single small monthly injection, self-administered at home with extended room-temperature stability for home storage and travel. For patients with cardiovascular disease who require lifelong cholesterol management, LEROCHOL offers an important addition to our treatment options.”

Lerodalcibep is a novel, small protein-binding, third-generation PCSK9 inhibitor in development as a once-monthly, single small-volume subcutaneous injection for LDL-C lowering. Its anti-PCSK9 binding domain is adnectin, an 11-kDa polypeptide designed for high-affinity subanomolar binding to human PCSK9 and fused to human serum albumin to increase plasma half-life. Additionally, lerodalcibep does not require refrigeration, separating it from all approved PCSK9 inhibitors.2

The FDA’s decision was based on results from the LIBerate program, a series of 5 global phase 3 registration studies including 2900 patients. Most recently, the LIBerate-HoFH phase 3 trial, published in January 2025, compared lerodalcibep to evolocumab for the treatment of homozygous familial hypercholesterolemia (HoFH). The study consisted of 2 24-week treatment periods separated by an 8-week washout, conducted in 12 lipid clinics in 6 countries.3

Patients were aged ≥10 years and had genetically confirmed HoFH. Included patients were randomly assigned to either lerodalcibep 300 mg monthly or evolocumab 420 mg monthly for 24 weeks (period A), followed by an 8-week washout before being swapped to the alternate treatment for the next 24 weeks (period B). The primary efficacy endpoint was the percent change from baseline in LDL cholesterol concentration to week 24 for both period A and B. The intent-to-treat (ITT) population consisted of all randomly assigned patients, and the safety population included all patients who received any study medication.3

Ultimately, 82 patients were screened, and 6 entered period A. Mean age was 28.7 years (standard deviation [SD], 15.2), and 20 of 66 were pediatric patients. Mean baseline LDL cholesterol was 10.59 mmol/L (SD, 4.37). By week 24, mean LDL cholesterol reduction by ITT analysis was -4.9% on lerodalcibep compared to -10.3% on evolocumab, with a mean difference between treatments of 5.4% (95% CI, -0.2 to 11.1).3

When averaged across all monthly visits, LDL cholesterol response was -9.1% on lerodalcibep and -10.8% on evolocumab. Both drugs were well tolerated and exhibited no treatment-related serious adverse events. Injection site reactions were reported in 1 of 66 patients on lerodalcibep and 15 of 62 on evolocumab. Investigators determined that these results indicate lerodalcibep’s noninferiority to evolocumab.3

“[Lerodalcibep-liga] was designed for patients who need life-long treatment to achieve and maintain the new lower LDL-C goals especially those with cardiovascular disease and the millions with inherited high cholesterol (familial hypercholesterolemia or FH). We look forward to bringing [lerodalcibep-liga] to patients in the coming months," Evan Stein, MD, PhD, Founder, CEO and Chief Scientific Officer of LIB Therapeutics, said in a statement.1

References

1. LIB Therapeutics. U.S. Food and Drug Administration Approves LIB Therapeutics’ LEROCHOL™ (lerodalcibep-liga) for Adults with Elevated LDL Cholesterol. December 15, 2025. Accessed December 15, 2025. https://www.businesswire.com/news/home/20251215907781/en/U.S.-Food-and-Drug-Administration-Approves-LIB-Therapeutics-LEROCHOL-lerodalcibep-liga-for-Adults-with-Elevated-LDL-Cholesterol

2. Choong I. LIB Therapeutics Announces FDA Acceptance of Biologics License Application for Lerodalcibep to Lower LDL-Cholesterol Across Broad Patient Population. BusinessWire. February 10, 2025. Accessed December 9, 2025. https://www.businesswire.com/news/home/20250210806330/en/LIB-Therapeutics-Announces-FDA-Acceptance-of-Biologics-License-Application-for-Lerodalcibep-to-Lower-LDL-Cholesterol-Across-Broad-Patient-Population

3. Raal FJ, Mehta V, Kayikcioglu M, et al. Lerodalcibep and evolocumab for the treatment of homozygous familial hypercholesterolaemia with PCSK9 inhibition (LIBerate-HoFH): a phase 3, randomised, open-label, crossover, non-inferiority trial. Lancet Diabetes Endocrinol. 2025;13(3):178-187. doi:10.1016/S2213-8587(24)00313-9