FDA Accepts BLA for Lerodalcibep, a Novel Agent to Lower LDL-Cholesterol in Atherosclerotic Cardiovascular Disease

The FDA has accepted for review the biologics license application (BLA) of lerodalcibep (LIB Therapeutics) to reduce low-density lipoprotein cholesterol (LDL-C) in the treatment of patients with atherosclerotic cardiovascular disease (ASCVD), or very high or high risk of ASCVD, and primary hyperlipidemia, including heterozygous patients and those 10 years or older with homozygous familial hypercholesterolemia (HeFH/HoFH), according to a news release from LIB Therapeutics.¹

Low-density lipoprotein cholesterol can lead to cardiovascular complications. | Image Credit: © Superrider - stock.adobe.com

The BLA was submitted to the FDA in late 2024, supported by data from multiple phase 3 clinical trials that have evaluated the efficacy and safety of lerodalcibep. The novel, adnectin-based, small protein-binding, third-generation PCSK9 inhibitor was developed as a more convenient alternative to other approved PCSK9 inhibitors. Lerodalcibep is designed as a once-monthly, self-administered, subcutaneous injection, making treatment administration and adherence easier for patients. The addition of adnectin as the anti-PCSK9 binding domain of lerodalcibep engineers the drug for high-affinity, sub-nanomolar binding to human PCSK9. The fusing of adnectin to human serum albumin enhances the half-life of lerodalcibep.^1,2

"Lerodalcibep has demonstrated robust and sustained long-term LDL cholesterol-lowering, enabling the vast majority of patients to achieve these more stringent lower LDL-cholesterol targets with excellent safety and adherence across clinical trials,” Evan Stein, MD, chief operating and scientific officer of LIB Therapeutics, said in the news release.¹

The phase 3 trials that have investigated lerodalcibep are collectively known as the LIBerate Program, which includes 5 studies encompassing over 2900 patients—including 2300 patients that were on maximally tolerated statin and other oral agents that required further LDL-C reductions. In these trials, lerodalcibep was dosed once monthly for up to 52 weeks, with over 2400 patients having continued treatment in the 72-week open-label extension study.¹

In the LIBERATE-HR trial (NCT04806893), lerodalcibep led to significant reductions of LDL-C in patients with cardiovascular disease (CVD) or those at high risk of CVD, supporting the long-term use of the drug in patients who are struggling to adequately reduce their LDL-C levels on statins alone. Most patients receiving lerodalcibep (90%) achieved a 50% or greater reduction in LDL-C compared with patients on placebo, while also leading to significant reductions in other atherogenic lipids and apolipoproteins.³

Furthermore, lerodalcibep was well-tolerated among enrolled patients, with any treatment-emergent adverse events (TEAEs) that arose being comparable in their incidence with the placebo group, according to the investigators. The most frequently reported TEAEs in the lerodalcibep group were mild or moderate injection site reactions, none of which resulted in treatment discontinuation.³

“Lerodalcibep is a potential best-in-class PCSK9 inhibitor with a once-monthly, single small-volume subcutaneous dose, combined with long ambient stability not requiring refrigeration at home or in travel, offering a more patient-friendly treatment option to achieve the new lower LDL-C goals,” David Cory, CEO of LIB Therapeutics, said in the news release.¹

The FDA, which is not currently planning to hold an advisory committee meeting to discuss LIB Therapeutic’s application, has set a Prescription Drug User Fee Act action date of December 12, 2025.¹

REFERENCES

1. LIB Therapeutics. LIB Therapeutics announces FDA acceptance of biologics license application for lerodalcibep to lower LDL-cholesterol across broad patient population. News Release. Released February 10, 2025. Accessed February 11, 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

2. Gerlach A. FDA receive a biologic license application for lerodalcibep, a novel LDL-C-lowering drug. Pharmacy Times. Published December 19, 2024. Accessed February 11, 2025. https://www.pharmacytimes.com/view/fda-receive-a-biologic-license-application-for-lerodalcibep-a-novel-ldl-c-lowering-drug

3. Gerlach A. Lerodalcibep delivers significant LDL-C reduction for high-risk cardiovascular patients. Pharmacy Times. Published November 7, 2024. Accessed February 11, 2025. https://www.pharmacytimes.com/view/lerodalcibep-delivers-significant-ldl-c-reduction-for-high-risk-cardiovascular-patients