FDA Receive a Biologic License Application for Lerodalcibep, a Novel LDL-C-Lowering Drug

A biologic license application (BLA) for lerodalcibep (LIB003; LIB Therapeutics), a novel PCSK9 inhibitor, was submitted to the FDA for treatment of patients with atherosclerotic cardiovascular disease (ASCVD), or very high or high risk of ASCVD, and primary hyperlipidemia, including heterozygous and homozygous familial hypercholesterolemia (HeFH / HoFH).¹

HDL and LDL molecules | Image Credit: © Ratchada - stock.adobe.com

ASCVD remains the leading cause of morbidity and mortality around the globe, accounting for approximately 24 million Americans in 2019, and that number continues to rise. According to various studies, high cholesterol is a major risk factor and is almost exclusively associated with ASCVD, making management of LDL-C essential for prevention and treatment of the disease.^2-4

The BLA submission is supported by data from 5 phase 3 global trials known as the LIBerate program, which are evaluating the safety and efficacy of lerodalcibep. The studies consist of over 2300 patients on maximally tolerated statin and other oral agents, requiring additional LDL-C reduction. Lerodalcibep is a novel, adnectin-based, small protein-binding, third-generation PCSK9 inhibitor that has demonstrated success in lowering LDL-C. It is administered as a subcutaneous injection once monthly for up to 52 weeks, as recommended by the trial investigators.¹

Lerodalcibep’s capabilities were demonstrated in the global, double-blind, placebo-controlled, phase 3 LIBERATE-HR trial (NCT04806893). According to the data, 90% of patients receiving lerodalcibep achieved a 50% or greater reduction in LDL-C, as well as lower levels of atherogenic lipids and apolipoproteins including non-high density lipoprotein cholesterol (47.3%), very LDL-C (25.9%), apolipoprotein B (43%), lipoprotein(a) (30%), and triglycerides (14.1%). The investigators reported that lerodalcibep was well tolerated with comparable adverse events to patients receiving placebo, which primarily consisted of mild to moderate irritation at the injection site.²

“There remains a large unmet need among millions of patients with cardiovascular disease, or at high cardiovascular risk, including the 30 million people with inherited high cholesterol, who are unable to reach optimal LDL cholesterol levels with current oral therapies,” Evan Stein, MD, founder, chief operating and scientific officer of LIB Therapeutics, said in a press release. "Lerodalcibep has demonstrated robust and sustained long-term LDL cholesterol-lowering as well as enabling the vast majority of patients to achieve the more stringent lower LDL-cholesterol targets in global guidelines across clinical trials. Lerodalcibep also offers a once-monthly, single small subcutaneous dose with excellent tolerability, combined with long ambient stability not requiring refrigeration by patients. These factors are anticipated to achieve better patient adherence to the life-long treatment required to control LDL cholesterol.”¹

REFERENCES

1. LIB Therapeutics submits a biologic license application to FDA for lerodalcibep for the treatment of adults with elevated LDL-cholesterol. News release. Business Wire. December 16, 2024. Accessed December 19, 2024. https://www.businesswire.com/news/home/20241216448140/en/LIB-Therapeutics-Submits-a-Biologic-License-Application-to-FDA-for-Lerodalcibep-for-the-Treatment-of-Adults-with-Elevated-LDL-Cholesterol

2. Gerlach A. Lerodalcibep delivers significant LDL-C reduction for high-risk cardiovascular patients. Pharmacy Times. November 7, 2024. Accessed December 19, 2024. https://www.pharmacytimes.com/view/lerodalcibep-delivers-significant-ldl-c-reduction-for-high-risk-cardiovascular-patients

3. Gu J, Sanchez R, Chauhan A, et al. Lipid treatment status and goal attainment among patients with atherosclerotic cardiovascular disease in the United States: a 2019 update. Am J Prev Cardiol. March 20, 2022. doi:10.1016/j.ajpc.2022.100336

4. Mortensen M, Dzaye O, Bøtker H, et al. Low-density lipoprotein cholesterol is predominantly associated with atherosclerotic cardiovascular disease events in patients with evidence of coronary atherosclerosis: The Western Denmark Heart Registry. Circulation. January 9, 2023. doi:10.1161/CIRCULATIONAHA.122.061010