LIB Therapeutics Submits BLA for Lerodalcibep Targeting Reductions in LDL-C

LIB Therapeutics Inc. has announced the submission of a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for lerodalcibep for the reduction of low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD) and primary hyperlipidemia.1

Announced on December 16, 2024, lerodalcibep is a novel, adnectin-based, small protein-binding, third-generation PCSK9 inhibitor. The drug is in development as a monthly, self-administered alternative to other approved PCSK9 inhibitors, with the potential for a single small-volume subcutaneous injection not requiring refrigeration at home or during travel.

“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-C levels with current oral therapies,” Evan Stein, founder, chief operating and scientific officer of LIB Therapeutics, said in a statement.1 “Lerodalcibep has demonstrated robust and sustained long-term LDL-C-lowering as well as enabling the vast majority of patients to achieve the more stringent lower LDL-C targets in global guidelines across clinical trials.”

LDL-C is a validated risk factor for ASCVD, the global leading cause of morbidity and mortality—CVD is expected to lead to more than 22 million deaths over the coming decades.2 Since the introduction of statins, evidence has shown reductions in all-cause CVD events, with further data pointing to greater event reductions with the PCSK9 inhibitor therapy class.

For patients with ASCVD who fail to meet LDL-C goals on maximally tolerated statins, or for those statin-intolerant, PCSK9s are recommended as an adjunctive therapy.

More than 2900 patients with CVD or without CVD at very high and high risk for CVD, including heterozygous (HeFH) and homozygous familial hypercholesterolemia (HoFH), were enrolled in the global Phase 3 LIBerate program.1 In key registration-enabling, placebo-controlled trials, This population received once-monthly lerodalcibep for up to 52 weeks.

Results from the Phase 3 LIBERATE-HeFH trial found the use of lerodalcibep resulted in mean placebo-adjusted LDL-C reductions of 65% at 24 weeks, with approximately 68% of patients achieiving LDL-C reductions of ≥50% and meeting European Society of Cardiology (ESC) guideline-recommended targets.3

In the LIBerate-HR trial, lerodalcibep achieved reductions in LDL-C levels by 56% more than placebo across 1 year in patients with or at very high risk for CVD.

More than 2400 patients continued in the 72-week open-label extension trial. This population continually maintained > 60% reductions (P <.0001) in LDL-C from baseline throughout the additional 72 weeks of open-label extension dosing.4 There were no signals of attenuation, including in those on Lerodalcibep for >2 years, according to LIB Therapeutics.

“Lerodalcibep offers a once-monthly, single small subcutaneous dose with excellent tolerability, combined with long ambient stability not requiring refrigeration by patients,” Stein added.1 “These factors are anticipated to achieve better patient adherence to the life-long treatment required to control LDL-C.”

In tandem with this announcement, LIB Therapeutics reported preparation to submit a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) by mid-2025.1 They indicated their plan to work with regulators to make lerodalcibep available globally, preparing organizational work for potential commercial launch in the future.

“Lerodalcibep is a potential best-in-class PCSK9 inhibitor that will enter a growing global PCSK9 market on target to reach $5B in 2025,” David Cory, chief executive officer of LIB Therapeutics, said in a statement.1 “Most importantly, lerodalcibep will introduce a patient-friendly treatment option to achieve the new guideline-directed, lower LDL-C goals.”

References

1. Lib Therapeutics submits a biologic license application to FDA for Lerodalcibep for the treatment of adults with elevated LDL-cholesterol. 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. Pokhrel B, Pellegrini MV, Levine SN. PCSK9 Inhibitors. [Updated 2024 Feb 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448100/
3. Campbell P. Lerodalcibep shows promise for HeFH in phase 3 liberate-hefh trial. HCP Live. August 30, 2023. Accessed December 19, 2024. https://www.hcplive.com/view/lerodalcibep-shows-promise-for-hefh-in-phase-3-liberate-hefh-trial
4. LIB Therapeutics Announce Positive Results from Lerodalcibep 72-Week Open-Label Extension Studies at American Heart Association 2024. LIB Therapeutics. November 18, 2024. Accessed December 19, 2024. https://cdn.prod.website-files.com/61e62faab82c326a4b4e92af/673bd0313462d3b1c033ef5e_2024%201118%20LIB%20AHA%202024%20PR.pdf.