FDA Accepts Lerodalcibep BLA for LDL-C Reduction in High-Risk Patients

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for lerodalcibep targeting reductions in low-density lipoprotein cholesterol (LDL-C) levels in a patient population with or at high risk for atherosclerotic cardiovascular disease (ASCVD) and primary hyperlipidemia.¹

Announced by LIB Therapeutics Inc. on February 10, 2025, the FDA set a Prescription Drug User Fee Act (PDUFA) action date of December 12, 2025, with no plans to hold an advisory committee meeting. The BLA for lerodalcibep was supported by 5 global Phase 3 registrational studies in the LIBerate program.

“There remains a large unmet need among millions of patients with CVD, or at high cardiovascular risk, including the 30 million people with inherited high cholesterol, who are unable to achieve currently recommended guideline-directed goals for LDL-C with current oral therapies,” said Evan Stein, MD, co-founder and chief operating and scientific officer of LIB, in a statement. “Lerodalcibep has demonstrated robust and sustained long-term LDL-C-lowering, enabling the vast majority of patients to achieve these more stringent lower LDL-C targets with excellent safety and adherence across clinical trials.”

A novel, adnectin-based, small protein-binding, third-generation PCSK9 inhibitor, LIB Therapeutics developed lerodalcibep as a single small-volume, subcutaneous injection alternative to approved PCSK9 drugs. Citing its unique patient-friendly, once-monthly self-administration, the company indicated that lerodalcibep does not require refrigeration at home or during travel.¹

The BLA for lerodalcibep was submitted to the FDA in December 2024, based on positive results from the global Phase 3 LIBerate program. These trials included 2900 patients with CVD or at very high or very high risk for CVD, including patients with heterozygous (HeFH) and those aged >10 years with homozygous familial hypercholesterolemia (HoFH). Across key registration-enabling, placebo-controlled trials, patients received once-monthly lerodalcibep for up to 52 weeks.²

Results from the Phase 3 LIBERATE-HeFH trial showed mean placebo-adjusted LDL-C reductions of 65% with lerodalcibep at 24 weeks. Approximately 68% of patients achieved LDL-C reductions ≥50%, meeting European Society of Cardiology (ESC) guideline-recommended targets.³ In the LIBerate-High Risk (HR) trial, lerodalcibep achieved 56% greater reductions in LDL-C levels than placebo across 1 year in patients with or at very high risk for CVD.

From these trials, a population of 1468 patients with or at very high risk for CVD and 703 patients with HeFH continued into the 72-week LIBerate open-label extension (OLE) trial

Patients with or at very high risk for CVD maintained > 60% reductions (P <.0001) in LDL-C from baseline throughout the additional 72 weeks of open-label extension lerodalcibep dosing, without signs of attenuation. Those with HeFH maintained 50% to 53% (P<0.0001), with 72 to 76 mg/dL absolute, reductions in LDL-C across the 72 weeks with no signals of attenuation.⁴

LIB Therapeutics announced that, following the FDA BLA filing, they anticipate submitting Marketing Authorization Application to the European Medicines Agency (EMA) in Q2 2025.¹

“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-firendly treatment option to achieve the new lower LDL-C goals,” said David Cory, chief executive officer of LIB Therapeutics, in a statement.¹ “The LIB operating team is now focused on Lerodalcibep US commercial launch preparation.”

References

1. Lib Therapeutics announces FDA acceptance of biologics license application for Lerodalcibep to lower LDL-cholesterol across broad patient population. Business Wire. February 10, 2025. Accessed February 10, 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. Iapoce C. Lib Therapeutics submits bla for Lerodalcibep targeting reductions in LDL-C. HCP Live. December 19, 2024. Accessed February 10, 2025. https://www.hcplive.com/view/lib-therapeutics-submits-bla-for-lerodalcibep-targeting-reduction-in-ldl-c.

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.