FDA Approves Once-Monthly PCSK9 Injection for LDL-C Reduction

The FDA has approved subcutaneous lerodalcibep-liga (Lerochol; LIB Therapeutics) as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH).¹

The once-monthly, self-administered PCSK9 inhibitor is expected to become available in the US in spring 2026, according to a LIB Therapeutics news release. The drug developer said the approval was based on findings from LIBerate-004 (NCT04797104), one of the studies in its global Phase 3 LIBerate Program.^1,2

“We founded LIB Therapeutics with a mission to bring an effective and more patient-friendly treatment option to the millions of patients who still need additional LDL-C reduction in order to achieve the lower targets recommended in recent guidelines,” Evan Stein, MD, PhD, founder, CEO, and chief scientific officer of LIB Therapeutics, said in the news release.¹ “Today’s FDA approval validates that mission and the focus of my medical career.”

Trial Program and LDL-C Lowering

The full LIBerate Program enrolled more than 2900 adults, including patients with established cardiovascular disease (CVD) and patients without CVD but with high or very high risk, including patients with heterozygous and homozygous FH. Lerodalcibep was administered once monthly for up to 52 weeks in placebo-controlled trials, with more than 2200 patients continuing into a 72-week open-label extension.² LIBerate-004 specifically included 478 patients with HeFH and compared lerodalcibep with placebo for 24 weeks.

Across the studies, LIB Therapeutics reported sustained LDL-C reductions of 60% or greater in patients with or at high risk for CVD and reductions of at least 50% in those with HeFH.¹ The therapy was generally well tolerated, with no treatment-related serious adverse events reported in the long-term extension studies, according to the company. The most commonly reported adverse reactions included nasopharyngitis, injection site reactions, and peripheral edema, with injection site reactions being the most frequent reason for treatment discontinuation.

Phase 3 Data in HeFH

Phase 3 safety and efficacy findings in adults with HeFH were published in 2023 in the European Heart Journal.³ In the randomized, double-blind trial, 478 adults with HeFH were assigned in a 2:1 ratio to receive monthly subcutaneous lerodalcibep 300 mg or placebo for 24 weeks. Participants had a mean age of 53 years, nearly 52% were female, and baseline LDL-C averaged 3.88 mmol/L (approximately 150 mg/dL), reflecting a population with substantial residual cholesterol burden despite treatment.

At week 24, patients on lerodalcibep saw their LDL-C reduce by an absolute 2.08 mmol/L compared with placebo, corresponding to a placebo-adjusted reduction of 58.6%. When averaged across weeks 22 and 24, LDL-C lowering was even greater, with an absolute reduction of 2.28 mmol/L and a relative reduction of 65.0% (P < .0001 for all primary endpoints). Nearly 70% of treated patients achieved both a 50% or greater LDL-C reduction and the European Society of Cardiology’s recommended LDL-C targets during the study period.

Beyond LDL-C, lerodalcibep was associated with a nearly 50% reduction in apolipoprotein B levels and a 24% reduction in lipoprotein(a). This effect is consistent with other PCSK9-directed therapies and is potentially relevant given lipoprotein(a)’s independent association with atherosclerotic cardiovascular disease risk in HeFH.

Positioning Within Lipid Management

Lerodalcibep-liga is described as a third-generation PCSK9 inhibitor and is formulated as a single small-volume injection with room-temperature stability of up to 3 months.¹ These features are intended to address barriers that have limited broader uptake of existing PCSK9 inhibitors, including storage requirements and administration burden. Dean J. Kereiakes, MD, chairman of The Christ Hospital Heart and Vascular Institute, noted in the release that the drug’s once-monthly dosing and at-home administration could make it a practical option for patients requiring lifelong cholesterol management.

“While oral PCSK9 inhibitors are in early development and appear promising, daily administration is necessary, and, as food significantly reduces absorption, patients are required to fast and not consume food for at least 30-min post-dose,” researchers wrote.³ “It also remains to be shown if tolerability and efficacy during longer-term treatment with oral PCSK9 inhibitors are sustained especially in patients on multiple medications with established ASCVD [atherosclerotic cardiovascular disease] or with multiple co-morbidities at very high risk for ASCVD.”

LIB Therapeutics said it plans to work with payers, clinicians, and patient advocacy groups to support access following launch.¹ The company has also submitted a marketing authorization application to the European Medicines Agency, with a regulatory decision anticipated in 2026.

References

1. U.S. Food and Drug Administration approves LIB Therapeutics’ Lerochol (lerodalcibep-liga) for adults with elevated LDL cholesterol. News release. LIB Therapeutics. December 15, 2025. Accessed December 15, 2025. https://libtherapeutics.com/news-and-events/us-food-and-drug-administration-approves-lib-therapeutics-lerochol-for-adults-with-elevated-ldl-cholesterol.html
2. Phase 3 LIBerate program. LIB Therapeutics. Accessed December 15, 2025. https://libtherapeutics.com/ph3-liberate
3. Raal F, Fourie N, Scott R, et al. Long-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trial. Eur Heart J. 2023;44(40):4272-4280. doi:10.1093/eurheartj/ehad596