Lerodalcibep’s FDA Approval For Hypercholesterolemia With Dean Kereiakes, MD

New insights suggest the recently FDA-approved lerodalcibep (Lerochol) may address the unmet needs of adults with hypercholesterolemia by improving accessibility, quality of life, and affordability.1

Recent discussion highlights the potential of the PCSK9 inhibitor to reduce low-density lipoprotein cholesterol (LDL-C) in this patient population, including those with heterozygous familial hypercholesterolemia (HeFH), further expanding the treatment landscape.1

“More options and more players in this space will mean better medicine for more patients, but it will also make these therapies more affordable,” said Dean Kereiakes, MD, chairman of The Christ Hospital Heart and Vascular Institute, in an interview with HCPLive. “I’ve had too many patients who couldn’t afford the best treatment, and that era is coming to an end.”

For patients currently taking statins, common side effects include severe muscle cramping after exertion. Kereiakes noted he has seen >100 patients experience these cramps, which result from statin-induced depletion of muscle energy stores combined with physical activity.2

PCSK9 inhibitors provide an effective and generally well-tolerated mechanism to reduce LDL-C, but widespread implementation has been limited by convenience and access barriers. Lerodalcibep, a novel, small protein-binding, third-generation PCSK9 inhibitor, was designed to bridge this therapeutic gap.1,3

The FDA approved lerodalcibep for use as an adjunct to diet and exercise to reduce LDL-C based on results from the LIBerate program, a series of 5 global, placebo-controlled phase 3 registration studies. In these trials, lerodalcibep was administered once monthly for 52 weeks, followed by a 72-week open-label extension.3

Overall, the LIBerate program enrolled > 2900 patients, including those with cardiovascular disease (CVD) and those without CVD but at very high or high risk. In the open-label extension, approximately 2400 patients continued treatment.3

In clinical trials, lerodalcibep produced sustained LDL-C reductions of ≥60% in patients with, or at very high or high risk of, cardiovascular disease, and ≥50% in those with HeFH, who typically have more severe LDL-C elevations.3

“That’s important, because some of the other medicines have more of a sawtooth effect where levels go down after the injection or infusion, then start to come back up before the next dose,” explained Kereiakes. “That’s less effective and provides less benefit than pushing LDL down and keeping it down. This has been a huge unmet need, and I think the success of this class of drugs reflects that need.”

Differing from other PCSK9 inhibitors, lerodalcibep can be self-administered once monthly, offering a convenient option for patients requiring lifelong cholesterol management. The drug can also be maintained at room temperature for up to three months.1,3

The most frequent adverse reaction leading to treatment discontinuation in trials for primary hypercholesterolemia was injection-site reactions, occurring in 1% of lerodalcibep-treated patients compared with 0% of placebo-treated patients.3

“I’ve actually told patients that I think PCKS9 inhibitors are the greatest thing to happen in cardiovascular medicine in over a decade. They’ve allowed us to stabilize high-risk patients who would have otherwise had more events,” concluded Kereiakes, “And I think we’ll have a rapid ramp-up of these therapies because it’s got advantages over those that are currently available.”

Editor’s Note: Kereiakes reports relevant disclosures with Ablative Solutions Inc., Shockwave, CeleCor, and others.

References

1. National Lipid Association. U.S. Food and Drug Administration Approves LIB Therapeutics’ LEROCHOLTM (lerodalcibep-liga) for Adults with Elevated LDL Cholesterol | National Lipid Association Online. Lipid.org. Published 2025. Accessed December 16, 2025. https://www.lipid.org/nla/us-food-and-drug-administration-approves-lib-therapeutics%E2%80%99-lerochol%E2%84%A2-lerodalcibep-liga-adults

2. Harvard Health Publishing. Managing statin muscle pain - Harvard Health. Harvard Health. Published August 9, 2019. https://www.health.harvard.edu/pain/managing-statin-muscle-pain

3. LIB Therapeutics. U.S. Food and Drug Administration Approves LIB Therapeutics’ LEROCHOL™ (lerodalcibep-liga) for Adults with Elevated LDL Cholesterol. News & Events. Libtherapeutics.com. Published 2025. Accessed December 16, 2025. https://libtherapeutics.com/news-and-events/us-food-and-drug-administration-approves-lib-therapeutics-lerochol-for-adults-with-elevated-ldl-cholesterol.html