Novel PCSK9 Inhibitor Recaticimab Lowers LDL-C in Adult Heterozygous Familial Hypercholesterolemia

Recaticimab, a novel, humanized, antiproprotein convertase subtilisin/kexin type 9 (PCSK9) antibody, significantly lowered low-density lipoprotein cholesterol (LDL-C) levels compared with placebo in adults with heterozygous familial hypercholesterolemia (HeFH), according to results from the multicenter, randomized, double-blind, placebo-controlled phase 3 REMAIN-3 trial (NCT04844125) published by investigators in Cardiovascular Research.^1,2

PCSK9 molecules are key regulators of cholesterol. | Image Credit: © Four888 - stock.adobe.com

Why Novel PCSK9 Inhibitors Are Sorely Needed

Patients with HeFH, an inherited genetic disorder, face seriously heightened plasma concentrations of LDL-C from birth. HeFH complicates the ability of the liver to metabolize particles carrying LDL-C through the bloodstream. The National Institutes of Health note that individuals with HeFH often present with LDL-C levels 2 to 3 times higher than normal. Because of these dangerously high LDL-C levels, individuals with HeFH are at increased risk for cardiovascular events—and because it is a genetic condition, lifestyle changes alone can’t manage patients’ LDL-C levels.³

Medications, including statins and PCSK9 inhibitors, therefore play an outsized role in this patient population. PCSK9, produced by the liver, helps regulate LDL receptors. By inhibiting PCSK9 proteins, these medications allow for more LDL receptors to work properly and more effectively break down and remove LDL-C. Adherence is a major concern with typical lipid-lowering therapies like statins, which often require daily use; however, PCSK9 inhibitors differ in that they are injected by a health care professional every 3 months, which could allow for more stringent adherence and more effective LDL-C lowering.^4,5

Novel PCSK9 options are sorely needed given the limited number of these medications currently approved by the FDA for use to lower LDL-C. Accordingly, investigators initiated the REMAIN-3 trial to evaluate the safety and efficacy of recaticimab, a novel monoclonal antibody that could allow for less-frequent dosing, even compared with standard PCSK9 inhibitors. Previously, in the phase 3 REMAIN-2 trial (NCT04885218), recaticimab as an add-on to stable statin therapy—in doses of either 150 mg, 300 mg, or 450 mg—significantly decreased LDL-C levels with a dosing interval of every 12 weeks, showing its potential for effective LDL-C regulation.^1,6

Recaticimab Could Transform Treatment Paradigm of HeFH

In REMAIN-3, recaticimab was set to undergo further evaluation featuring the 150-mg dose. Taking place across 25 sites in China, individuals enrolled had HeFH, were on stable lipid-lowering therapy for at least 28 days, featured fasting LDL-C of 2.6 mmol/L or more—or 1.8 mmol/L or more for those with a history of cardiovascular disease—and had fasting triglyceride levels of 5.6 mmol/L or less. In total, 143 patients were randomly assigned 2:1 to receive a 150-mg dose of subcutaneous recaticimab (n = 95) or a matching placebo (n = 48) every 4 weeks for 12 weeks. The authors primarily sought to evaluate the percentage change in LDL-C from baseline to week 12.¹

Mean percentage change in LDL-C from baseline was –54.4% (95% CI, –57.9% to –50.8%) in the recaticimab group and –4.5% (95% CI, –9.4% to 0.3%) in the placebo group at week 12, with a measured treatment difference of –49.8% (95% CI, –55.8% to –43.0%; P < .0001). Critically, recaticimab was more effective than placebo at improving other lipid variables, such as non–high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein A, according to the investigators.¹

Regarding safety, there were comparable rates of treatment-related adverse events (TRAEs) between either group (27.4% with recaticimab vs 25.0% with placebo). Common TRAEs that occurred more frequently with recaticimab than placebo were injection site reaction (8.4% vs 0%) and increased blood creatine phosphokinase (5.3% vs 2.1%). With comparable safety profiles, recaticimab presents as both a safe and effective option to lower LDL-C that would not compromise any other facets of a person’s health. Aside from monitoring these safety profiles, pharmacists could play an integral role in administration and follow-up.¹

“Recaticimab significantly lowered the LDL-C level compared with placebo, with an acceptable safety profile, providing a new effective treatment option for patients with inadequately controlled HeFH,” the REMAIN-3 authors concluded.¹

REFERENCES

1. Li L, Zhou Y, Deng C, et al. Recaticimab in adult heterozygous familial hypercholesterolemia (REMAIN-3): A multicentre, randomised, double-blind, placebo-controlled phase 3 study. Cardio Research. 2025:cvaf155. doi: 10.1093/cvr/cvaf155

2. SHR - 1209 Treatment Efficacy and Safety of the Patients With Hypercholesterolemia III Period Clinical Research. ClinicalTrials.gov Identifier: NCT04844125. Last Updated April 25, 2023. Accessed September 10, 2025. https://www.clinicaltrials.gov/study/NCT04844125

3. Brumit ML. What is heterozygous familial hypercholesterolemia? Family Heart Foundation. Published December 26, 2014. Accessed September 10, 2025. https://familyheart.org/heterozygous-familial-hypercholesterolemia

4. Halpern L. With Proper Adherence to Cholesterol-Lowering Drugs, Thousands of Cardiovascular Events Could Be Avoided. Pharmacy Times. Published July 10, 2025. Accessed September 10, 2025. https://www.pharmacytimes.com/view/with-proper-adherence-to-cholesterol-lowering-drugs-thousands-of-cardiovascular-events-could-be-avoided

5. Cleveland Clinic. PCSK9 inhibitors. Last Updated February 17, 2022. Accessed September 10, 2025. https://my.clevelandclinic.org/health/drugs/22550-pcsk9-inhibitors

6. Sun Y, Lv Q, Guo Y, et al. Recaticimab as Add-On Therapy to Statins for Nonfamilial Hypercholesterolemia: The Randomized, Phase 3 REMAIN-2 Trial. J Am Coll Cardiol. 2024;84(20):2037-2047. doi:10.1016/j.jacc.2024.09.012