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Ongericimab (JS002) is a novel PCSK9 monoclonal antibody that exhibits a long\u2010acting LDL\u2010C lowering effect by exclusively inhibiting PCSK9 in pre\u2010clinical studies. Two randomized, double\u2010blind, placebo\u2010controlled trials were conducted to evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetic, and pharmacodynamic profiles of ongericimab in healthy subjects and patients with hypercholesterolemia. Eighty\u2010four healthy subjects in the phase Ia study received a single dose of placebo or ongericimab (15\u2013450\u2009mg). Ninety patients with hypercholesterolemia in the phase Ib\/II study received placebo or ongericimab 150\u2009mg Q2W, 300\u2009mg Q4W, or 450\u2009mg Q4W for 12\u2009weeks. Ongericimab exhibited non\u2010linear kinetics. The apparent clearance decreased as the dosage increased, with terminal elimination half\u2010life (t<jats:sub>1\/2<\/jats:sub>) values of 4.5\u20136.5\u2009days. Overall, ongericimab was well tolerated in both studies. A single dose of ongericimab reduced LDL\u2010C levels by 30%\u201373% in healthy subjects, and repeated doses of ongericimab reduced LDL\u2010C levels by 67%\u201380% in patients with hypercholesterolemia. At the end of the dosing interval in the phase Ib\/II study, over 70% of patients' LDL\u2010C levels decreased by more than 50% from baseline. The results showed that ongericimab had a significant long\u2010acting LDL\u2010C lowering effect with good safety and potential for clinical application.<\/jats:p>","DOI":"10.1111\/cts.70061","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T12:59:35Z","timestamp":1730811575000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinical pharmacokinetics and pharmacodynamics of ongericimab: A potential long\u2010acting PCSK9 monoclonal antibody in healthy subjects and patients with hypercholesterolemia: Randomized, double\u2010blind, placebo\u2010controlled phase Ia and Ib\/II studies"],"prefix":"10.1111","volume":"17","author":[{"given":"Juanjuan","family":"Jiang","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Clinical Research for Cardiovascular Medications, National Clinical Research Center of Cardiovascular Diseases Fuwai Hospital, National Center for 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