MK-0616, a novel oral macrocyclic peptide inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), represents a significant advancement in the treatment of hypercholesterolemia. Unlike current PCSK9 inhibitors, which are injectable monoclonal antibodies and siRNA molecules, MK-0616 offers a patient-friendly alternative. The development of MK-0616 involved innovative synthetic chemistry and in vitro mRNA display technology. This cutting-edge approach led to the creation of an orally administered peptide with the ability to cover a larger portion of PCSK9 compared to smaller, linear peptides. Phase 1 and 2b clinical trials have demonstrated MK-0616's safety, efficacy, and pharmacokinetics. These trials indicate the drug's dose-dependent systemic absorption and long half-life. Notably, MK-0616 has exhibited comparable low-density lipoprotein cholesterol-lowering effects to currently available PCSK9 inhibitors, all while maintaining good tolerability in diverse patient populations, including those concurrently on statin therapy. As MK-0616 advances to Phase 3 trials, its lipid-lowering potential for heterozygous familial hypercholesterolemia and its impact on reducing the time to adverse cardiac events will be evaluated in a broad and diverse population, including underrepresented groups. The results achieved so far are promising for individuals with hypercholesterolemia, as they offer a potential solution for effectively lowering low-density lipoprotein cholesterol in patients on statin therapy and mitigating the risk of cardiovascular events. Ongoing research and monitoring will be critical to establish its long-term safety and efficacy, but MK-0616 may emerge as a valuable addition to the array of lipid-lowering therapies available to patients.

中文翻译：

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新型口服 PCSK9 抑制剂：“MK-0616”。

MK-0616 是一种新型口服大环肽前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9) 抑制剂，代表了高胆固醇血症治疗的重大进展。与目前的 PCSK9 抑制剂（可注射的单克隆抗体和 siRNA 分子）不同，MK-0616 提供了一种对患者友好的替代方案。MK-0616的开发涉及创新的合成化学和体外mRNA展示技术。这种尖端方法催生了一种口服肽，与较小的线性肽相比，它能够覆盖更大的 PCSK9 部分。1期和2b期临床试验已经证明了MK-0616的安全性、有效性和药代动力学。这些试验表明该药物具有剂量依赖性全身吸收和长半衰期。值得注意的是，MK-0616 表现出与目前可用的 PCSK9 抑制剂相当的低密度脂蛋白胆固醇降低作用，同时在不同患者群体（包括同时接受他汀类药物治疗的患者）中保持良好的耐受性。随着 MK-0616 进入 3 期试验，其对杂合子家族性高胆固醇血症的降脂潜力及其对缩短不良心脏事件时间的影响将在广泛和多样化的人群中进行评估，包括代表性不足的群体。迄今为止取得的结果对于高胆固醇血症患者来说是有希望的，因为它们为有效降低接受他汀类药物治疗的患者的低密度脂蛋白胆固醇并减轻心血管事件的风险提供了潜在的解决方案。持续的研究和监测对于确定其长期安全性和有效性至关重要，但 MK-0616 可能会成为患者可用的一系列降脂疗法的有价值的补充。