BACKGROUND Persistent chylomicronemia is a genetic recessive disorder that is classically caused by familial chylomicronemia syndrome (FCS), but it also has multifactorial causes. The disorder is associated with the risk of recurrent acute pancreatitis. Plozasiran is a small interfering RNA that reduces hepatic production of apolipoprotein C-III and circulating triglycerides. METHODS In a phase 3 trial, we randomly assigned 75 patients with persistent chylomicronemia (with or without a genetic diagnosis) to receive subcutaneous plozasiran (25 mg or 50 mg) or placebo every 3 months for 12 months. The primary end point was the median percent change from baseline in the fasting triglyceride level at 10 months. Key secondary end points were the percent change in the fasting triglyceride level from baseline to the mean of values at 10 months and 12 months, changes in the fasting apolipoprotein C-III level from baseline to 10 months and 12 months, and the incidence of acute pancreatitis. RESULTS At baseline, the median triglyceride level was 2044 mg per deciliter. At 10 months, the median change from baseline in the fasting triglyceride level (the primary end point) was -80% in the 25-mg plozasiran group, -78% in the 50-mg plozasiran group, and -17% in the placebo group (P<0.001). The key secondary end points showed better results in the plozasiran groups than in the placebo group, including the incidence of acute pancreatitis (odds ratio, 0.17; 95% confidence interval, 0.03 to 0.94; P = 0.03). The risk of adverse events was similar across groups; the most common adverse events were abdominal pain, nasopharyngitis, headache, and nausea. Severe and serious adverse events were less common with plozasiran than with placebo. Hyperglycemia with plozasiran occurred in some patients with prediabetes or diabetes at baseline. CONCLUSIONS Patients with persistent chylomicronemia who received plozasiran had significantly lower triglyceride levels and a lower incidence of pancreatitis than those who received placebo. (Funded by Arrowhead Pharmaceuticals; PALISADE ClinicalTrials.gov number, NCT05089084.).

中文翻译：

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Plozasiran 用于管理持续性乳糜微粒血症和胰腺炎风险。


背景 持续性乳糜微粒血症是一种遗传隐性遗传病，通常由家族性乳糜微粒血症综合征 （FCS） 引起，但它也有多因素原因。该疾病与复发性急性胰腺炎的风险有关。Plozasiran 是一种小干扰 RNA，可减少肝脏载脂蛋白 C-III 和循环甘油三酯的产生。方法 在一项 3 期试验中，我们随机分配了 75 名持续性乳糜微粒血症患者 （有或没有基因诊断） 接受皮下注射 plozasiran （25 mg 或 50 mg） 或安慰剂，每 3 个月一次，持续 12 个月。主要终点是 10 个月时空腹甘油三酯水平相对于基线的中位百分比变化。关键的次要终点是空腹甘油三酯水平从基线到 10 个月和 12 个月值的平均值的百分比变化，空腹载脂蛋白 C-III 水平从基线到 10 个月和 12 个月的变化，以及急性胰腺炎的发病率。结果 基线时，甘油三酯水平中位为 2044 毫克/分升。10 个月时，空腹甘油三酯水平 （主要终点） 相对于基线的中位变化在 25 mg plozasiran 组中为 -80%，在 50 mg plozasiran 组中为 -78%，在安慰剂组中为 -17% （P<0.001）。关键次要终点显示 plozasiran 组的结果优于安慰剂组，包括急性胰腺炎的发生率（比值比，0.17;95% 置信区间，0.03 至 0.94;P = 0.03）。各组不良事件的风险相似;最常见的不良事件是腹痛、鼻咽炎、头痛和恶心。与安慰剂相比，plozasiran 组的严重和严重不良事件较少见。 plozasiran 的高血糖发生在一些糖尿病前期或基线糖尿病患者中。结论 与接受安慰剂的患者相比，接受 plozasiran 治疗的持续性乳糜微粒血症患者的甘油三酯水平显著降低，胰腺炎发生率更低。（由 Arrowhead Pharmaceuticals 资助;PALISADE ClinicalTrials.gov 编号，NCT05089084.）。