Department of Medicine, University of California San Diego, Room 1081, 9500 Gilman Drive, La Jolla, CA 92093 USA (Drs Joseph L. Witztum; Sotirios Tsimikas).
Lipidology Unit, Community Genomic Medicine Center, Department of Medicine, Université de Montréal and ECOGENE-21, 930 Jacques-Cartier Est, Chicoutimi, Quebec G7H 7K9, Canada (Dr Daniel Gaudet).
J Clin Lipidol. 2023 May-Jun;17(3):342-355. doi: 10.1016/j.jacl.2023.03.007. Epub 2023 Mar 22.
Familial chylomicronemia syndrome (FCS) is a rare, autosomal recessive genetic disorder characterized by a marked increase in plasma triglyceride (TG) levels and recurrent episodes of pancreatitis. The response to conventional TG-lowering therapies is suboptimal. Volanesorsen, an antisense oligonucleotide that targets hepatic apoC-III mRNA, has been shown to significantly reduce TGs in patients with FCS.
To further evaluate the safety and efficacy of extended treatment with volanesorsen in patients with FCS.
This phase 3 open-label extension study evaluated the efficacy and safety of extended treatment with volanesorsen in three groups of patients with FCS: Those who had previously received volanesorsen or placebo in the APPROACH and COMPASS studies, and treatment-naive patients not participating in either study. Key endpoints included change in fasting TG and other lipid measurements, and safety over 52 weeks.
Volanesorsen treatment resulted in sustained reductions in plasma TG levels in previously treated patients from the APPROACH and COMPASS studies. Volanesorsen-treated patients from the three populations studied had mean decreases in fasting plasma TGs from index study baseline to months 3, 6, 12 and 24 as follows: decreases of 48%, 55%, 50%, and 50%, respectively (APPROACH); decreases of 65%, 43%, 42%, and 66%, respectively (COMPASS); and decreases of 60%, 51%, 47%, and 46%, respectively (treatment-naive). Common adverse events were injection site reactions and platelet count decrease, consistent with previous studies.
Extended open-label treatment with volanesorsen in patients with FCS resulted in sustained reductions of plasma TG levels and safety consistent with the index studies.
家族性乳糜微粒血症综合征（FCS）是一种罕见的常染色体隐性遗传疾病，其特征是血浆甘油三酯（TG）水平显著升高，反复发作胰腺炎。常规的 TG 降低治疗效果不佳。Volanesorsen 是一种针对肝载脂蛋白 C-III mRNA 的反义寡核苷酸，已被证明可显著降低 FCS 患者的 TG。
进一步评估 FCS 患者延长使用 Volanesorsen 的安全性和疗效。
这项 3 期开放标签扩展研究评估了 FCS 患者延长使用 Volanesorsen 的疗效和安全性。三个患者组接受了治疗：既往接受过 Volanesorsen 或安慰剂的 APPROACH 和 COMPASS 研究患者，以及未参与任何研究的治疗初治患者。主要终点包括空腹 TG 和其他脂质测量的变化，以及 52 周的安全性。
Volanesorsen 治疗使既往接受 APPROACH 和 COMPASS 研究治疗的患者的血浆 TG 水平持续降低。来自三个研究人群的接受 Volanesorsen 治疗的患者，从基线到第 3、6、12 和 24 个月的空腹血浆 TG 分别下降如下：分别下降 48%、55%、50%和 50%（APPROACH）；分别下降 65%、43%、42%和 66%（COMPASS）；分别下降 60%、51%、47%和 46%（治疗初治）。常见的不良反应是注射部位反应和血小板计数下降，与既往研究一致。
FCS 患者延长开放标签使用 Volanesorsen 治疗可持续降低血浆 TG 水平，安全性与基准研究一致。
