Purpose of Review

To revise the clinical evidence supporting the use of volanesorsen as new lipid-lowering drug and to assess the efficacy and safety of volanesorsen (ISIS 304801) through a systematic review of the literature and a meta-analysis of the available phase 2 and phase 3 clinical studies.

Recent Findings

The meta-analysis of three clinical studies comprising 11 arms (N = l 156 subjects, with 95 in the active-treated arm and 61 in the control one) shows that volanesorsen significantly affects plasma levels of triglycerides (TG) [MD = − 67.90%, 95%CI = − 85.32, − 50.48, P < 0.001], high-density lipoprotein cholesterol (HDL-C) [MD = 40.06%, 95%CI: 32.79, 47.34, P < 0.001], very-low-density lipoprotein cholesterol (VLDL-C) [MD = − 72.90%, 95%CI = − 82.73, − 63.07, P < 0.001], apolipoprotein B (Apo B) [MD = 8%, 95%CI = 2.17, 13.84, P = 0.007], Apo B-48 [MD = − 64.63, 95%CI = − 105.37, − 23.88, P = 0.002], ApoCIII [MD = − 74.83%, 95%CI = − 85.93, − 63.73, P < 0.001], and VLDL ApoCIII [MD = − 83.69%, 95%CI = − 94.08, − 73.29, P < 0.001], without significant impact on LDL-C [MD = 47.01%, 95%CI = − 1.31, 95.33, P = 0.057] levels. Treatment with volanesorsen was associated with an higher risk of injection site reaction (OR = 32.89, 95%CI = 7.97,135,74, P < 0.001) and with an increased risk of upper respiratory tract infections (OR = 10.58, 95%CI = 1.23, 90.93, P < 0.05) when compared to placebo.

Summary

Volanesorsen has a relevant impact on plasma TG and related parameters without affecting LDL cholesterolemia and is associated with an acceptable safety profile.

中文翻译：

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Volanesorsen的功效和安全性（ISIS 304801）：来自2和3期临床试验的证据。

审查目的

修订有关支持将Volanesorsen用作降脂新药的临床证据，并通过系统地回顾文献和对可用的2期和3期临床进行荟萃分析，评估Volanesorsen的功效和安全性（ISIS 304801）学习。

最近的发现

对包括11个组（N  = 156个受试者，其中95个在积极治疗组，61个在对照组）中的三项临床研究的荟萃分析表明，福乐松显着影响甘油三酸酯（TG）的血浆水平[MD =-67.90 ％，95％CI = − 85.32，− 50.48，P  <0.001]，高密度脂蛋白胆固醇（HDL-C）[MD = 40.06％，95％CI：32.79，47.34，P  <0.001]，非常低密度脂蛋白胆固醇（VLDL-C）[MD = − 72.90％，95％CI = − 82.73，− 63.07，P <  0.001]，载脂蛋白B（Apo B）[MD = 8％，95％CI = 2.17，13.84，P  = 0.007]，Apo B-48 [MD = − 64.63，95％CI = − 105.37，− 23.88，P  = 0.002]，ApoCIII [MD = − 74.83％，95％CI = − 85.93，− 63.73，P <0.001]和VLDL ApoCIII [MD = − 83.69％，95％CI = − 94.08，− 73.29，P  <0.001]，而对LDL-C无明显影响[MD = 47.01％，95％CI = − 1.31，95.33 ，P  ＝ 0.057]水平。用Volanesorsen进行治疗与注射部位反应的风险较高（OR = 32.89，95％CI = 7.97,135,74，P  <0.001）和上呼吸道感染的风险较高（OR = 10.58，95％CI 与安慰剂相比= 1.23，90.93，P <0.05）。

概要

Volanesorsen在不影响LDL胆固醇血症的情况下对血浆TG和相关参数具有相关影响，并具有可接受的安全性。