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Efficacy and Safety of Volanesorsen (ISIS 304801): the Evidence from Phase 2 and 3 Clinical Trials

  • Evidence-Based Medicine, Clinical Trials and Their Interpretations (L. Roever , Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

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.

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Funding

The present paper was written independently; no company or institution supported it financially. No professional writer was involved in the preparation of this meta-analysis.

Author information

Author notes

  1. Federica Fogacci and Giuseppe Danilo Norata contributed equally to this work.

Authors and Affiliations

  1. Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, Bologna, Italy

    Federica Fogacci & Arrigo F. G. Cicero

  2. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy

    Giuseppe Danilo Norata

  3. The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Peter P. Toth

  4. Preventive Cardiology, CGH Medical Center, Sterling, IL, USA

    Peter P. Toth

  5. Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy

    Marcello Arca

  6. Medical and Surgical Sciences Department, Sant’Orsola-Malpighi University Hospital, Via Albertoni, 15, 40138, Bologna, Italy

    Arrigo F. G. Cicero

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Correspondence to Arrigo F. G. Cicero.

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Conflict of Interest

Federica Fogacci has served as a consultant to Mylan; Danilo Giuseppe Norata reports grants from Pfizer, Amgen, Alnylam, and Sanofi; Peter P. Toth reports personal fees from Amgen, Amarin, Kowa, Novo Nordisk, Resverlogix, Regeneron, and Sanofi; Marcello Arca reports grants from Akcea/Ionis; Arrigo F.G. Cicero has given talks, furnished scientific consultancies, and/or participated in trials sponsored by Amgen, Angelini, Menarini, and Mylan.

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Fogacci, F., Norata, G.D., Toth, P.P. et al. Efficacy and Safety of Volanesorsen (ISIS 304801): the Evidence from Phase 2 and 3 Clinical Trials. Curr Atheroscler Rep 22, 18 (2020). https://doi.org/10.1007/s11883-020-00836-w

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