Apolipoprotein C-III (apoC-III) is a protein found in the bloodstream. Volanesorsen (formerly ISIS-APOCIIIRx) is designed to reduce the amount of apoC-III in the bloodstream. Reducing the amount of apoC-III in the blood may help people lower the amount of triglycerides in the bloodstream, a significant risk factor for pancreatitis.
In a Phase 2 proof-of-concept study, three FCS patients (patients with Familial Chylomicronemia Syndrome, also known as Type 1 Hyperlipoproteinemia or Lipoprotein Lipase (LPL) deficiency) were treated for 13 weeks with volanesorsen (formerly ISIS-APOCIIIRx). In this study, clinicians observed substantial decreases in triglycerides between 56 to 86% which equated to absolute changes of 790 to 1796 mg/dL.1 The APPROACH Trial is designed to obtain longer-term, placebo-controlled data on triglyceride lowering with volanesorsen (formerly ISIS APOCIIIRx) in a larger group of FCS patients. The data will be part of the approval application of the drug.
Isis has also evaluated volanesorsen (formerly ISIS-APOCIIIRx) in a placebo controlled Phase 2 program of 100 patients with hypertriglyceridemia. Clinically observed patients treated with volanesorsen (formerly ISIS-APOCIIIRx) experienced substantial lowering of triglycerides (reductions of up to 71%) and apoC-III (reductions of up to 88%). Volanesorsen (formerly ISIS-APOCIIIRx) was generally well tolerated. There was a low incidence of mild injection site reactions and no clinically meaningful changes in laboratory values.
Volanesorsen (formerly ISIS-APOCIIIRx) is a novel, first-in-class investigational drug developed with the aim of reducing the blood levels of apoC-III in patients with high triglycerides. ApoC-III is a protein that is attached to triglyceride containing particles in the blood. It is thought that apoC-III mostly likely acts like a braking system on the body’s process for removing triglycerides from the bloodstream. High levels of apoC-III slow down the metabolism and/or removal of triglycerides from the bloodstream, which can lead to a condition called hypertriglyceridemia.
Volanesorsen (formerly ISIS-APOCIIIRx) is expected to work by directly targeting and reducing apoC-III production at the level of the genetic machinery inside the liver cells. When apoC-III production is decreased in this manner, the amount of apoC-III protein in the bloodstream is reduced, and this could help reduce the levels of triglycerides in the bloodstream. Reducing triglycerides in the bloodstream may reduce the overall risk of having an attack of acute pancreatitis. In a short-term clinical trial in patients with hypertriglyceridemia, clinicians observed that patients treated with volanesorsen (formerly ISIS-APOCIIIRx) had substantially reduced triglyceride levels in the bloodstream and tolerated the drug well. Evidence regarding the efficacy of volanesorsen (formerly ISIS-APOCIIIRx) in reducing attacks of acute pancreatitis is not yet available.
Volanesorsen (formerly ISIS-APOCIIIRx) is not a commercial product; it is an investigational compound that is currently being evaluated in clinical trials in patients with varying degrees of hypertriglyceridemia, where the patients can be closely monitored in a controlled setting. Until the safety and efficacy of this investigational compound can be established, access to the compound is limited to those patients participating in the clinical trials. This helps ensure that the compound will be on an efficient path to completing the testing necessary for it to become available to all who can benefit.
Volanesorsen (formerly ISIS-APOCIIIRx) was developed by Isis Pharmaceuticals, and is now being progressed by Akcea Therapeutics, a wholly owned subsidiary of Isis Pharmaceuticals.
1Gaudet D, Brisson D, Tremblay K, Alexander VJ, Singleton W, Hughes SG, Geary RS, Baker BF, Graham MJ, Crooke RM, Witztum JL. (2014) Targeting APOC3 in the familial chylomicronemia syndrome. The New England Journal of Medicine 371, 2200-2206.
Isis Pharmaceuticals is the industry leader in the development of a new drug class called antisense oligonucleotides. These drugs are the most advanced form of what are called “RNA therapeutics” and exert their effect by a type of therapy called ‘gene silencing.’ They are designed to shut down protein production by the target gene, and thus silence its effects, rather than repairing a faulty gene or by treating the protein after it is made. Isis Pharmaceuticals is the only company to have an RNA therapeutics-based drug approved for treating patients.
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