Volanesorsen, sold under the brand name Waylivra, is a triglyceride-reducing drug. It is a second-generation 2'-''O''-methoxyethyl (2'-MOE) chimeric antisense therapeutic

oligonucleotide Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small bits of nucleic acids c ...

(ASO) that targets the

messenger RNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the p ...

for apolipoprotein C₃ (apo-CIII). The most common side effects include reduced platelet levels and reactions at the site of the injection such as pain, swelling, itching, or bruising. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Volanesorsen, is an 'antisense oligonucleotide,' a very short piece of synthetic RNA (a type of genetic material). It has been designed to block the production of a protein that slows down the breakdown of fats called apolipoprotein C-III. By blocking the production of this protein, the medicine reduces the level of triglycerides in the blood and, as a result, fat accumulation in the body, which is expected to reduce the risk of pancreatitis.

Medical uses

Familial chylomicronaemia syndrome (FCS) (also known as type I hyperlipoproteinaemia) is an inherited disease where people have abnormally high levels of some types of fat called triglycerides in their blood. The excess fat accumulates in organs such as the spleen and liver, which become abnormally enlarged. Fat accumulation can also cause repeated bouts of pancreatitis (inflammation of the pancreas) and xanthomas (formation of yellow fatty deposits just under the skin, generally around joints) Volanesorsen is indicated as an adjunct to diet in adults with genetically confirmed familial chylomicronemia syndrome (FCS) and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate.

History

It is in Phase III clinical trials for the treatment of hypertriglycidemia,

familial chylomicronemia syndrome Lipoprotein lipase deficiency is a genetic disorder in which a person has a defective gene for lipoprotein lipase, which leads to very high triglycerides, which in turn causes stomach pain and deposits of fat under the skin, and which can lead t ...

and

familial partial lipodystrophy Familial partial lipodystrophy, also known as Köbberling–Dunnigan syndrome, is a rare genetic metabolic condition characterized by the loss of subcutaneous fat. FPL also refers to a rare metabolic condition in which there is a loss of subcutane ...

. The drug was discovered and developed by

Ionis Pharmaceuticals Ionis Pharmaceuticals, Inc. is a biotechnology company based in Carlsbad, California, that specializes in discovering and developing RNA-targeted therapeutics. The company has 3 commercially approved medicines: Spinraza (Nusinersen), Tegsedi ( I ...

. Volanesorsen was designated an

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA) in February 2014, for phosphorothioate oligonucleotide targeted to apolipoprotein C-III for treatment of familial chylomicronaemia syndrome. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Volanesorsen was approved for medical use in the European Union in May 2019. Volanesorsen was effective in reducing triglycerides in the blood in a study of 67 participants with familial chylomicronemia syndrome (FCS). After three months, participants given volanesorsen had an average 77% reduction in the level of triglycerides compared with an average 18% increase in participants given placebo (a dummy treatment). All participants in the study were on a low-fat diet in addition to receiving volanesorsen or placebo.

Chemistry

The complete sequence of volanesorsen is: :

3'—A*— G*— mC*— T*— T*— dmC— dT— dT— dG— dT— dmC— dmC— dA— dG— dmC— T*— T*— T*— A*— T*—5'

:* = 2'-''O''-(2-methoxyethyl) :m = 5-methyl :d = 2'-deoxy

Names

Volanesorsen is the International nonproprietary name (INN).

References

External links

* {{Portal bar , Medicine Antisense RNA Hypolipidemic agents Therapeutic gene modulation Orphan drugs