Glecaprevir/pibrentasvir (G/P), sold under the brand names Mavyret and Maviret, is a

fixed-dose combination A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC prod ...

medication used to treat

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...

. It contains

glecaprevir Glecaprevir (INN,) is a hepatitis C virus (HCV) nonstructural (NS) protein 3/ 4A protease inhibitor that was identified jointly by AbbVie and Enanta Pharmaceuticals. It is being developed as a treatment of chronic hepatitis C infection in co-fo ...

and

pibrentasvir Pibrentasvir is an NS5A inhibitor antiviral agent. In the United States and Europe, it is approved for use with glecaprevir as the combination drug glecaprevir/pibrentasvir (trade name ''Mavyret'' in the US and ''Maviret'' in the EU) for the tr ...

. It works against all six types of hepatitis C. At twelve weeks following treatment between 81% and 100% of people have no evidence of hepatitis C. It is taken once a day by mouth with food. The most common side effects are headache, diarrhea, and tiredness. In those with a history of

hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...

reactivation may occur. It is not recommended in people with moderate to severe liver disease. Glecaprevir works by blocking the protein NS3/ 4A protease, while pibrentasvir works by blocking

NS5A Nonstructural protein 5A (NS5A) is a zinc-binding and proline-rich hydrophilic phosphoprotein that plays a key role in Hepatitis C virus RNA replication. It appears to be a dimeric form without ''trans''-membrane helices. Structure NS5A is deriv ...

. The combination was approved for medical use in the United States and Europe in 2017. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

Medical uses

In the United States, G/P is used to treat adults and children aged 12 years and older or weighing at least 99 pounds with chronic hepatitis C virus (HCV) genotypes 1–6 and both without cirrhosis and with compensated cirrhosis who have not been previously treated for HCV (treatment-naïve). It is also used to treat adults and children aged 12 years and older or weighing at least 99 pounds with chronic HCV genotype 1 infection who have previously been treated with a NS5A inhibitor or a NS3/4A inhibitor but not both. The duration of treatment was shortened from 12 weeks to eight weeks for many people in 2019. In the European Union, it is used to treat adults and adolescents aged 12 years and older with chronic (long-term) hepatitis C.

Side effects

The only known

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of G/P are

reactivation, and more commonly headache, nausea, tiredness, and diarrhea.

Mechanism of action

Glecaprevir inhibits NS3/ 4A, a

serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. ...

, and pibrentasvir inhibits

, a zinc-binding hydrophilic

phosphoprotein A phosphoprotein is a protein that is posttranslationally modified by the attachment of either a single phosphate group, or a complex molecule such as 5'-phospho-DNA, through a phosphate group. The target amino acid is most often serine, threonin ...

. Both of these proteins are essential in hepatitis C viral RNA replication, which can no longer take place upon inhibition of these proteins.

History

The development of G/P as a combination treatment was done by

AbbVie AbbVie is an American publicly traded biopharmaceutical company founded in 2013. It originated as a spin-off of Abbott Laboratories. History On October 19, 2011, Abbott Laboratories announced its plan to separate into two publicly traded compan ...

and is in accordance with

good manufacturing practice Current good manufacturing practices (cGMP) are those conforming to the guidelines recommended by relevant agencies. Those agencies control the authorization and licensing of the manufacture and sale of food and beverages, cosmetics, pharmaceutica ...

(GMP) standards, per the FDA. Initial identification of glecaprevir was done in a joint effort by AbbVie and Enanta Pharmaceuticals. Enanta had a Collaborative Development and License Agreement with AbbVie for the identification and development of

paritaprevir Paritaprevir (previously known as ABT-450) is an acylsulfonamide inhibitor of the NS3- 4A serine protease manufactured by Abbott Laboratories that shows promising results as a treatment of hepatitis C. When given in combination with ritonavir an ...

and glecaprevir, two HCV NS3 and NS3/4A

protease inhibitors Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. Some of the most well known are antiviral drugs widely used to treat HIV/AIDS and hepatitis C. These protease inhibitors prevent viral replicat ...

, that lasted from October 2016 to June 2017. In this agreement, Enanta received a total of in the form of license payments, proceeds from a sale of

preferred stock Preferred stock (also called preferred shares, preference shares, or simply preferreds) is a component of share capital that may have any combination of features not possessed by common stock, including properties of both an equity and a debt ins ...

, research funding payments, milestone payments, and

royalties A royalty payment is a payment made by one party to another that owns a particular asset, for the right to ongoing use of that asset. Royalties are typically agreed upon as a percentage of gross or net revenues derived from the use of an asset o ...

. The identification and development of pibrentasvir was done by AbbVie.

Research

During clinical trials, G/P was shown to be effective at clearing all six

genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...

s of HCV from the blood. Over the course of eight studies involving greater than 2,300 patients with hepatitis C, 99% of non-cirrhotic patients with genotype 1 were negative for HCV after the eight-week treatment regimen. Of cirrhotic patients from the same group, 97% tested negative for HCV on a 12-week treatment regimen and the results were reportedly similar for the treatment of genotypes 2 and 4–6, whereas 95% of patients with genotype 3 HCV tested negative for the virus after treatment.

References

External links

* {{DEFAULTSORT:Glecaprevir Pibrentasvir Combination drugs NS3/4A protease inhibitors NS5A inhibitors AbbVie brands World Health Organization essential medicines Wikipedia medicine articles ready to translate