Английская Википедия:Glecaprevir/pibrentasvir

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Glecaprevir/pibrentasvir (G/P), sold under the brand names Mavyret and Maviret, is a fixed-dose combination medication used to treat hepatitis C.[1][2] It contains glecaprevir and pibrentasvir.[2][3] It works against all six types of hepatitis C.[1] At twelve weeks following treatment between 81% and 100% of people have no evidence of hepatitis C.[4] It is taken once a day by mouth with food.[1][2]

The most common side effects are headache, diarrhea, and tiredness.[4][5] In those with a history of hepatitis B, reactivation may occur.[5] It is not recommended in people with moderate to severe liver disease.[4] Glecaprevir works by blocking the protein NS3/4A protease, while pibrentasvir works by blocking NS5A.[1]

The combination was approved for medical use in the United States and Europe in 2017.[3][1] It is on the World Health Organization's List of Essential Medicines.[6]

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).[4][2] 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.[2] The duration of treatment was shortened from 12 weeks to eight weeks for many people in 2019.[4]

In the European Union, it is used to treat adults and adolescents aged 12 years and older with chronic (long-term) hepatitis C.[1]

Side effects

The only known side effects of G/P are hepatitis B reactivation, and more commonly headache, nausea, tiredness, and diarrhea.[7]

Mechanism of action

Glecaprevir inhibits NS3/4A, a serine protease, and pibrentasvir inhibits NS5A, a zinc-binding hydrophilic phosphoprotein. Both of these proteins are essential in hepatitis C viral RNA replication, which can no longer take place upon inhibition of these proteins.[7]

History

The development of G/P as a combination treatment was done by AbbVie and is in accordance with good manufacturing practice (GMP) standards, per the FDA.[7]

Initial identification of glecaprevir was done in a joint effort by AbbVie and Enanta Pharmaceuticals.[8] Enanta had a Collaborative Development and License Agreement with AbbVie for the identification and development of paritaprevir and glecaprevir, two HCV NS3 and NS3/4A protease inhibitors, that lasted from October 2016 to June 2017. In this agreement, Enanta received a total of Шаблон:US$ in the form of license payments, proceeds from a sale of preferred stock, research funding payments, milestone payments, and royalties.[9]

The identification and development of pibrentasvir was done by AbbVie.[10]

Research

During clinical trials, G/P was shown to be effective at clearing all six genotypes 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.[7]

References

Шаблон:Reflist

External links

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