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Glecaprevir/pibrentasvir

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Glecaprevir/pibrentasvir
Combination of
GlecaprevirNS3/NS4A inhibitor
PibrentasvirNS5A inhibitor
Clinical data
Trade namesMavyret, Maviret, others
AHFS/Drugs.comMonograph
MedlinePlusa617039
License data
Pregnancy
category
Routes of
administration		By mouth (tablets)
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)[2]
  • US: ℞-only
  • EU: Rx-only
  • In general: ℞ (Prescription only)
Identifiers
KEGG

Glecaprevir/pibrentasvir (G/P), sold under the brand names Mavyret and Maviret, is a fixed-dose combination medication used to treat hepatitis C.[3][4] It contains glecaprevir and pibrentasvir.[4][5] It works against all six types of hepatitis C.[3] At twelve weeks following treatment between 81% and 100% of people have no evidence of hepatitis C.[6] It is taken once a day by mouth with food.[3][4]

The most common side effects are headache, diarrhea, and tiredness.[6][7] In those with a history of hepatitis B reactivation may occur.[7] It is not recommended in people with moderate to severe liver disease.[6] Glecaprevir works by blocking the protein NS3/4A protease, while pibrentasvir works by blocking NS5A.[3]

The combination was approved for medical use in the United States and Europe in 2017.[5][3] It is on the World Health Organization's List of Essential Medicines.[8]

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).[6][4] 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.[4] The duration of treatment was shortened from 12 weeks to eight weeks for many people in 2019.[6]

In the European Union, it is used to treat adults and adolescents aged 12 years and older with chronic (long-term) hepatitis C.[3]

Side effects

The only known side effects of G/P are hepatitis B reactivation, and more commonly headache, nausea, tiredness, and diarrhea.[9]

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.[9]

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.[9]

Initial identification of glecaprevir was done in a joint effort by AbbVie and Enanta Pharmaceuticals.[10] 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 US$427,000 in the form of license payments, proceeds from a sale of preferred stock, research funding payments, milestone payments, and royalties.[11]

The identification and development of pibrentasvir was done by AbbVie.[12]

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.[9]

References

  1. ^ "Glecaprevir / pibrentasvir (Mavyret) Use During Pregnancy". Drugs.com. 10 October 2019. Retrieved 30 March 2020.
  2. ^ "Maviret 100 mg/40 mg Film-coated Tablets - Summary of Product Characteristics (SmPC)". (emc). 11 March 2020. Retrieved 30 March 2020.
  3. ^ a b c d e f "Maviret EPAR". European Medicines Agency (EMA). 17 August 2017. Retrieved 30 March 2020.
  4. ^ a b c d e "Mavyret- glecaprevir and pibrentasvir tablet, film coated". DailyMed. 28 January 2020. Retrieved 30 March 2020.
  5. ^ a b "FDA approves Mavyret for Hepatitis C" (Press release). U.S. Food and Drug Administration (FDA). 3 August 2017.
  6. ^ a b c d e "FDA approves treatment for adults and children with all genotypes of hepatitis C and compensated cirrhosis that shortens duration of treatment to eight weeks". U.S. Food and Drug Administration (FDA). 26 September 2019. Retrieved 1 October 2019.
  7. ^ a b British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 620. ISBN 9780857113382.
  8. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  9. ^ a b c d "Drugs@FDA: FDA Approved Drug Products". Food and Drug Administration (FDA). Retrieved 31 October 2017.
  10. ^ Lawitz, Eric J.; O'Riordan, William D.; Asatryan, Armen; Freilich, Bradley L.; Box, Terry D.; Overcash, J. Scott; Lovell, Sandra; Ng, Teresa I.; Liu, Wei (28 December 2015). "Potent Antiviral Activities of the Direct-Acting Antivirals ABT-493 and ABT-530 with Three-Day Monotherapy for Hepatitis C Virus Genotype 1 Infection". Antimicrobial Agents and Chemotherapy. 60 (3): 1546–1555. doi:10.1128/AAC.02264-15. ISSN 1098-6596. PMC 4775945. PMID 26711747.
  11. ^ "enta-10q_20170630.htm". EDGAR. Retrieved 1 November 2017.
  12. ^ Ng, Teresa I.; Krishnan, Preethi; Pilot-Matias, Tami; Kati, Warren; Schnell, Gretja; Beyer, Jill; Reisch, Thomas; Lu, Liangjun; Dekhtyar, Tatyana (May 2017). "In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir". Antimicrobial Agents and Chemotherapy. 61 (5). doi:10.1128/AAC.02558-16. ISSN 1098-6596. PMC 5404558. PMID 28193664.
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