Glecaprevir/pibrentasvir
 | |
| Combination of | |
|---|---|
| Glecaprevir | NS3/NS4A inhibitor |
| Pibrentasvir | NS5A inhibitor |
| Clinical data | |
| Trade names | Mavyret, Maviret, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a617039 |
| License data | |
| Pregnancy category |
|
| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status | |
| 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.[4][5] It contains glecaprevir and pibrentasvir.[5][6] It works against all six types of hepatitis C.[4] At twelve weeks following treatment between 81% and 100% of people have no evidence of hepatitis C.[7] It is taken once a day by mouth with food.[4][5]
The most common side effects are headache, diarrhea, and tiredness.[7][8] In those with a history of hepatitis B, reactivation may occur.[8] It is not recommended in people with moderate to severe liver disease.[7] Glecaprevir works by blocking the protein NS3/4A protease, while pibrentasvir works by blocking NS5A.[4]
The combination was approved for medical use in the United States and Europe in 2017.[6][4] It is on the World Health Organization's List of Essential Medicines.[9]
Medical uses
[edit]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).[7][5] 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.[5] The duration of treatment was shortened from 12 weeks to eight weeks for many people in 2019.[7]
In the European Union, it is used to treat adults and adolescents aged 12 years and older with chronic (long-term) hepatitis C.[4]
Side effects
[edit]The only known side effects of G/P are hepatitis B reactivation, and more commonly headache, nausea, tiredness, and diarrhea.[10]
Mechanism of action
[edit]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.[10]
History
[edit]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.[10]
Initial identification of glecaprevir was done in a joint effort by AbbVie and Enanta Pharmaceuticals.[11] 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.[12]
The identification and development of pibrentasvir was done by AbbVie.[13]
Research
[edit]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.[10]
References
[edit]- ^ "Glecaprevir / pibrentasvir (Mavyret) Use During Pregnancy". Drugs.com. 10 October 2019. Retrieved 30 March 2020.
- ^ "Liver disease". Health Canada. 9 May 2018. Retrieved 13 April 2024.
- ^ "Maviret 100 mg/40 mg Film-coated Tablets - Summary of Product Characteristics (SmPC)". (emc). 11 March 2020. Retrieved 30 March 2020.
- ^ a b c d e f "Maviret EPAR". European Medicines Agency (EMA). 17 August 2017. Retrieved 30 March 2020.
- ^ a b c d e "Mavyret- glecaprevir and pibrentasvir tablet, film coated". DailyMed. 28 January 2020. Retrieved 30 March 2020.
- ^ a b "FDA approves Mavyret for Hepatitis C" (Press release). U.S. Food and Drug Administration (FDA). 3 August 2017.
- ^ 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.
- ^ a b British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 620. ISBN 9780857113382.
- ^ 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.
- ^ a b c d "Drugs@FDA: FDA Approved Drug Products". Food and Drug Administration (FDA). Retrieved 31 October 2017.
- ^ Lawitz EJ, O'Riordan WD, Asatryan A, Freilich BL, Box TD, Overcash JS, et al. (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. PMC 4775945. PMID 26711747.
- ^ "Enanta Pharmaceuticals Form 10-Q". EDGAR. U.S. Securities and Exchange Commission. Retrieved 1 November 2017.
- ^ Ng TI, Krishnan P, Pilot-Matias T, Kati W, Schnell G, Beyer J, et al. (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. PMC 5404558. PMID 28193664.
