SummaryName:ParitaprevirSynonyms:Veruprevir; ABT-450; ABT450; ABT 450Sponsor:Abbott / AbbVie (global presence)Co-Sponsor:Enanta Pharmaceuticals (USA)Type of product:InhibitorViral family:FlaviviridaeStatus:
Market / Licensed for use
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Paritaprevir
Synonyms:Veruprevir; ABT-450; ABT450; ABT 450
Sponsor:Abbott / AbbVie (global presence)
Co-Sponsor:Enanta Pharmaceuticals (USA)
Type of product:Inhibitor
Mode of action:Protease Inhibitor (PI)
Viral family:Flaviviridae
Virus:HCV (Hepatitis C virus)
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DetailsCharacteristics:Small, orally bioavailable molecule, acylsulfonamide derivative acting as inhibitor of HCV protease;
Subnanomolar potency in enzyme inhibition assays and antiviral activity in replicon system;
Developed for use in combination therapy for treatment of chronic HCV infection
Ref.: Carrion AF et al., Expert Opin Pharmacother. 2014 Apr;15(5):711-6 (www.ncbi.nlm.nih.gov/pubmed/24517400); Gentile I et al., Curr Med Chem. 2014;21(28):3261-70. Review. (www.ncbi.nlm.nih.gov/pubmed/25005190); Asselah T. J Hepatol. 2013 Oct;59(4):885-8 (www.ncbi.nlm.nih.gov/pubmed/23707374); Zeng QL et al., World J Gastroenterol. 2013 Jun 7;19(21):3199-206. Review. (www.ncbi.nlm.nih.gov/pubmed/23745021) PK Data, Dosage or Route of Administration:Cpnds of this family have reportedly a good bioavailability supporting potential once-daily dosage; Co-administration of ABT-450 with Ritonavir increases Cmax and AUC of ABT-450 by factor of 28- to 48-fold
Ref.: Gentile I et al., Curr Med Chem. 2014;21(28):3261-70. Review. (www.ncbi.nlm.nih.gov/pubmed/25005190) In vivo and clinical data:Phase IIa (M11-602) study was a randomized, placebo-controlled, blinded, dose-ranging trial evaluating safety and antiviral activity of ABT-450 boosted with Ritonavir in HCV-infected (80% with viral genotype 1a), treatment-naive pts:
Results of the monotherapy phase (3 day-treatment with ABT-450/Ritonavir) were presented at 61st Annual Meeting of AASLD, Oct. 29-Nov. 2, 2010 by Lawitz et al., Poster 1855:
Results of the first 4 weeks of combined therapy with ABT-450/Ritonavir and PEG-IFN/Ribavirin were presented at 61st Annual Meeting of AASLD, Oct. 29-Nov. 2, 2010 by Lawitz et al., Poster LB10:
Results of an open-label Phase II pilot study ("Pilot" study NCT01221298, M12-267) evaluating a combination of ABT-450 (boosted with Ritonavir, ABT-450/r) with ABT-072 and Ribavirin were announced by Abbott on Apr. 19, 2012, and presented by Lawitz et al. at the 47th Annual Meeting of the EASL, Apr. 18–22, 2012, Barcelona, Spain (Abstract 13):
Results of an open-label Phase II pilot study (NCT01306617) evaluating a combination of ABT-450 (boosted with Ritonavir, ABT-450/r) with ABT-333 and Ribavirin were presented by Poordad et al. at the 47th Annual Meeting of the EASL, Apr. 18–22, 2012, Barcelona, Spain (Abstract 1399):
On Apr. 23, 2013, AbbVie announced additional results from Aviator Phase IIb study (M11-652, NCT01464827) evaluating safety and efficacy of combination of ABT-450 boosted with Ritonavir (dosed 100/100 to 200/100 mg QD), ABT-267 (25 mg QD), ABT-333 (400 mg BID) and Ribavirin (weight-based dosing) administered for 8, 12 or 24 weeks to chronic HCV genotype 1-infected, non-cirrhotic treatment-naive pts and prior PEG-IFN/Ribavirin null responders;
Interim 12-week results of ongoing Phase III study for the same drug combination (ABT-450/Ritonavir, ABT-267, ABT-333 and Ribavirin) were also announced by sponsor on Apr. 23, 2013:
Data from ongoing Phase III Sapphire-1 (NCT01716585) were published by Feld JJ et al., N Engl J Med. 2014 Apr 24;370(17):1594-603 (www.ncbi.nlm.nih.gov/pubmed/24720703):
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Development status
Market / Licensed for use
Approved for market in US (Dec. 2014)and other markets as part of combination therapy called Viekira Pak; See Remarks RemarksNS3/4A HCV serine protease inhibitors;
Abbott's antiviral program is focused on HCV;
Phase II studies consisted in evaluation of ABT-450 combined with other cpnds from sponsor, together with/without PEG-IFN/Ribavirin in HCV-infected treatment-naive or experienced pts;
A Phase III study with drug combination ABT-450/Ritonavir, ABT-267, ABT-333 and Ribavirin is ongoing;
On May 6, 2013, AbbVie announced that its investigational direct-acting antiviral (DAA) combination ABT-450/Ritonavir + ABT-267 + ABT-333 with and without Ribavirin, has been designated as Breakthrough Therapy by FDA for treatment of genotype 1 (GT1) HCV infection;
NDA was filed by AbbVie to FDA in Apr. 2014 for US market, for combination therapy consisting of ABT-267 (Ombitasvir), ABT-333 (Dasabuvir) and ABT-450/Ritonavir (combination was called Viekira Pak);
FDA approval for US market of Viekira Pak was announced in Dec. 2014 |