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Investigational Antiviral Drugs
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
John Mills, Suzanne M. Crowe, Marianne Martinello
Beclabuvir (BMS-791325), a NS5B nonnucleoside polymerase inhibitor, completed phase IIb clinical trials in combination with daclatasvir and asunaprevir, with SVR12 values of 91% in treatment-naive and -experienced participants with HCV GT-1 (Poordad et al., 2015). It appeared to have good activity toward HCV GT-1, GT-3, GT-4, and GT-5 but weaker to GT-2 and GT-6. Monotherapy at 600 to 900 mg/day reduced HCV RNA levels by ≥ 6 log10. However, given the competitive rapidly evolving field of HCV therapeutics, Bristol Myers Squibb has suspended drug development, given limited clinical utility and suboptimal efficacy (Everson et al., 2016; Gentile et al., 2015; Poordad et al., 2015).
NS5B polymerase inhibitors in phase II clinical trials for HCV infection
Published in Expert Opinion on Investigational Drugs, 2018
Guglielmo Borgia, Alberto Enrico Maraolo, Salvatore Nappa, Ivan Gentile, Antonio Riccardo Buonomo
Inhibition of NS5B polymerase is a key antiviral mechanism. Both nucleoside and non-nucleoside NS5B inhibitors co-exist in the anti-HCV armamentarium: the first have, when compared with the latter, higher genetic barrier resistance more antiviral potency. Apart from the combination Grazoprevir/Elbasvir, all the regimens recommended by the most recent European and American guidelines include a NS5B polymerase inhibitor, namely Sofosbuvir or Dasabuvir [4,5]. Another drug belonging to this class and having completed a phase 3 trial is Beclabuvir [51], which, combined with other DAAs, turned out to be effective in GT1-infected Japanese patients [52], and it is also under investigation as part of complex regimens to shorten anti-HCV treatment duration until to just 4 weeks [53]. So, is there still room for other members of this class? This is neither a mere moot point nor a quixotic attempt to pursue the development of a ‘perfectovir’ [54]. At the threshold of the ‘precision medicine’ [55], it is mandatory to guarantee a tailored treatment to HCV patients, possibly RBV-free, as some of the new regimens promise [56], and especially when first-line regimens fail [57]. Novel NS5B polymerase inhibitors may serve as backbone of future ‘salvage’ therapies, particularly in patients that exerted the rare S282 mutation conferring resistance to Sofosbuvir or Y93 NS5A mutations the ones that confer resistance to the majority of now available NS5A inhibitors [58].
Efficacy and safety of a fixed dose combination tablet of asunaprevir + beclabuvir + daclatasvir for the treatment of Hepatitis C
Published in Expert Opinion on Pharmacotherapy, 2020
Emanuela Zappulo, Riccardo Scotto, Antonio Riccardo Buonomo, Alberto Enrico Maraolo, Biagio Pinchera, Ivan Gentile
This review focuses on an all-oral fixed-dose combination of daclatasvir (DCV, 30 mg), a NS5A inhibitor; asunaprevir (ASV, 200 mg), an NS3 protease inhibitor; and beclabuvir (BCV, 75 mg), a non-nucleoside NS5B inhibitor, formulated as a single film-coated twice-daily tablet (Ximency®, Bristol-Myers Squibb) (see Drug summary Box 1) .