ABT-333

ABT-333 is an inhibitor of non-nucleoside HCV NS5B polymerase.

12 weeks of treatment with ABT-450/r, ABT-333 and ribavirin has been shown the rates of sustained virologic response of 93% to 95% among previously untreated patients and 47% among patients who had not had a response or who had had only a partial response to prior therapy with peginterferon and ribavirin [1]. In addition, in most cases, the studies have been reported that virologic failure was associated with the emergence of variants with substitutions in NS5B, at positions known to confer resistance in vitro to ABT-333 [2].

References:
[1] Kowdley KV1, Lawitz E, Poordad F, Cohen DE, Nelson DR, Zeuzem S, Everson GT, Kwo P, Foster GR, Sulkowski MS, Xie W, Pilot-Matias T, Liossis G, Larsen L, Khatri A, Podsadecki T, Bernstein B.Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med. 2014 Jan 16;370(3):222-32.
[2] Poordad F1, Lawitz E, Kowdley KV, Cohen DE, Podsadecki T, Siggelkow S, Heckaman M, Larsen L, Menon R, Koev G, Tripathi R, Pilot-Matias T, Bernstein B. Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med. 2013 Jan 3;368 (1):45-53.

ABT-450/ ritonavir and ABT-267 in combination with ABT-333 for the treatment of hepatitis C virus.[Pubmed:25800085]

Expert Opin Pharmacother. 2015 Apr;16(6):929-37.

INTRODUCTION: The global prevalence of chronic hepatitis C virus (HCV) is estimated to be 80 - 115 million and currently viremic infections account for 350,000 deaths annually. As the knowledge about HCV evolves, new anti-viral treatments have been developed. The primary goal of antiviral therapies has been to eradicate HCV virus from serum and achieve sustained virologic response (SVR). Historically, interferon has been a staple of nearly all HCV treatment regimens, despite significant toxic effects. AREAS COVERED: In recent years, HCV treatment has changed rapidly and significantly. All-oral treatment regimens show promise for treatment with shorter duration and more manageable side effects. New antivirals aimed at improving SVR may provide a cure to nearly all HCV-infected patients. The unique combination of ABT-450 (paritaprevir) and ABT-267 (ombitasvir) provides highly effective treatment for patients with genotype 1 HCV. This review will examine the antiviral properties, pharmacokinetics, pharmacodynamics, and side effects of these agents. EXPERT OPINION: The combination of ABT-450/r and ABT-267 has improved potency, favorable side effect profile, and low risk of resistance compared to the first-generation protease inhibitors. This combination is likely to be a major part of novel upcoming HCV treatment regimens and is likely to be widely used by clinicians. Additional data is awaited in additional patient populations, and with possible shorter treatment durations.

Dasabuvir (ABT-333) is a nonnucleoside inhibitor of the RNA-dependent RNA polymerase encoded by the HCV NS5B gene, inhibits recombinant NS5B polymerases derived from HCV genotype 1a and 1b clinical isolates, with IC50 between 2.2 and 10.7 nM.

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