1423 Interim Analysis of an Interferon (Ifn)- And Ribavirin (Rbv)-Free Regimen of Daclatasvir (Dcv), Asunaprevir (Asv), and BMS-791325 in Treatment-Naive, Hepatitis C Virus Genotype 1-Infected Patients

Efficacy of an Interferon- and Ribavirin-Free Regimen of Daclatasvir, Asunaprevir, and BMS-791325 in Treatment-Naive Patients With HCV Genotype 1 Infection

“…22,23 An alternative strategy involves combining 2 or more non-nucleotide direct-acting antivirals with or without ribavirin to improve the genetic barrier to resistance. [24][25][26][27] An interferon-free combination of 3 direct-acting antivirals (an NS5B nonnucleoside inhibitor, a ritonavir-boosted protease inhibitor, and an NS5A inhibitor) plus ribavirin showed high SVR rates, but treatment success was reduced when ribavirin or any single direct-acting antiviral was omitted. 27 In this study, combining 3 direct-acting antivirals without interferon or ribavirin showed a high SVR rate after 12 weeks of treatment in HCV GT 1-infected, treatment-naive patients.…”

“…By using the modified intent-totreat analysis (Table 2), 94% (30 of 32) of patients achieved SVR 4 and SVR 12 . Ninety-one percent (29 of 32) of patients achieved SVR 24 and no patient experienced viral breakthrough or post-treatment relapse.…”

“…In this study, daclatasvir, an NS5A replication complex inhibitor, 8 was combined with asunaprevir, an NS3 protease inhibitor, 9 to treat patients with HCV GT 1 who were null responders to prior treatment with peginterferon/ribavirin. 10 This dual combination achieved SVR at 24 weeks after end of treatment (SVR 24 ) in 36% of the patients (2 of 9 patients with GT 1a and 2 of 2 patients with GT 1b). 7 In subsequent studies this dual regimen achieved SVR 24 of 83%-91% in HCV GT 1b null responders, [11][12][13] but a more potent regimen is required for HCV GT 1a.…”

Direct-Acting Antiviral Agents and the Path to Interferon Independence

“…Two additional groups of genotype 1 patients were treated for 24 or 12 weeks with twice the dosage of BMS-791325 and achieved 94% SVR4 and 89% SVR12 respectively. 50 In both three–drug studies, combinations were well-tolerated with only minor constitutional side effects and no serious adverse events. Altogether, the triple DAA combination trials clearly demonstrated that multiple drugs can potentially overcome the necessity for RBV, as well as the adverse impact of unfavorable parameters such as IL28B non-C allele, subtype 1a, and prior NR on the likelihood of SVR.…”

“…50 Asunaprevir, the NNI BMS-791325, and DCV were given to two groups of 16 genotype 1 patients for 24 or 12 weeks. The patient population was well-represented for difficult to treat IL28B non-CC genotypes (72%), AA (25%) and a majority were subtype 1a.…”