15 The SPRINT-2 trial evaluated BOC in two cohorts of treatment-naïve patients:

Caucasian and black patients.12 The number of patients in the black cohort was small in comparison to that of the Caucasian cohort and may have been insufficient to provide an adequate assessment of true response in this population. All patients were first treated with PegIFN alfa-2b and weight-based RBV as lead-in therapy for a period of 4 weeks, followed by one of three regimens: Dabrafenib concentration (1) BOC, PegIFN, and RBV that was administered for 24 weeks if, at study week 8 (week 4 of triple therapy), the HCV RNA level became undetectable (as defined in the package insert as <10-15 IU/mL), referred to as response-guided therapy (RGT); if, however, HCV RNA remained detectable at any visit from week 8 up to but not

including week 24 (i.e., a slow virological response), BOC was discontinued and the patient received SOC treatment for an additional 20 weeks (2) BOC, PegIFN, and RBV administered for a fixed duration of 44 weeks; and (3) PegIFN alfa-2b and weight-based RBV alone continued for an additional 44 weeks, representing SOC therapy.12 The BOC dose was 800 mg, given by mouth three times per day with food. The overall SVR rates were higher in the BOC arms, (63% and 66% respectively) than in the SOC arm (38%), but differed according to race (Fig. 1). The SVR rates among Caucasian patients were 67% in the RGT, 69% in the fixed duration, ITF2357 clinical trial and 41% in the SOC arms, respectively.12 In black patients, the SVR rates were 42% in the RGT, 53% in the fixed duration, and 23% in the SOC arms, respectively (Fig. 1).12 A total of 54% of Caucasian recipients of BOC experienced a rapid

virological response (RVR; HCV RNA undetectable, <10-15 IU/mL at week 8, this interval selected because medchemexpress of the 4 week lead-in). By contrast, only 20% of black recipients of BOC experienced an RVR. Regardless of race, among those patients who became HCV RNA negative at week 8 (∼57% in both BOC arms and 17% in SOC arm), the SVR rates were 88% in the RGT arm, 90% in the fixed duration arm and 85% in the arm treated by SOC, compared to SVR rates of 36%, 40%, and 30%, respectively, if HCV RNA remained detectable at week 8 (Fig. 2).12 In subgroup analysis, SVR rates were higher in BOC-containing regimens across all the pretreatment variables that had been identified in previous studies to influence response to SOC therapy, including advanced fibrosis, race, and high pretreatment HCV viral load. Moreover, the SVR rate in subgroups was similar in both the RGT and fixed duration arms and therefore, the AASLD and the FDA support the use of RGT for treatment-naïve patients without cirrhosis. The FDA recommends that patients with compensated cirrhosis should not receive RGT, however, this is based on limited data and requires further study. Of note, if the virological response did not meet criteria for RGT, i.e.