Here's the much anticipated BMY abstract on their NS5A/PI combination study. The disparity between the SOC and non-SOC arm will only get worse with time (particularly post-treatment with relapses). At least in nulls with Gen-1 there's a good bet dual therapy with DAAs is not enough. I now agree BMY got ZGEN on the cheap..
Combination therapy with BMS-790052 and BMS-650032 alone or with pegIFN/RBV results in undetectable HCV RNA through 12 weeks of therapy in HCV genotype 1 null responders
BMS-790052 is a potent NS5A inhibitor with broad genotypic coverage while BMS-650032 is a potent HCV NS3 protease inhibitor with coverage of HCV genotypes (GT) 1a and 1b. Clinical studies combining these compounds alone and with pegIFN/RBV are underway in HCV infected null responders to determine their safety and efficacy. Methods: AI447011 is a randomized, open label, Phase 2a study comparing the antiviral activity and safety of BMS-790052 (60 mg QD) and BMS-650032 (600 mg BID) alone (Group A) or with pegIFN/RBV (Group B) for 24 weeks in HCV GT 1 null responders. The primary aim was to determine the proportion of subjects achieving undetectable HCV RNA (<10 IU/mL) at Weeks 2 and 4 of therapy and 24 weeks post-treatment. A Week 12 interim analysis was performed. Results: Twenty-one patients (11 Group A, 10 Group B) were randomized in a sentinel cohort. Median age was 55 years, 13 were male, and 16 were white. Virologic responses are presented in Table 1. 6 (54.5%) Group A subjects experienced viral breakthrough while all subjects in Group B maintained viral suppression. Viral breakthrough occurred exclusively in individuals infected with GT 1a occurring as early as Week 3 and as late as Week 12. The two GT 1b subjects in Group A remained HCV RNA undetectable. The 6 subjects with breakthrough had pegIFN/RBV added to their regimen. HCV RNA fell to UD in 2 subjects and to < 25 IU/mL in another 2 subjects while the other 2 had = 1.5 log decreases in HCV RNA. No deaths, SAEs, or discontinuations due to AEs were recorded during the analysis period. Diarrhea was the most common AE and was mainly mild to moderate in severity. Conclusions: Treatment with BMS-790052 and BMS-650032 with or without PegIFN/RBV demonstrated similar RVR rates in HCV infected GT 1 null responders. 6/11 subjects receiving 2 direct antiviral agents alone experienced viral breakthrough by Week 12 while a four-drug combination maintained viral suppression in all subjects. Should this activity predict SVR, these results will have significant implications for future combination HCV antiviral therapy.
Table 1: Virologic responses by treatment Group A
BMS-650032 and BMS-790052
n=11 Group B
BMS-650032, BMS-790052, pegIFN/RBV
n=10
Genotype 1a
n 9 9
Median baseline HCV RNA IU/mL 6.9 log10 6.7 log10
Median HCV RNA decline Week 2 IU/mL -5.1 log10 -5.3 log10
RVR*
n (%) 7 (63.6%) 6 (60%)
eRVR*
n (%) 4 (36.4%) 6 (60%)
cEVR*
n (%) 5 (45.5%) 9 (90%)**
*Intent-to-treat analysis, breakthrough = failure ** One subject with HCV RNA < 25 IU/mL at Week 12, undetectable (UD, <10 IU/mL) on retesting RVR=UD by Week 4 eRVR=UD at Weeks 4 and 12 cEVR=UD by Week 12
AI
