Bristol-Myers Squibb ( BMS ) has announced interim results from a phase II open-label study of Daclatasvir, NS5A replication complex inhibitor, and GS-7977, a nucleotide NS5B polymerase inhibitor, in treatment-naïve patients with hepatitis C genotypes 1, 2 and 3. In this interim analysis, a combination of the two oral, once-daily investigational compounds taken for 24 weeks, with or without Ribavirin, achieved a rapid and sustained viral response. Overall, 100% of patients with genotype 1, 2, or 3 HCV achieved viral load below the lower limit of quantification at week 4 on treatment. In the genotype 1 HCV treatment groups, 100% of patients achieved sustained virologic response through four weeks off-treatment ( SVR4 ). In the genotypes 2 and 3 treatment groups, 91% ( 40/44 ) of patients achieved SVR4.

The most frequent ( greater than or equal to 25% overall ) adverse events on treatment, based upon the most recent 12-week interim safety analysis, were fatigue, headache and nausea.
Drug-related adverse events were generally mild and did not lead to treatment discontinuation.
Grade 3-4 laboratory abnormalities occurring in patients in the Ribavirin treatment groups included anemia, elevated glucose, elevated fasting glucose, lymphopenia and low serum phosphorus, and the grade 3-4 laboratory abnormalities reported in the Ribavirin-sparing treatment groups were low phosphorus and elevated cholesterol.

This phase II study ( AI444-040 ) was designed to evaluate the potential to achieve sustained virologic response with an oral, pan-genotypic, once-daily treatment regimen combining Daclatasvir ( DCV ) and Gilead Sciences’s GS-7977, with or without Ribavirin, in patients chronically infected with HCV genotypes 1, 2 and 3.
In the initial phase of this study, patients were randomized into six groups, evaluating three different dosing schedules in patients with HCV genotype 1 ( n=44 ) and in patients with HCV genotype 2 or 3 ( n=44 ).

Dosage and administration: GS-7977 400 mg QD for 7 days then DCV 60 mg QD + GS-7977 400 mg QD for 23 weeks; DCV 60 mg QD + GS-7977 400 mg QD for 24 weeks; DCV 60 mg QD + GS-7977 400 mg QD + Ribavirin for 24 weeks .

The study was subsequently expanded to include four new treatment arms that evaluate HCV genotype 1 patients who have previously failed Telaprevir or Boceprevir treatment, and shorter duration of therapy in treatment-naïve HCV genotype 1 patients.

The primary endpoint of the study is sustained virologic response 12 weeks post-treatment ( SVR12 ). An interim analysis for safety and antiviral activity was conducted at 12 weeks on-treatment. An additional interim analysis for antiviral efficacy was conducted four weeks post-treatment.

Source: Bristol-Myers Squibb, 2012

XagenaMedicine2012