Bristol-Myers Squibb has reported the Phase II clinical trial results of direct-acting antiviral (DAA) therapy in patients with hepatitis C virus (HCV) genotype 1 who had not responded to prior therapy with PEG-interferon alfa and ribavirin.
The open-label Phase IIa study evaluated the antiviral activity and safety of the combination of Daclatasvir and Asunaprevir with and without PEG-Interferon alfa and ribavirin in 21 HCV genotype 1 null responders. Daclatasvir is an inhibitor of NS5A replication complex, while Asunaprevir is an investigational, oral, selective NS3 protease inhibitor.
In the Phase II study of dual DAA Therapy with Daclatasvir and Asunaprevir (Group-A) 11 patients were randomised to receive dual DAA therapy for 24 weeks. Seven of the 11 patients achieved undetectable viral load by week four and five patients remained undetectable at the end of treatment.
The study demonstrated that DAA therapy containing Daclatasvir and Asunaprevir achieved primary endpoint of sustained virologic response 12-weeks post-treatment (SVR12). This was the first study to demonstrate the possibility that hepatitis C can be cured without the use of interferon. It showed that 100% of the difficult-to-treat patients dosed with quadruple therapy containing Daclatasvir and Asunaprevir in combination with PEG-Interferon alfa and ribavirin achieved SVR12.
In the trial, 36% of the patients showed sustained virological response at 12 weeks post-treatment, and in follow-up 48 weeks post treatment, no additional cases of viral relapses were observed.
In the quadruple therapy with Daclatasvir, Asunaprevir and PEG-Interferon alfa and ribavirin (Group-B), ten patients were randomised to receive quadruple therapy for 24-weeks and found that six patients achieved undetectable HCV RNA by week four, and all the ten were undetectable by the end of treatment, and achieved SVR12.
Lead investigator of the study Anna Lok said the data seen in the study with Bristol-Myers Squibb's investigational DAAs Daclatasvir and Asunaprevir, either as DAA-only therapy or as part of quadruple therapy, are encouraging to advance hepatitis C therapy for the difficult-to-treat patient population.