An dual oral therapy regimen consisting of daclatasvir and simeprevir, without interferon or ribavirin, produced sustained virologic response in 85% to 95% of patients with hepatitis C virus genotype 1b disease, but not genotype 1a, LEAGUE-1 study findings indicate.

Christophe Hézode from Hôpital Henri Mondor in Paris and colleagues assessed the safety and efficacy of 30 mg daclatasvir (Bristol-Myers Squibb) plus 150 mg simeprevir (Olysio, Janssen) once-daily with or without ribavirin for treatment-naive patients (n=104) or prior null responders (n=43) with genotype 1b chronic HCV.

The researchers conducted additional analyses in a subset of 21 patients with harder-to-treat HCV genotype 1a. Hézode presented the data from the open-label, multicenter European study at the 2014 Conference on Retroviruses and Opportunistic Infections.

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 After 12 weeks of treatment patients were re-randomised to either stop all treatment or continue their assigned regimen for an additional 12 weeks. In the smaller exploratory analysis, all participants with genotype 1a received daclatasvir, simeprevir and ribavirin for 24 weeks.


Among the 53 genotype 1b treatment-naive participants, sustained virological response rates at 12 weeks after completing treatment (SVR12) were 85% with the dual daclatasvir and simeprevir regimen, and 75% with the triple daclatasvir, simeprevir and ribavirin regimen in an intent-to-treat analysis. In an observed analysis excluding people with missing data at week 12, the SVR12 rates were 90% and 83%, respectively.



Among genotype 1b null responders in the non-ribavirin group, SVR12 was 65% and 95% among patients assigned to the ribavirin-containing regimen.


Among those with genotype 1a, 66.7% achieved SVR12. Null responders were assigned to pegylated interferon/ribavirin plus daclatasvir and simeprevir as rescue therapy.


When analyzing outcomes by treatment duration, 83% of null responders who took the dual regimen for 12 weeks and 50% treated for 24 weeks achieved SVR12. Among those who took the triple regimen, SVR12 rates were 100% for 12 weeks and 89% for 24 weeks.


The most commonly reported serious adverse events were neurotoxicity and liver disorder. However, mortality from unrelated intracranial hematoma was reported in one patient.


“Further direct-acting antiviral agents combination studies, including those with simeprevir, are using the recommended daclatasvir 60 mg dose,” Hézode said during a presentation.


Daclatasvir is a NS5A inhibitor that has shown promise in other combination treatment regimens used to treat HCV, one such of which is with the recently approved protease inhibitor sofosbuvir. The drug is currently classified as a breakthrough therapy in combination with asunaprevir and is undergoing FDA expedited review.



Zeuzem S. Abstract #28LB. Presented at: CROI 2014; March 3-6, 2014; Boston.

 Disclosure: Hezode reports no disclosures.