Major Breakthrough in Hepatitis C Therapy: Daclatasvir and Sofosbuvir Combination Attains Functional Cure in More Than 90% of Patients with Hepatitis C
Michael R. Page, PharmD, RPh
Combination therapy using Bristol-Myers Squibb’s daclatasvir and Gilead Sciences Inc’s sofosbuvir has attained a sustained viral response 12 weeks after the end of treatment (SVR12) in more than 90% of patients with hepatitis C, regardless of prior treatment.
A major breakthrough in hepatitis C virus (HCV) treatment was announced in an article released on January 16 by the New England Journal of Medicine. The combination of the NS5A replication complex inhibitor daclatasvir (Bristol-Myers Squibb) and the nucleotide analogue HCV NS5B polymerase inhibitor sofosbuvir (Gilead Sciences Inc) in patients with genotype-1, -2, or -3 hepatitis C virus resulted in a sustained viral response 12 weeks after the end of treatment (SVR12) greater than 90% in several different populations.
Investigators found robust efficacy in both treatment-naive patients and patients who had experienced virologic failure with either telaprevir or boceprevir in combination with peginterferon alfa and ribavirin. Dr. Sulkowski and colleagues tested the combination, with and without ribavirin, in 211 patients. Of treatment-naive patients with genotype-1 HCV infection, 98.4% of 126 patients experienced SVR12 and 95.2% experienced SVR24. Results in genotype-2 and -3 infection were also strong. Ninety-three percent of treatment-naive patients with genotype-2 or -3 HCV infection experienced SVR12, which was maintained with a 93.3% SVR24 rate. Among treatment-experienced patients, SVR12 occurred in 98% of patients with genotype-1 HCV and 91% of patients with genotype-2 and -3 HCV.
Patients receiving ribavirin did not attain higher response rates than patients receiving daclatasvir and sofosbuvir therapy alone. Ribavirin-free patients attained a 98% rate of SVR12, while patients receiving ribavirin, daclatasvir, and sofosbuvir attained a 94% SVR12 rate. Ribavirin is a pregnancy category X medication that may cause blood dyscrasias.
This all-oral, ribavirin-free, interferon-free regimen shows functional cure rates in excess of 90%, even among treatment-experienced patients. In the trial, most adverse events were mild to moderate, with fatigue, headache, and nausea among the most common adverse events. The high-powered combination of these 2 medications from Bristol-Myers Squibb and Gilead Sciences Inc may mean rapid change in the way hepatitis C is treated.