Second Study Confirms Safety and Efficacy of Interferon-free HCV Combination

Study results show that the interferon-free regimen of simeprevir plus sofosbuvir achieves high rates of sustained virologic response and has a strong safety profile for patients with hepatitis C.

A study in Gastroenterology suggests that the interferon-free regimen of simeprevir plus sofosbuvir achieves high rates of sustained virologic response (SVR) and has a strong safety profile for patients with hepatitis C virus (HCV). The findings mirror an earlier Phase II study and add another layer of evidence that HCV treatment without interferon can be safe and effective.

In late 2014, the Food & Drug Administration approved the combination of simeprevir (Janssen’s Olysio) and sofosbuvir (Gilead’s Sovaldi) for the treatment of hepatitis C. The combination is potentially advantageous, because it can be be used without ribavirin or pegylated interferon-alfa, which have been the mainstays of HCV therapy, but that can be difficult for patients to tolerate and potentially dangerous in some cases. Simeprevir plus sofosbuvir had been used off-label together prior to the FDA decision last October.

The current study was a large, prospective observational cohort study in which 836 patients with HCV genotype 1 infection were given, a 12 week regimen of simeprevir plus sofosbuvir. Most of the patients in the trial had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%).

The primary outcome was SVR, defined as level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment-a 2 week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias.

The overall rate of SVR rate was 84% (675/802 patients, 95% CI: 81-87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively.

The findings mirror those of the COSMOS trial, a phase II study published in The Lancet in 2014, in which patients took the combination with or without ribavirin for 12 or 24 weeks. That study found that 91% of patients who received the combination with ribavirin reached treatment success (defined as no detectable HCV RNA 12 weeks after treatment) compared with 95% of those who did not take ribavirin.

Among those who got 12 weeks of treatment, 94% reached treatment success compared with those who received 24 weeks. Common side effects included fatigue, headache, nausea, insomnia, pruritus, rash, and photosensitivity. Patients treated for 24 weeks also reported dizziness and diarrhea.