The Real-World Experience With Simeprevir- and Sofosbuvir-Based Regimens in Hep C Treatment

On the third day at The Liver Meeting 2014, an annual event by the American Association for the Study of Liver Disease, held in Boston, Massachusetts, from November 7 to 11, 2014, Bashar A. Aqel, MD, Mayo Clinic in Phoenix, Arizona, presented results from phase 2 of the COSMOS (Combination of SiMeprevir and sOfosbuvir in hepatitis C (HCV) genotype 1 [GT1] infected patientS) trial. The talk, entitled “The use of simeprevir and sofosbuvir to treat HCV GT1 in the liver transplant setting: the experience in 3 US centers” presented results from “real world” patients, and suggested that hepatitis C virus GT1 infection can be treated effectively with a combination of sofosbuvir (SOF) and simeprevir (SMV), with or without ribavirin (RBV), to achieve SVR4 as well as SVR12. The regimen is suitable for interferon (IFN) ineligible patients and those who have failed prior treatment with advanced fibrosis.

The objective of the study was to report the experience of treating IFN ineligible/prior treatment failure patients with SOF/SMV combination in 3 US liver transplant (LT) centers, using sustained virological response (SVR) as a readout for treatment efficacy.

Dr Aqel explained that across the 3 centers, 147 patients with GT1 disease who required this IFN-free treatment were identified. To date, of the 147 patients, 141 (96%) have completed treatment; 105 patients achieved SVR4 and 87 achieved SVR12. The trial to date has 16 treatment failures (11%), 14 had virologic failure. Of the 14 who failed treatment, 12 relapsed within 4 weeks (~86%). One patient died at 6 weeks after completing treatment due to progressive liver disease.

Overall, SVR4 was achieved in 87% of patients and SVR12 in 84% of patients.

According to Dr Aqel, cirrhosis was responsible for lack of response for both SVR4 and SVR12. As was observed with some of the other SOF/SMV studies, RBV did not influence response rate—a similar response rate was observed with and without RBV. Further, viral load did not influence the patient response rate, SVR4 or SVR12. SVR was also independent of treatment status; both treatment-naïve and experienced patients had similar SVR. However, Dr Aqel noted that patients infected with genotype 1b hepatitis C had a tendency to respond better to treatment, although the results were not statistically significant.

Of the current cohort that were treated, 4 patients received LT—all after SVR4. Of the 4, 3 continued to be SVR post-LT, while 1 relapsed and continues to be viremic.

Again, similar to results from other studies being presented with this drug combination, total adverse events—observed in 10% of patients—were mild and did not necessitate treatment discontinuation. Four patients had hyperbilirubinemia and 2 had low-grade anemia.

According to Dr Aqel, based on the study results so far, SMV/SOF combination has been well tolerated in their difficult-to-treat population of patients, a majority of whom are cirrhotic, and who are ineligible, previously intolerant, or non-responsive to IFN-based therapy. No episodes of hepatic decompensation were documented with this regimen to date. Overall SVR12 is 84% and is highest in non-cirrhotic patients and RBV did not impact SVR rate. Dr Aqel concluded that SVR4 can be a strong predictor of long-term virologic response in HCV-infected patients.