Sofosbuvir resulted in a sustained virologic response in 90% of patients infected with hepatitis C virus genotype 1 or 4 at 12 weeks in a phase III trial.
Moreover, in a separate noninferiority analysis, patients with HCV genotypes 2 and 3 taking sofosbuvir had the same rates of sustained virologic response (SVR) as patients taking peginterferon, with fewer side effects, wrote Dr. Eric Lawitz in a report published online April 23 in the New England Journal of Medicine (doi: 10.1056/NEJMoa1214853).
In a report that is also to be presented at the International Liver Congress in Amsterdam, Dr. Lawitz analyzed more than 1,000 previously untreated HCV patients who received treatment with sofosbuvir in two multicenter studies. Sofosbuvir is an investigational nucleotide analogue HCV NS5B polymerase inhibitor.
The first study, the NEUTRINO trial, looked at a single group of 327 patients with genotypes 1, 4, 5, and 6 who received 12 weeks of open-label treatment with sofosbuvir (400 mg/day) plus peginterferon alfa-2a (180 mcg once per week) and ribavirin (given as a divided dose according to body weight, at 1,000 mg/day for patients less than 75 kg and 1,200 mg/day for heavier patients).
Most (89%) of these patients were genotype 1, with 9% having genotype 4, and the remainder having types 5 or 6, according to Dr. Lawitz of the Texas Liver Institute at the University of Texas Health Science Center in San Antonio.
At 12 weeks, SVR, defined by the lower limit of quantification of 25 IU/mL, occurred in 295 of these 327 patients (90%), with little difference in response rate according to genotype.
Having cirrhosis reduced the regimen’s SVR rate to 80%.
The second study assessed by Dr. Lawitz, the FISSION trial, involved 499 patients with HCV genotypes 2 or 3, who were randomized to open-label treatment with either sofosbuvir plus ribavirin for 12 weeks (n = 256) or peginterferon alfa-2a plus ribavirin for 24 weeks (n = 243).
Dosages in the sofosbuvir group were the same as in the NEUTRINO trial; in the peginterferon group, the ribavirin was given as 800 mg/day in two divided doses.
In this analysis, the researchers found that at 12 weeks, both treatment groups had an SVR of 67%.
Once again, the presence of cirrhosis reduced the likelihood of SVR. Genotype 3 also lowered the response, giving SVR rates of 56% in the sofosbuvir group and 63% in the peginterferon group.
In both NEUTRINO and FISSION, deep sequencing analysis of patients taking sofosbuvir who relapsed after having a virologic response showed no evidence of resistance-associated variants.
Discontinuation of sofosbuvir because of adverse events was uncommon in both trials: 2% in the NEUTRINO and 1% in the FISSION.
Indeed, "the influenza-like symptoms and fever that are characteristic of interferon treatment were reported in 16% and 18% of patients receiving peginterferon, respectively, but in only 3% of patients receiving sofosbuvir," Dr. Lawitz and his colleagues wrote.
"Depression, another common side effect of interferon therapy, occurred in 14% of patients receiving peginterferon, as compared with 5% of patients receiving sofosbuvir."
Dr. Lawitz was an investigator in a second, unrelated study to be presented at the International Liver Congress and also reported in the New England Journal of Medicine. In that study, sofosbuvir was again proven to be effective in HCV genotype 2 and 3 patients for whom the traditional peginterferon-ribavirin regimen was not an option. Only the abstract of the study was available at press time (N. Engl. J. Med. 2013 April 23 [doi: 10.1056/NEJMoa1214854]).
The NEUTRINO and FISSION trials were sponsored by Gilead Sciences, maker of sofosbuvir. Dr. Lawitz disclosed financial relationships to Gilead and multiple other pharmaceutical companies. Several authors were employees of Gilead.
