Gilead Sciences Inc. announced data from two Phase 2 studies and a compassionate access study in which a regimen containing once-daily Sovaldi (sofosbuvir) 400 mg was administered for the treatment of chronic hepatitis C virus (HCV) infection in patients with advanced liver disease. These data are being presented this week at the 49th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress 2014) in London.
The first study, Study GS-US-334-0125, is an ongoing open-label Phase 2 clinical trial evaluating HCV patients with cirrhosis and portal hypertension, with or without decompensation, who were randomized 1:1 to an immediate treatment arm in which Sovaldi and ribavirin (RBV) was administered for 48 weeks or to a deferred treatment arm in which this regimen was initiated after a 24-week observation period. Eighty percent of participants were treatment-experienced.
Of the 22 patients who completed 24 weeks of therapy, 95% achieved virologic suppression on treatment. Additionally, patients taking Sovaldi-based therapy experienced trends in clinical and laboratory parameter improvements compared to patients in the observation arm. Sovaldi-based therapy was well tolerated in the study, and only one patient discontinued treatment due to an adverse event. The most common adverse events occurring in more than 25% of patients included nausea and pruritis. Patients in both arms of the study will be followed to determine their 12-week sustained virologic response rates (SVR12) after 48 weeks of Sovaldi-based therapy.
Study GS-US-334-0126 was a single-arm open-label Phase 2 trial in which patients with established recurrent HCV infection following liver transplantation received up to 24 weeks of therapy with Sovaldi plus RBV (escalating doses starting at 400 mg/day). The majority of patients had genotype 1-HCV infection and 88% were treatment-experienced.
Seventy percent of patients in this study achieved SVR12. The most common adverse events occurring in more than 20% of patients were fatigue, headache, arthralgia (joint pain) and diarrhea. There were no deaths, graft losses or episodes of organ rejection among post-liver transplantation patients, and no drug-drug interactions were reported between Sovaldi and immunosuppressive agents.
A third, compassionate access study evaluated Sovaldi therapy among 104 post-transplant patients with severe recurrent HCV, including fibrosing cholestatic hepatitis, who had exhausted all other treatment options and received pre-approval access to Sovaldi via Gilead’s compassionate use program. Patients received up to 48 weeks of Sovaldi plus RBV, with some patients also receiving pegylated interferon (peg-IFN) (180 μg/week) at their physician’s discretion. The majority of patients in the study experienced clinical improvements on treatment. Overall, 62% of patients achieved SVR12. Sovaldi-based therapy was well tolerated.
“The patients included in these analyses are historically among the most difficult to cure, and many have had no appropriate treatment options until now,” said Norbert Bischofberger, executive vice president of research and development and chief scientific officer, Gilead Sciences. “These data demonstrate that Sovaldi-based oral therapy can improve outcomes, has a favorable safety profile and is well tolerated among hepatitis C patients with severe liver disease.”
Date: April 11, 2014