Gilead Sciences, 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 (Oral #068), is an ongoing open-label Phase 2 clinical trial evaluating HCV patients with cirrhosis and portal hypertension, with or without decompensation, who were randomised 1:1 to an immediate treatment arm in which Sovaldi and ribavirin (RBV) was administered for 48 weeks (n=25) or to a deferred treatment arm in which this regimen was initiated after a 24-week observation period (n=25). 80 per cent of participants were treatment-experienced.
Of the 22 patients who completed 24 weeks of therapy, 95 per cent (n=21/22) 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 per cent 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 (n=33/40) and 88 per cent (n=35/40) were treatment-experienced.
70 per cent (n=28/40) of patients in this study achieved SVR12. The most common adverse events occurring in more than 20 per cent of patients were fatigue, headache, arthralgia (joint pain) and diarrhoea. 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 per cent 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, PhD, executive vice president of research and development(R&D) and chief scientific officer, Gilead Sciences. “These data demonstrate that Sovaldi-based oral therapy can improve outcomes, has a favourable safety profile and it is well tolerated among hepatitis C patients with severe liver disease.”
Sovaldi is an oral nucleotide analog inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. Sovaldi is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication.
Sovaldi was approved in the United States on December 8, 2013 and in the European Union on January 17. In the United States, Sovaldi is approved for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen.
Efficacy has been established in subjects with HCV genotype 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection.
Treatment response varies based on baseline host and viral factors. Monotherapy is not recommended for treatment of chronic hepatitis C. Studies GS-US-334-0125 and GS-US-334-0126 evaluated investigational uses of Sovaldi, for which safety and efficacy have not yet been established.