Gilead Sciences has announced results from two phase 2 studies evaluating an all-oral treatment regimen of the investigational once-daily nucleotide analogue Sofosbuvir plus Ribavirin ( RBV ) for both the prevention and treatment of recurrent chronic hepatitis C virus ( HCV ) infection among patients who undergo liver transplantation.
HCV infection is the most common cause of liver transplantation in the United States and Europe. Recurrence of HCV infection is universal among patients with active disease at the time of transplantation and up to 50% develop cirrhosis of the liver within five years.
Suppression of HCV RNA prior to liver transplantation should reduce the risk of re-infection and its serious complications, but currently available treatment options are often ineffective and poorly tolerated.
Similarly, in the post-transplant setting, treatment is generally poorly tolerated and complicated by strong drug interactions with immunosuppressive agents used to prevent the body’s rejection of the transplanted liver.
In a study conducted among pre-transplant HCV patients ( Study 2025 ), up to 48 weeks of Sofosbuvir / Ribavirin therapy was administered. Among patients with undetectable HCV ( less than 25 IU/mL ) at the time of transplantation, 64% ( n=25/39 ) achieved undetectable HCV RNA 12 weeks post-transplant ( pTVR12 ).
Patients who achieve pTVR12 are considered cured of HCV infection.
In a second study conducted among post-transplant HCV patients ( Study 0126 ), patients with established recurrent HCV infection following liver transplantation received 24 weeks of Sofosbuvir / Ribavirin therapy. Seventy-seven percent ( n=27/35 ) of patients in this study have achieved a sustained virologic response four weeks post-treatment ( SVR4 ).
Recurrence of HCV following liver transplantation almost always occurs in clinical practice. These patients are at higher risk for disease progression, the development of cirrhosis, liver graft failure, re-transplantation and increased morbidity and mortality.
Three percent and 5% of patients discontinued treatment due to adverse events in the pre- and post-transplant studies, respectively.
No serious adverse events reported were associated with Sofosbuvir.
The most common adverse events observed were consistent with the safety profile of Ribavirin, and included fatigue, anemia, headache and nausea in the pre-transplant study, and fatigue, headache, arthralgia and diarrhea in the post-transplant study.
Study 2025 is an on-going open-label phase 2 study evaluating the efficacy and safety of Sofosbuvir 400 mg once daily plus weight-based Ribavirin for up to 48 weeks or until liver transplantation. Sixty-one patients with HCV infection ( Child-Pugh class A or B cirrhosis ) and liver cancer, who were either treatment-naïve or treatment-experienced were enrolled.
Study 0126 is an ongoing open-label phase 2 study evaluating the efficacy and safety of 24 weeks of treatment with Sofosbuvir 400 mg once-daily plus Ribavirin ( starting at 400 mg/day ) among 40 treatment-naïve and treatment-experienced patients with recurrent HCV infection. Patients in the study had received a transplant a median of four years prior to the study, and 40% were cirrhotic.
There were no deaths, graft losses or episodes of organ rejection among post-liver transplantation patients in the study. ( Xagena )
Source: 64th Annual Meeting of the American Association for the Study of Liver Diseases ( AASLD ), 2013