FUSION Trial: SOF Plus RBV Shows Superior SVR rates in HCV Treatment-experienced Patients Compared to the Historical Control Rate

12 Aug, 16

Introduction

Currently there are no treatment alternatives for chronically HCV-infected patients who are intolerant, ineligible or unwilling to receive interferon therapy. Sofosbuvir is a potent uridine nucleotide analogue that inhibits HCV polymerase. It has demonstrated high sustained virological response rates in treatment-naive patients with genotype 2/3 HCV.

Aim

To assess the efficacy and safety of sofosbuvir administered with ribavirin in HCV patients with genotype 2 or 3 and for whom treatment with peginterferon was not an option.

Patient Profile

N = 201 HCV-monoinfected patients
HCV genotype: 2 (34%); 3 (63%)
IL28B genotype: 70% non-CC
Prior treatment failure: 75% relapse; 25% nonresponse
Age and sex: mean age 54 (range 24-70); 70% male
Race: 87% white; 3% black
Liver disease: 34% had cirrhosis
Treatment-experienced (failed prior interferon-based therapy)
HCV RNA ≥ 10,000 IU/ml

Method

Randomized, controlled, blinded phase 3 trial comparing 12 and 16 weeks of sofosbuvir + ribavirin in treatment-experienced HCV GT 2 or 3

Drug Dosing
Sofosbuvir: 400 mg once daily
Weight-Based Ribavirin (in 2 divided doses): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg

Primary End-Point

SVR12 (Sustained Virologic response at 12 weeks)

Results

The rates of sustained virologic response achieved with sofosbuvir and ribavirin were superior to the historical control rate of 25%, 50% in the 12-week group and 73% in the 16-week group (P<0.001 for each comparison).
16 weeks of treatment showed significantly higher rate of SVR than patients receiving 12 weeks of treatment (P<0.001)
No patient receiving sofosbuvir in study had virologic breakthrough during treatment or failed to have a response to treatment

HCV genotype 3 showed significantly lower response rates in both the groups compared to HCV genotype 2

Cirrhosis was associated with a decreased rate of sustained virologic response in both the treatment groups

The overall safety profile in patients receiving 16 weeks of therapy was similar to 12 weeks of therapy

Conclusion

Twelve weeks of treatment with sofosbuvir and ribavirin can be an effective option for patients with HCV genotype 2 infection. However, for patients with genotype 3 infection, particularly cirrhotics or who have not had a response to prior treatment with interferon, extending the duration of treatment to 16 weeks may provide an additional benefit.

N Engl J Med 2013; 368:1867-77