Published in Journal Watch Gastroenterology April 23, 2013
The evidence shows superior efficacy and tolerability of sofosbuvir-based regimens versus those currently available, particularly in patients with HCV genotype 1.
On the heels of the phase II trial results (JW Gastroenterol Apr 12 2013), phase III trial results are now available on sofosbuvir-based regimens for the treatment of chronic hepatitis C virus (HCV) infection in treatment-naive patients. The primary endpoint of the two industry-funded, phase III trials was sustained virologic response at 12 weeks after end of treatment (SVR12).
In the single-group, open-label NEUTRINO trial, 327 patients with HCV genotypes 1 (89%), 4 (9%), 5 (<1%), and 6 (2%) received oral sofosbuvir (400 mg daily), peginterferon (180 µg weekly), and ribavirin (1000–1200 mg daily) for 12 weeks. Among the study group, 17% were black, 71% had IL28B genotype TT or TC, and 17% had cirrhosis. SVR12 was 89% for genotype 1 (92% for genotype 1a and 82% for genotype 1b), 96% for genotype 4, and 100% for genotype 5 or 6. SVR12 was significantly lower for patients with cirrhosis versus without cirrhosis (80% vs. 92%) and for patients with IL28B genotypes TT or TC versus genotype CC (87% vs. 98%). SVR12 did not vary by race or Hispanic ethnicity.
In the open-label FISSION trial, 499 patients with HCV genotypes 2 and 3 were randomized to oral sofosbuvir (400 mg daily) and ribavirin (1000–1200 mg daily) for 12 weeks or peginterferon (180 µg weekly) and ribavirin (800 mg daily) for 24 weeks. Cirrhosis was present in 20% of the sofosbuvir group and in 21% of the control group. In the sofosbuvir group, SVR12 was 97% for genotype 2 and 56% for genotype 3 in the sofosbuvir group compared with 78% for genotype 2 and 63% for genotype 3 in the control group. Noninferiority analysis demonstrated similar efficacy between the two groups. Efficacy among patients with cirrhosis was similar between the sofosbuvir and control groups (47% vs. 38%).
In both studies, resistance did not develop with sofosbuvir treatment. Treatment discontinuation was only 1% to 2% in patients receiving 12-week sofosbuvir regimens with or without interferon compared with 11% in patients receiving the 24-week peginterferon/ribavirin regimen.
Comment: These final results of phase III trials of sofosbuvir in treatment-naive patients with hepatitis C virus genotypes 1 to 6 demonstrate that patients with genotype 1 have excellent treatment response that is superior overall to published response rates for combination therapy and currently available triple therapies. For patients with genotypes 2 and 3, efficacy was similar between an interferon-free sofosbuvir regimen and a standard peginterferon/ribavirin regimen. Furthermore, sofosbuvir is achieving sustained response with a shorter duration of therapy, better tolerability, and no resistance development. The sofosbuvir regimen has recently been submitted to the FDA and, once approved, will usher in the next generation of treatment for HCV infection. A phase III trial of sofosbuvir in patients coinfected with HIV and HCV is ongoing.
Citation(s):
Lawitz E et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013 Apr 23; [e-print ahead of print]. (http://dx.doi.org/10.1056/NEJMoa1214853)
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