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ION 2: Longer sofosbuvir/ledipasvir treatment may be unnecessary in previous failures
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LONDON — Twelve weeks of treatment with the fixed-dose combination of Gilead’s sofosbuvir and ledipasvir — without ribavirin — may be sufficient to treat patients with hepatitis C virus who had failed previous therapies, according to findings presented here.
Nezam Afdhal, MD, of the Beth Israel Deaconess Medical Center in Boston, presented findings for 440 patients from the phase 3 ION-2 study, which investigated the fixed-dose formulation of sofosbuvir (Sovaldi) 400 mg/ledipasvir 90 mg in treatment-experienced patients with genotype 1 disease. The study included four patient cohorts: those treated for 12 weeks with or without ribavirin and those treated for 24 weeks with or without ribavirin.
“We wanted to answer the question of whether a longer duration of therapy is necessary to achieve high [sustained virologic response] rates,” said Afdhal, a member of the HCV Next Editorial Board.
Eligible participants had failed therapy with pegylated interferon and ribavirin or a protease inhibitor with that regimen.
Sustained virologic response at 12 weeks (SVR12) served as the primary outcome measure. The secondary endpoint was safety.
There were 109 patients in the group that was treated for 12 weeks without ribavirin and 111 treated for 12 weeks with ribavirin. For the 24-week group, 109 were treated without ribavirin and 111 were treated with ribavirin.
The SVR12 rate for the 12-week, non-ribavirin group was 94%. For 12 weeks of the combination with ribavirin, SVR12 was 96%. For 24 weeks of treatment, SVR12 rates were 99% in the non-ribavirin group and 99% in the ribavirin group.
Breaking down the results further, among patients who failed previous therapy on pegylated interferon and ribavirin, 12 weeks of therapy yielded a 96% SVR12 rate, and 24 weeks of therapy yielded a 98% SVR12 rate.
One patient experienced virologic failure. Fourteen percent of previous failures had NS5A variants, according to Afdhal. There was an 89% SVR12 rate in this group.
Grade 3 or 4 adverse events were similar across the groups.
“Numerically, there were more grade 3 to 4 adverse events in the longer duration of therapy,” Afdhal said, adding that there were no deaths. Laboratory abnormalities occurred more frequently in patients treated with ribavirin. Those events included fatigue, rash and irritability.
“We conclude that adding ribavirin or extending treatment to 24 weeks did not significantly improve SVR rates,” Afdhal said. “The presence of NS5A mutation had minimal clinical effect on SVR.”
Afdhal added that ribavirin did not alter viral kinetics or prevent relapse.
“Extending treatment doesn’t make clinical or fiscal sense,” Afdhal said. “We should not over-treat these patients. Twelve weeks in cirrhotics and treatment failures or treatment-naive patients makes the most sense.”
For more information:
Afdhal N. N Engl J Med. 2014;doi:10.1056/NEJMoa1402454.
Disclosure: Afdhal reports no relevant financial disclosures.