SUMMARY AND COMMENT | GASTROENTEROLOGY
November 15, 2013
Atif Zaman, MD, MPH Reviewing Lawitz E et al., Lancet 2013 Nov 5;
In a phase II trial, a single-tablet, all-oral regimen of sofosbuvir and ledipasvir achieved nearly 100% sustained virologic response in both treatment-naive and treatment-experienced patients.
The FDA should soon approve the interferon-based regimen of sofosbuvir plus peginterferon and ribavirin for the treatment of hepatitis C virus (HCV) genotype 1 infection. Response rates of 90% have been achieved with only 12 weeks of therapy in treatment-naive patients without cirrhosis. The next step in the evolution of therapies for HCV genotype 1 infection is the development of interferon-free regimens.
In this phase II, open-label, randomized trial, investigators evaluated sofosbuvir (a nucleotide polymerase inhibitor; 400 mg) plus ledipasvir (an HCV NS5A inhibitor; 90 mg) in a single combination tablet taken daily with or without ribavirin (1000–1200 mg daily). In one cohort, 60 treatment-naive patients without cirrhosis were randomized to receive sofosbuvir plus ledipasvir alone for 8 weeks or 12 weeks or with ribavirin for 8 weeks. In a second cohort, 40 patients who had previously failed protease inhibitor–based therapy were randomized (stratified by presence or absence of cirrhosis) to receive sofosbuvir and ledipasvir with or without ribavirin for 12 weeks.
In all five treatment groups, rates of sustained virologic response (SVR) were between 95% and 100%. SVR rates were similar with 8 and 12 weeks of therapy. Only two patients (2%; one treatment-naive and one treatment-experienced) had viral relapse after stopping therapy. HCV genotype (1a or 1b), IL28B genotype, black race, and high baseline viral load did not affect SVR. The incidence of adverse events was low; the most common ones were headache, nausea, and anemia.
The results of this small phase II study are impressive. A daily regimen of the single combination tablet of sofosbuvir and ledipasvir with or without ribavirin for 8 to 12 weeks achieved nearly 100% sustained virologic response in both treatment-naive and treatment-experienced patients with genotype 1 hepatitis C virus. This high SVR rate did not seem to be affected by known predictors of negative response. Phase III trial results are eagerly awaited.
EDITOR DISCLOSURES AT TIME OF PUBLICATION
Disclosures for Atif Zaman, MD, MPH at time of publicationSpeaker’s bureauBristol-Myers Squibb; Genentech; Gilead; Kadmon; Merck; Salix; Vertex
Lawitz E et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): An open-label, randomised, phase 2 trial. Lancet 2013 Nov 5; [e-pub ahead of print]. (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962121-2/abstract)
Also See: Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial