A combined regimen of daclatasvir and sofosbuvir achieved sustained virologic response rates greater than 90% in an industry-sponsored trial involving patients with chronic HCV, according to study published online Jan. 16 in the New England Journal of Medicine.
The once-daily oral treatment was effective against HCV type 1 among patients with any viral subtype, as well as among patients who had failed to respond to or had developed resistance to protease inhibitors. The latter group currently has no other treatment options. It also was effective against HCV types 2 and 3, said Dr. Mark S. Sulkowski of Johns Hopkins University, Baltimore, and his associates ((N. Engl. J. Med. 2014 Jan. 16;370:211-21).
Courtesy U.S. Department of Veterans Affairs
The once-daily oral treatment was effective against HCV type 1 among patients with any viral subtype, as well as among patients who had failed to respond to or had developed resistance to protease inhibitors.
In particular, the daclatasvir-sofosbuvir combination was very effective in patients "with characteristics that were previously associated with a poor response to treatment – HCV genotypes 1a and 3, the non-CC IL28B genotype, and black race," the investigators noted.
Dr. Sulkowski and his colleagues assessed the combination therapy in an open-label study involving 211 adults treated during a 17-month period at 18 medical centers across the United States.
Initially, 44 previously untreated patients with HCV 1 infection and 44 patients with HCV 2 or 3 were randomly assigned to receive daclatasvir plus sofosbuvir, with or without concurrent ribavirin, for 24 weeks. Then the study was expanded to include another 123 patients with HCV 1 infection: 82 who were previously untreated were randomly assigned to receive the combination therapy, with or without ribavirin, for 12 weeks; and the remaining 41 who had failed on telaprevir or boceprevir plus peginterferon alfa-ribavirin were assigned to receive the combination therapy, with or without ribavirin, for 24 weeks.
The primary efficacy endpoint was a sustained virologic response (defined as an HCV RNA level of less than 25 IU/mL) at week 12 after the end of treatment.
That rate was 98% (164 of 167 patients) among those who had HCV 1 infection. Of the three patients in that group classified as not having a sustained virologic response at week 12, two missed their assessment visit at 12 weeks but showed a sustained virologic response at 24 weeks, and the third was lost to follow-up.
The rate of sustained virologic response was 91% (40 of 44 patients) among those who had HCV 2 or 3 infection. Individually, the rate was 92% in patients with HCV 2 and 89% among those with HCV 3, the investigators said.
Dr. Mark S. Sulkowski
The high rates of sustained virologic response were consistent across all subgroups of patients, including 129 of the 132 (98%) who had genotype 1a; 57 of the 61 (93%) who had genotype IL28B; 25 of the 26 (96%) who were black; 9 of the 10 (90%) who were of "other" race/ethnicity; 85 of the 90 (94%) who received concurrent ribavirin; 119 of the 121 (98%) who did not receive ribavirin; and 40 of the 41 (98%) who had failed on or developed resistance to protease inhibitors.
"This represents proof of concept that a sustained virologic response can be achieved in patients in whom previous treatment with telaprevir or boceprevir had failed, including patients who have persistent HCV variants with resistance to protease inhibitors," Dr. Sulkowski and his associates said.
Two patients discontinued treatment because of adverse events. One patient developed fibromyalgia, and another had a stroke. Both had shown a sustained virologic response to the combination therapy. The most common adverse events were fatigue, headache, and nausea. The most common grade 3 or 4 laboratory abnormalities were low phosphorous levels and elevated glucose levels.
The study was supported by Bristol-Myers Squibb and Pharmasset (now Gilead). Dr. Sulkowski reported financial ties to Bristol-Myers Squibb and Gilead, in addition to other pharmaceutical companies. His associates reported ties to numerous industry sources.