Published: Mar 4, 2014
By Ed Susman , Contributing Writer, MedPage Today
BOSTON -- An all-oral, 12-week regimen appears to successfully treat hepatitis C virus (HCV) infection in about 90% of patients, researchers reported here.
Of the 166 treatment-naive patients in the study, 92% achieved a sustained virologic response at 12 weeks (SVR-12) on the combination of the investigative NS5A inhibitor daclatasvir, the protease inhibitor asunaprevir and the non-nucleoside BMS-791325, said Trevor Hawkins, MD, chief medical officer at Southwest CARE Center and professor of medicine at the University of New Mexico in Santa Fe.
"The observed analysis showed a 92% SVR12, and in the modified intent-to-treat analysis -- wherein data at week 12 is counted as failure if it is missing -- [it] was 89%," Hawkins toldMedPage Today at the annual Conference on Retroviruses and Opportunistic Infections.
A cure in the context of HCV is a sustained virologic response (SVR) -- defined as undetectable viral RNA at some prespecified point after ending therapy, usually 12 or 24 weeks.
At the end of treatment in Hawkins' study, 97.5% of those in the low-dose BMS-971325 group showed a complete viral response compared with 94.2% of those taking the high dose; the SVR4 was 92.4% in the low-dose group and 91.7% in the high-dose-treated patients. The SVR12was achieved by 92.2% in the low-dose treatment group and by 91.7% of those taking high-dose BMS-791325, the researchers reported.
In the trial, Hawkins said that 9% of the patients were diagnosed with cirrhosis. He said that there did not appear to be a difference in outcome among the cirrhotic patients compared with those who were not cirrhotic -- 13 of the 15 cirrhotic patients achieved an SVR12.
Hawkins said that the next trials -- called UNITY 1 and UNITY 2 -- will separate cirrhotic and noncirrhotic patients to examine if there are differences in outcomes depending on the extent of liver disease. These trials will use the 75-mg dose of BMS-791325.
The trial he reported here showed that patients were able to tolerate the regimen. "There were two discontinuations due to adverse events in the entire 166-patient cohort," he said at a press conference.
The patients diagnosed with HCV genotype 1 were randomly assigned to receive a twice-daily regimen of daclatasvir 30 mg, asunaprevir 200 mg and BMS-791325 at 75 mg or 150 mg for 12 weeks. Hawkins said outcomes were similar for the 80 patients on BMS-791325 given 75 mg twice daily and the 86 patients given BMS-791325 at a dose of 150 mg twice daily.
"There were 11 virologic failures and we attempted to find out if there were any predictors of failure," he said. "The only thing that appeared to predict failure was being of genotype 1a. We tried to determine if there were any polymorphisms at baseline that would predict virologic failure, but we were unable to do that. There really was no obvious correlation."
In pilot studies, the 24-week SVR was 94% and the 12-week SVR was 94% with use of the 75-mg dose of BMS-791325; with the 150-mg dose, the 24-week SVR was 94% and the 12- week SVR was 89%.
The patients were about 54 years old, 67% were men, 83% were white, 82% were genotype 1a, and 15 patients in the study -- 9% -- were diagnosed with cirrhosis.
"This looks good," press conference moderator Jean-Michel Pawlotsky, MD, of the Hôpital Henri Mondor Creteil/University of Paris-Est, told MedPage Today. "There are several potential combinations that are going to work in patients with HCV. This combination with three drugs has good potency and a high barrier to resistance. This is promising."
The study was sponsored by Bristol-Myers Squibb.
Hawkins disclosed commercial interests with Gilead, Janssen, AbbVie, Bristol-Myers Squibb, BMS, Vertex, GlaxoSmithKline, Sangamo, Salix, Merck and ViiV. Co-authors include Bristol-Myers Squibb employees.
Pawlotsky had no disclosures.