Drug & Device Development

Danoprevir enhances sustained HCV response rates

Last Updated: 2013-07-12 17:02:23 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Danoprevir with interferon and ribavirin produced high sustained viral response rates (SVR) in patients with hepatitis C virus (HCV)-1, in a multinational phase II trial.

Researchers say 237 treatment-na�ve patients with HCV-1 were randomly assigned to receive peginterferon alfa-2a/ribavirin with danoprevir or placebo for 12 weeks, and ultimately, 225 received at least one dose of study drug.

After the first week of treatment, HCV RNA fell by an average of 3.95 to 4.28 log10 IU/mL with various doses of danoprevir, compared with a 0.77 log10 IU/mL decrease in the placebo group, according to Dr. Patrick Marcellin from Hopital Beaujon, Clichy, France, and colleagues.

Patients in the danoprevir group achieved maximum reductions in HCV RNA after four to six weeks of treatment, and they sustained these reductions throughout the first 24 weeks of treatment. In contrast, placebo patients did not achieve maximum reductions in HCV RNA until week 20.

The proportion of danoprevir-treated patients with a rapid virological response was 74% in the 300-mg group, 88% in the 600-mg group, and 86% in the 900-mg group, compared with 7% in the placebo group.

SVR rates with danoprevir were 68% with 300 mg, 85% with 600 mg, and 76% with 900 mg, compared with 42% with placebo.

Relapse rates were higher with placebo (38%) than with danoprevir (18% with 300 mg, 8% with 600 mg, 11% with 900 mg).

Only three patients (1.4%) had detectable danoprevir resistance mutations at baseline, and all three achieved undetectable HCV RNA at week 12. Two of these patients achieved SVR, and one relapsed, the research team reported online June 28 in Gastroenterology.

Another eight patients (4%) developed viral resistance-related breakthrough or partial response during danoprevir therapy, whereas five patients (4%) had viral breakthrough during therapy in the placebo group.

Adverse events generally followed a similar pattern in the danoprevir and placebo groups, but four danoprevir patients had transient, dose-related, grade 4 elevations in alanine aminotransferase (three in the 900-mg group and one in the 600-mg group). ALT returned to pre-elevation levels 15-25 days after danoprevir was stopped.

Serious adverse events affected 7-8% of the danoprevir groups, compared with 19% of patients in the placebo group.

"Recognizing the high potency of danoprevir, but desiring an improved pharmacokinetic profile, a ritonavir-boosted formulation of danoprevir has been developed for subsequent clinical studies," the researchers say in their paper. "Interim efficacy and safety data recently reported for the combination of ritonavir-boosted danoprevir plus peginterferon alfa-2a/ribavirin in treatment-na�ve patients with HCV genotype 1 or 4 infection in the DAUPHINE study are promising."

According to its website, Roche expects to file the New Drug Application for danoprevir in 2016.

Funding for the study came from Roche/Genentech, which employed 11 of the 22 authors and had various relationships with the other 11 authors.

The authors did not respond to a request for comment.

SOURCE: http://bit.ly/12tecnJ

Gastroenterol 2013.