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news.Roche, InterMune, a biotechnology company, and Pharmasset have reported the first results from their interferon-free regimen of direct acting antiviral combination therapy for the treatment of patients chronically infected with the hepatitis C virus.
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The study combined two oral DAAs, R7227 and R7128, for the first time in patients. There were no serious adverse events reported during the 14 days of dosing, and the reductions in levels of hepatitis C virus (HCV) RNA were significant, the three companies said.
The trial, conducted in centers in New Zealand and Australia, is the first to investigate the combination of two oral antiviral medicines in the absence of interferon and ribavirin. The results demonstrated for the first time that the combination of an oral protease inhibitor and an oral nucleoside polymerase inhibitor resulted in significant HCV viral load reduction in patients with HCV. Roche is developing R7227, a protease inhibitor, with InterMune, and R7128, a nucleoside polymerase inhibitor, with Pharmasset.
Inform-1 is a randomized, double-blind, ascending dose Phase I trial which has enrolled a total of 57 patients. Patients receiving the combination of R7227 and R7128 for 14 days – without pegylated interferon or ribavirin – experienced a median reduction in viral levels of -4.8 to -5.2log(10)IU/ml in the highest doses tested.
The addition of R7128 to R7227 resulted in sustained viral load reductions over the dosing period, with approximately 63% of patients experiencing a decrease in viral levels below the quantification limit of the diagnostic assay (less than 40IU/ml). Furthermore, 25% of patients in the highest dosage groups were below the limit of detection of the virus in their blood (less than 15IU/ml) after 14 days.
In the early low-dose groups, after only three days of dosing, the mean reduction in viral load levels was 0.6log(10)IU/ml greater with combination treatment (-2.9), compared to the performance of the individual compounds when administered as a single agent (-0.46 and -1.84 for R7128 and R7227, respectively). This suggests an additive effect for the combination. Pharmacokinetic analysis confirmed that there were no drug-drug interactions between the compounds.
The companies are now exploring twice-daily dosing of R7227 and higher total daily doses (600mg twice-daily and 900mg twice-daily) than those explored in the first patient cohorts of Inform-1. The companies also plan to explore the innovative direct acting antiviral (DAA) combination therapy in ‘treatment-experienced’ patients with HCV, or those who did not achieve sustained viral response with a previous interferon-based treatment.