Ground-Breaking Combination of All-Oral Agents Demonstrates Potential as Hepatitis C Treatment Regimen
- Combination of R7227, protease inhibitor, and R7128, nucleoside polymerase inhibitor, shows significant potency in reducing viral load in patients with hepatitis C - NUTLEY, N.J., BRISBANE, Calif., and PRINCETON, N.J., April 25 /PRNewswire-FirstCall -- Roche, InterMune, Inc. (Nasdaq: ITMN) and Pharmasset (Nasdaq: VRUS) today announced the first results from their innovative, interferon-free regimen of direct acting antiviral (DAA) combination therapy for the treatment of patients chronically infected with the hepatitis C virus (HCV)(1). The study combined two oral DAAs, R7227 (also known as ITMN-191) 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 HCV RNA were significant.
Results of the INFORM-1 study were presented today during the late-breaker session at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL) in Copenhagen.
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.
Further studies will test the activity and safety of the combination of R7227 and R7128 with and without interferon and/or ribavirin. The current standard of care for HCV is a combination of pegylated interferon plus ribavirin, which delivers overall sustained virologic response rates (SVR) of 50-60 percent.
"These are exciting times in our fight against hepatitis C, and the investigation of the innovative oral treatment regimen in INFORM-1, if validated in further study, may radically change future treatment strategies in our patients with chronic HCV infection," said Edward Gane, M.D., Associate Professor, University of Auckland and Director, Auckland Clinical Studies Limited. "The initial results from this study of the R7227/R7128 combination raise hopes of the possibility for an interferon-free treatment regimen, as well as the potential for a shorter, more potent interferon-based regimen."
INFORM-1 Results in Brief
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 -5.2 log(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 aproximately 63 percent of patients experiencing a decrease in viral levels below the quantification limit of the diagnostic assay (less than 40 IU/mL). Furthermore, 25 percent of patients in the highest dosage groups were below the limit of detection of the virus in their blood (less than 15 IU/mL) after 14 days.
- Combination of R7227, protease inhibitor, and R7128, nucleoside polymerase inhibitor, shows significant potency in reducing viral load in patients with hepatitis C - NUTLEY, N.J., BRISBANE, Calif., and PRINCETON, N.J., April 25 /PRNewswire-FirstCall -- In the early low-dose groups, after only three days of dosing, the mean reduction in viral load levels was 0.6 log(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.
No treatment-related serious adverse events (SAEs), no dose reductions and no discontinuations were reported in the study. Pharmacokinetic analysis confirmed that there were no drug-drug interactions between the compounds.
Next Steps in the Development Program
The companies are now exploring twice-daily dosing of R7227 and higher total daily doses (600 mg twice-daily and 900 mg twice-daily) than those explored in the first patient cohorts of INFORM-1. The companies also plan to explore the innovative DAA combination therapy in "treatment-experienced" patients with HCV, or those who did not achieve SVR with a previous interferon-based treatment.
Other Clinical Studies with R7227 and R7128
In addition to clinical studies of combination DAA regimens such as those studied in INFORM-1, R7227 and R7128 each are proceeding rapidly in development in combination with Roche's PEGASYS(R) (peginterferon alfa-2a) and COPEGUS(R) (ribavirin). A Phase IIb study with R7128 has now begun, while a Phase IIb study with R7227 is slated to begin in the summer.