WELWYN GARDEN CITY, England, April 27 /PRNewswire/ --
- Phase II Study Demonstrates Impressive End-of Treatment Response - Providing Future Hope for Patients
Roche's investigational treatment for hepatitis C, R1626, has shown an impressive end-of-treatment response rate when given in combination with the current standard of care, pegylated interferon and ribivarin. R1626 belongs to a new class of oral antivirals called polymerase inhibitors that directly targets the hepatitis C virus and inhibits its replication. It is hoped that this innovative combination will increase the number of patients who manage to clear the hepatitis C virus, thereby curing them of a disease that can lead to liver cirrhosis, cancer and death.
Results from the phase II study show that levels of the hepatitis C virus (HCV) were undetectable in 84% of patients infected with genotype 1 virus (the most difficult to treat) when patients were treated for 4 weeks with this triple combination, followed by 44 weeks of Pegasys (peginterferon alfa-2a) and Copegus (ribavirin). This was significantly higher than in patients treated with peginterferon alfa-2a and ribavirin alone for the entire 48-week treatment period (65%).(1) These new data were presented in a late-breaker oral session at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL), currently being held in Milan, Italy.
"These results demonstrate that R1626 holds significant promise to potentially increase the number of hepatitis C patients who can be successfully treated. It is particularly interesting that R1626, a polymerase inhibitor, is demonstrating a higher end-of-treatment response rate than current HCV protease inhibitors in development, together with a high barrier to the development of resistance," said Dr David Nelson, Director of Hepatology and Liver Transplantation at the University of Florida, Gainesville, Florida, USA. "Since most patients responded very early in treatment with R1626, we expect excellent SVR rates (indicative of a cure) that improve significantly on those achieved with the current standard of care. I look forward to SVR data from this Phase IIa study, and to results of the ongoing Phase IIb study."
Patients in this Phase IIa study will be followed for an additional 24 weeks with no treatment to determine the rate of sustained virological response (SVR), indicating a cure.
Hepatitis C, one of the most common chronic blood-borne infections, is transmitted primarily through blood or blood products. Estimates of prevalence for hepatitis C in England and Wales vary considerably from 200,000 to 500,000. It is a leading cause of cirrhosis, liver cancer and liver failure, despite being potentially curable. The future of hepatitis C therapy is likely to involve combinations of new small-molecule antiviral drugs and pegylated interferon-based treatment, like Pegasys.
More About the Phase IIa Study and End-of-Treatment Results Presented at EASL
The Phase IIa study is a multicenter trial that enrolled 104 patients with genotype 1 HCV, who had not previously received treatment. Its primary endpoint was to evaluate the 4-week efficacy and safety of combining R1626 with Pegasys alone or with Pegasys (peginterferon alfa-2a) plus Copegus (ribavirin), in comparison to a current HCV standard of care, Pegasys plus Copegus.
Patients were randomised into the following treatment groups:
- Group A: R1626 1,500 mg twice a day plus peginterferon alfa-2a 180 mcg weekly for 4 weeks
- Group B: R1626 3,000 mg twice a day plus peginterferon alfa-2a 180 mcg weekly for 4 weeks
- Group C: R1626 1,500 mg twice a day plus peginterferon alfa-2a180 mcg weekly plus ribavirin 1,000/1,200 mg daily for 4 weeks
- Group D (standard of care group): peginterferon alfa-2a 180 mcg weekly plus ribavirin 1,000/1,200 mg daily for 4 weeks
Following the 4 weeks of treatment in this study, all patients received peginterferon alfa-2a 180 mcg weekly plus ribavirin 1,000/1,200 mg daily for an additional 44 weeks to complete the 48-week trial.
The study found(1):
- Data collected at 4 weeks showed that patients receiving the triple combination (Group C) had a mean decrease in viral load of 5.2 log10 from baseline, indicating a robust and rapid virological response
- At week 48, HCV was undetectable in 84% of patients receiving the triple combination R1626 1,500 mg BID + peginterferon alfa-2a + ribavirin, compared with 65% of patients treated with peginterferon alfa-2a and ribavirin alone
Side Effect Profile:
- A higher incidence of grade 4 neutropenia was reported in the R1626 treatment arms during the 4-week treatment period; however, after stopping treatment with R1626, absolute neutrophil counts returned to the levels typically seen with patients taking standard of care alone
R1626 - a High Barrier to the Development of Resistance
In a separate oral presentation at EASL, it was reported that R1626 continues to present a high barrier to the development of viral resistance. Resistance is emerging as a serious concern in hepatitis C treatment, as resistant viruses have emerged in patients early on in treatment with protease inhibitors. Resistance to R1626, a polymerase inhibitor, has not been yet been identified, after either 2 weeks of R1626 monotherapy, or after 4 weeks in patients treated with R1626 in combination therapy.(2)
R1626 is not licensed for the treatment of hepatitis C
About Roche in the UK
Roche aims to improve people's health and quality of life with innovative products and services for the early detection, prevention, diagnosis and treatment of disease. Part of one of the world's leading healthcare groups, Roche in the UK employs nearly 2,000 people in pharmaceuticals and diagnostics. Globally Roche is the leader in diagnostics, and a major supplier of medicines for the treatment of cancer, transplantation, virology, bone and rheumatology, obesity and renal anaemia. Find out more at http://www.rocheuk.com
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References:
(1). Nelson D, Pockros P, Godofsky E, et al. 84% end-of-treatment response (EOTR, week 48) achieved with R1626, peginterferon alfa 2a (40KD) and ribavirin for 4 weeks followed by the standard of care: Results of a phase 2a study in treatment-naive HCV genotype 1 patients. In: 43rd Annual Meeting of the European Association for the Study of the Liver (EASL); 2008 April 26, 2008; Milan, Italy; 2008.
(2). Le Pogam S, Seshaadri A, Kang H, et al. Low level of resistance, low viral fitness and absence of resistance mutations in baseline quasispecies may contribute to high barrier to R1626 resistance in vivo. In: 43rd Annual Meeting of the European Association for the Study of the Liver (EASL); 2008; Milan, Italy; 2008.
Contact: Olivia Garbutt, Roche, +44(0)1707-367842, Holly Brafman, Weber Shandwick, +44(0)207-067-0184
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