Early clinical data on the hepatitis
C polymerase inhibitor R1626, currently in development by Roche Laboratories,
show viral reductions greater than those described for other polymerase inhibitors,
according to data presented at the 57th Annual Meeting of the American Association
for the Study of Liver Diseases (AASLD) in Boston last month.
These Phase
I results were observed in chronic hepatitis C patients infected with difficult-to-treat
genotype 1 virus, and "suggest that R1626 holds significant promise for the
treatment of hepatitis C," according to lead investigator Stuart Roberts,
MD, Director of Gastroenterology at Alfred Hospital in Melbourne, Australia. "Adding
R1626 to the current therapies could potentially improve treatment success rates
in hepatitis C."
About the Study
In this Phase I study,
47 patients with genotype 1 HCV were randomly assigned to receive either oral
R1626 twice daily (500, 1500, 3000, or 4500 mg twice daily) or placebo for 14
days. The final results presented at AASLD included patients who received the
2 higher doses of R1626.
Results
Clinically significant mean reductions in serum HCV RNA of 2.64 and 3.47 log,
respectively, were observed with R1626 at the 3000 mg and 4500 mg doses.
R1626 demonstrated good tolerability following dosing for 14 days up to 3000 mg
twice daily; no patients withdrew prematurely from the study.
Increasing numbers of adverse events were noted at higher dose levels.
Reversible mild to moderate hematological changes were observed with increasing
doses.
Based
on these results, Roche has already commenced a Phase II trial to evaluate how
well R1626 works in combination with Pegasys (pegylated interferon alfa-2a) and
ribavirin.
"The
development of R1626, ongoing research with Pegasys, and partnerships with Intermune,
Pharmasset, and Maxygen underscore Roche's long-term commitment to finding effective
therapies to benefit patients with chronic hepatitis C," said Nick Cammack,
Head of Viral Diseases Research for Roche.
About
the Phase II Study (PV18369)
PV18369
is an ongoing multicenter Phase
II trial that is enrolling patients with genotype 1 chronic hepatitis C who
have not previously received treatment.
Patients
are randomized into 4 treatment groups assessing R1626 with Pegasys or with Pegasys/ribavirin,
versus the standard of care (Pegasys plus ribavirin).
Following
the first 4 weeks of treatment, all patients will receive Pegasys 180 mcg by subcutaneous
injection once weekly plus ribavirin 1000-1200mg daily for another 44 weeks, for
a total treatment duration of 48 weeks.
The
primary objectives of the study are to evaluate the 4-week safety and antiviral
effect of combining R1626 with Pegasys with or without ribavirin. The study is
currently enrolling patients in the U.S. Patients will be randomly assigned to
4 treatment arms:
Group A: R1626 1500 mg twice daily + 180 mcg Pegasys subcutaneous injection
every week for 4 weeks;
Group B: R1626 3000 mg twice daily + 180
mcg Pegasys every week for 4 weeks;
Group C: R1626 1500 mg twice
daily + 180 mcg Pegasys every week + ribavirin 1000-1200 mg daily for 4 weeks;
Group D: 180 mcg Pegasys + ribavirin 1000-1200 mg daily (standard
of care group) for 4 weeks.
Patients
and healthcare providers interested in the trial can find more information at
www.roche-trials.com
Department
of Gastroenterology, Alfred Hospital, Melbourne, VIC, Australia; Royal Brisbane
Hospital, Brisbane, QLD, Australia; St. Vincents Hospital, Darlinghurst, NSW,
Australia; Christchurch Clinical Studies Trust, Christchurch, New Zealand; Infectious
Disease Unit , Royal Adelaide Hospital, Adelaide , SA, Australia; Hoffman-La Roche
Ltd, Palo Alto, CA & Nutley, NJ.
11/10/06
References
S
Roberts, G Cooksley, G Dore, and others. Results of a Phase 1B, Multiple Dose
Study of R1626, a Novel Nucleoside Analog Targeting HCV Polymerase in Chronic
HCV Genotype 1 Patients. 57th AASLD. Boston, MA. October 27-31, 2006. Abstract
LB2.
Roche Laboratories.
Roche Oral Polymerase Inhibitor R1626 Shows Strong Antiviral Activity in Chronic
Hepatitis C Patients in Early Trial. Press Release. October 27, 2006.
Clinically significant mean reductions in serum HCV RNA of 2.64 and 3.47 log,
respectively, were observed with R1626 at the 3000 mg and 4500 mg doses.
