Roche's R1626, First-in-Class Hepatitis C Polymerase Inhibitor, Demonstrates Impressive End-of-Treatment Response in Phase IIa Study
BASEL, Switzerland, April 26/PRNewswire/ --
- R1626 Also Shows a High Barrier to the Development of Resistance
Roche's investigational treatment for hepatitis C, R1626, has shown an
impressive end-of-treatment response rate when given in combination with
PEGASYS(R) (peginterferon alfa-2a) and COPEGUS(R) (ribavirin).
After 4 weeks of treatment with this triple combination, followed by 44
weeks of Pegasys and Copegus, levels of the hepatitis C virus (HCV) were
undetectable in 84% of patients infected with genotype 1 virus. This was
higher than in patients treated with Pegasys and Copegus 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), being held in Milan, Italy.
Discovered and developed at Roche, R1626 is a potent polymerase inhibitor
which belongs to a new generation of treatments that directly inhibit
replication of HCV. It is the most advanced polymerase inhibitor in
development.
"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 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.
Rapid development of R1626 - a Large Phase IIb Study is Now Fully
Enrolled
A large Phase IIb study with R1626 was initiated in November 2007 to
define the optimal dose of R1626, in combination with Pegasys and Copegus.
This Phase IIb trial, called POLI 1, is now fully enrolled with approximately
500 patients.
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 plus Copegus, 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 Pegasys 180 mcg weekly for 4
weeks
- Group B: R1626 3,000 mg twice a day plus Pegasys 180 mcg weekly for 4
weeks
- Group C: R1626 1,500 mg twice a day plus Pegasys 180 mcg weekly plus
Copegus 1,000/1,200 mg daily for 4 weeks
- Group D (standard of care group): Pegasys 180 mcg weekly plus Copegus
1,000/1,200 mg daily for 4 weeks
Following the 4 weeks of treatment in this study, all patients received
Pegasys 180 mcg weekly plus Copegus 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 + Pegasys + Copegus, compared with
65% of patients treated with Pegasys and Copegus alone
- A higher incidence of grade 4 neutropaenia 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 a serious concern in hepatitis C treatment, as resistant
viruses have emerged in patients early on in treatment with protease
inhibitors. Resistance to R1626 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)
About Hepatitis C
Hepatitis C, the most common chronic blood-borne infection, is
transmitted primarily through blood or blood products. Hepatitis C
chronically infects 180 million people worldwide, with an additional three to
four million people newly infected each year.(3) 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, such
as Pegasys.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading
research-focused healthcare groups in the fields of pharmaceuticals and
diagnostics. As the world's biggest biotech company and an innovator of
products and services for the early detection, prevention, diagnosis and
treatment of diseases, the Group contributes on a broad range of fronts to
improving people's health and quality of life. Roche is the world leader in
in-vitro diagnostics and drugs for cancer and transplantation, a market
leader in virology and active in other major therapeutic areas such as
autoimmune diseases, inflammation, metabolic disorders and diseases of the
central nervous system. In 2007 sales by the Pharmaceuticals Division
totalled 36.8 billion Swiss francs, and the Diagnostics Division posted sales
of 9.3 billion Swiss francs. Roche has R&D agreements and strategic alliances
with numerous partners, including majority ownership interests in Genentech
and Chugai, and invested over 8 billion Swiss francs in R&D in 2007.
Worldwide, the Group employs about 79,000 people. Additional information is
available on the Internet at http://www.roche.com.
All trademarks used or mentioned in this release are protected by law.
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.
(3). World Health Organization. Initiative for Vaccine Research, Viral
Cancers, Hepatitis C. 2006. (Accessed July 24, 2006, at
http://www.who.int/vaccine_research/diseases/viral_cancers/en/index2.html.)
Source: Roche
Contact: Mike Nelson, Roche, +41-79-572-5165, Michelle Marchione, Axon Communications, +44(0)208-439-9449
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