WCTF.org Transplant News

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

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.

Source: Roche UK

Contact: Olivia Garbutt, Roche, +44(0)1707-367842, Holly Brafman, Weber Shandwick, +44(0)207-067-0184

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