Biotech Values

[DewDiligence]

Roche's R1626 Demonstrated Significant End-of-Treatment Response in Phase-2a Study

http://biz.yahoo.com/prnews/080426/nysa001.html

>>
Saturday April 26, 12:15 pm ET

- 84 percent of patients had undetectable levels of HCV at end of treatment -

MILAN, Italy, April 26 /PRNewswire/ -- Roche's investigational therapy for chronic hepatitis C virus (HCV) infection, R1626, has shown a significant end-of-treatment response rate when given in combination with PEGASYS® (peginterferon alfa-2a) and COPEGUS® (ribavirin). R1626 also shows a high barrier to the development of resistance.

After four weeks of treatment with this triple combination, followed by 44 weeks of PEGASYS and COPEGUS, levels of HCV were undetectable in 84 percent of patients infected with genotype 1 virus. This was higher than patients treated with PEGASYS and COPEGUS alone for the entire 48-week treatment period (65 percent). 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.

R1626 was discovered and developed at Roche and belongs to a class of antivirals called polymerase inhibitors, which are being investigated with the current standard of care for hepatitis C combination therapy with pegylated interferon and ribavirin.

"These results demonstrate that R1626 holds significant promise to potentially increase the number of hepatitis C patients who can be successfully treated," said Dr. David Nelson, Director of Hepatology and Liver Transplantation at the University of Florida, Gainesville, Florida. "Since most patients responded very early in treatment with R1626, we expect sustained virological response (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 SVR rate, which indicates successful treatment.

More About the Phase IIa Study and End-of-Treatment Results

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 four-week efficacy and safety of combining R1626 with PEGASYS alone or with PEGASYS plus COPEGUS, in comparison to a current HCV standard of care (SOC), pegylated interferon plus ribavirin.

Patients were randomized into the following treatment groups:

* Group A: R1626 1,500 mg twice a day plus PEGASYS 180 mcg weekly for four weeks

* Group B: R1626 3,000 mg twice a day plus PEGASYS 180 mcg weekly for four weeks

* Group C: R1626 1,500 mg twice a day plus PEGASYS 180 mcg weekly plus COPEGUS 1,000/1,200 mg daily for four weeks

* Group D (standard of care group): PEGASYS 180 mcg weekly plus COPEGUS 1,000/1,200 mg daily for four weeks

Following the four 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:

* Data collected at four 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 percent of patients (26 of 31) who received the triple combination of R1626 1,500 mg BID + PEGASYS + COPEGUS compared with 65 percent of patients (13 of 20) treated with the SOC.

* A higher incidence of grade four neutropenia was reported in the R1626 treatment arms during the four-week treatment period; however, after stopping treatment with R1626, absolute neutrophil counts returned to the level typically seen with patients receiving the SOC 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. This is a serious concern emerging in the development of small molecule treatments for hepatitis C. Resistance to R1626 has not been yet been identified, after either two weeks of R1626 monotherapy, or after four weeks in patients treated with R1626 in combination therapy.

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, all with genotype 1 hepatitis C.
<<