Roche's Pol Inhib R1626

[drofi]

http://tinyurl.com/3cthcw

November 2, 2007 -- Boston  
Roche’s Investigational Polymerase Inhibitor, Combined with PEGASYS® and COPEGUS™, Shows Potent Antiviral Activity in Treatment of Chronic Hepatitis C at Four Weeks
  
--Roche progresses R1626 into phase IIb study, called POLI 1--
  
R1626, one of Roche’s new investigational drugs for chronic hepatitis C virus (HCV) infection, has shown promising antiviral activity when given in combination with PEGASYS® (peginterferon alfa-2a) and COPEGUS™ (ribavirin), according to results being presented at the American Association for the Study of the Liver Disease (AASLD) meeting, being held in Boston, Nov. 2-6.  After four weeks of treatment with this triple combination, the virus could no longer be detected in up to 81 percent of patients, with a mean decrease in viral load of 5.2 log10 from baseline.  This is indicative of a robust virological response, and R1626 is being progressed into Phase IIb study as a result of these findings.
R1626 belongs to a class of antivirals called polymerase inhibitors, which are being investigated in combination with the current standard of care, pegylated interferon and ribavirin.  The hope is that this combination will increase the number of patients who are able to be successfully treated for hepatitis C.
“The results from this Phase IIa study show that R1626 has a profound antiviral effect when used in combination with PEGASYS plus COPEGUS,” said Dr. Paul Pockros, Scripps Clinic, San Diego, California, the lead investigator of the study.  “This effect of R1626 in combination therapy, along with the lack of resistance observed to date, means that R1626 could be an exciting drug for patients with hepatitis C, if a safe and acceptable dosing regimen can be determined in future studies.”
Antiviral Activity and Safety Results Being Presented at AASLD
The multicenter Phase IIa study enrolled patients with genotype 1 chronic HCV who have not previously received treatment.  The objectives were to evaluate the four-week activity and safety of combining R1626 with PEGASYS alone or R1626 with PEGASYS plus COPEGUS in comparison to PEGASYS/COPEGUS, the standard of care.  The study found:
·                    Up to 81 percent of those patients treated with R1626 1500 mg (twice-daily) + PEGASYS + COPEGUS had an undetectable HCV viral load by week four (mean reduction of 5.2 log10 IU/mL)
·                    ALT, a liver enzyme, normalized in approximately 50 percent of patients in R1626 treatment groups
·                    Most reported adverse events were mild to moderate.  Dose dependent, reversible grade four neutropenia was observed in the R1626 arms (36 percent in patients receiving R1626 1500 mg + PEGASYS + COPEGUS), and was the main reason for dose reduction and discontinuation
Lack of Resistance
According to a second presentation at the conference, resistance to R1626 was not identified following intensive testing for either two weeks of treatment with R1626 as monotherapy, or in patients treated with R1626 for four weeks in combination with the standard of care.  These findings suggest that there is a high barrier to the development of resistance to R1626 in vivo.
Start of Phase IIb Trial
R1626 is being progressed into Phase IIb study, called POLI 1, to further investigate the new treatment regimens of R1626, in combination with standard or lower dose of PEGASYS and standard dose of COPEGUS.  This Phase IIb trial is now open and enrolling patients in eight countries, including the United States.  More information about R1626 and the clinical studies can be found on www.roche-trials.com.
“As a clinician, I am excited by the high rates of viral negativity that were observed after four weeks of treatment with R1626 in combination with the standard of care.  The design of the Phase IIb study should enable us to find the doses of R1626, PEGASYS and COPEGUS that achieve the appropriate balance between safety and efficacy,” said Dr. David Nelson, Director of Hepatology and Liver Transplantation at the University of Florida, Gainesville, and a lead investigator in this Phase IIb study.

[3txsofar]

I would and should have stated that I'd be overjoyed with a polymerase inhibitor being successful.  

I have though been thoroughly dissapointed in so many of the company PRs and the 'journalist' coverage of the AASLD, that rather than just get upset, I have taken the time to analyze and point out the deficiencies.

Cheers!

[drofi]

sure, there are not enough facts. However, I think the future of HCV-treatment will be a combo of different substances to avoid resistance against single substances and to keep the pressure on the vampire for enough weeks. We have seen great success in HIV treatment with this strategy and there is little doubt  this strategy will work for HCV too, and even better. Hence I am happy for any new development which is a polymerase inhibitor, and no protease inhibitor. There are two promissing Prot-I already (e.g. Telaprevir), but no promissing POL-IT like R1626 so far. Nice to read that there were no resistant clones aftre monotherapy by R1626.
The question is just, do you have enough time to see the golden future of STAT? http://tinyurl.com/2ye4lv

[3txsofar]

Unfortunately, this is more of a PR puff piece, than real info.  It sys that most "adverse events were mild to moderate".  It does go on to say that neutropenia was the main cause of discontinuation, but it doesn't give how many discontinued.  Vertex reported that the median date for discontinuation was 64 days, so since Roche is only at 28 days, one could expect many more discontinuations.

Also, it is very interesting that Roche owns the main viral load test for HCV, yet in this piece they do not give at what level they measures the virus.  They say that 81% are undetected, but not at what level.  When Vertex reported 4 week RVR at EASL they gave it both as under 30 IU/ml and under 10, with the rates being 88% and 79 % respectively.  So, why doesn't Roche even say at what level they measured?