Submitted by Armen Hareyan on Dec 4th, 2007
MIGENIX has received preliminary four-week interim results from a Phase II viral kinetics study in hepatitis C virus treatment-naive patients which indicate that celgosivir (an oral alpha glucosidase I inhibitor) has no negative effects on the tolerability, pharmacokinetics and viral kinetics when combined with the standard of care drugs, pegylated interferon plus ribavirin, as compared to the standard of care drugs alone.
The interim results include 10 patients who had completed 4-weeks of treatment equally divided between: (i) pegylated interferon (alfa-2b) plus ribavirin ("PR"); and (ii) celgosivir 400mg QD plus PR ("PRC"). The results are interim as the study is designed as a 20-patient, 12-week study. The following is a summary of the preliminary interim four-week results:
- viral kinetics in both treatment groups are similar with a median reduction in HCV RNA at 4 weeks of 3.5 log(10) vs 3.8 log(10) in the PRC and PR groups, respectively. The variability of response is wide with reductions of 5.4 log(10) to 0.8 log(10) and 4.5 log(10) to 2.5 log(10) for the PRC and PR groups, respectively. Virus was undetectable in one patient who was in the PRC group (none in the PR group).
- PRC treatment was well tolerated, with both the PRC and PR groups demonstrating similar tolerability, which is consistent with observations from prior studies. Gastrointestinal tolerability of the PRC treatment was slightly better in this study compared to prior studies. No serious adverse events were reported.
Due to the small number of patients and the high response rate with standard of care alone, any conclusion about differences in efficacy between the groups is speculative at this point. The Company will be completing a thorough analysis of the data from this trial, along with data from an extension protocol with patients continuing from a previous Phase II non-responder study (see summary of the non-responder study results below), to determine the next steps in the development of celgosivir. An update will be provided as part of the Company's quarterly news release and conference call on December 13th, 2007.
About Celgosivir (MX-3253)
Celgosivir, an oral inhibitor of alpha-glucosidase I, is currently the only anti-HCV drug in clinical development that acts on host-directed glycosylation. In preclinical studies, celgosivir has shown excellent in vitro synergy with various interferons in the clinic or in development including Pegasys, PEG-Intron, Infergen, Alferon and IFN-omega (with or without ribavirin) and other drugs in development for the treatment of HCV (e.g. polymerase inhibitors) and therefore has the potential to be included as part of many combination therapeutic approaches to improve efficacy in anti-HCV therapy.
A previously completed Phase II non-responder combination study reported April 11, 2007 showed:
- a 42% Early Virologic Response(x) (EVR) with PRC compared to a 10% EVR with PR ((x) EVR = 2 log(10) or greater HCV viral load reduction at 12 weeks).
- a mean HCV viral load reduction ("VLR") of 1.63 log(10) (PRC) compared to a 0.92 log(10) reduction (PR).
- 90% viral load reduction (1 log(10)) reduction, or greater, at 12 weeks in 66% (8/12) of PRC patients, compared to only 40% (4/10) in patients in the PR treatment arm.
- EVR in 57% of null responders (4/7) in the PRC therapy arm (null responders = patients who have not achieved greater than a 0.4 log(10) viral load reduction on prior treatment with optimized PR).
Celgosivir combination therapy was well tolerated and resulted in no significant adverse events. As expected from previous experience, the most frequent side effects related to celgosivir were gastrointestinal in nature and were generally mild. Other frequently observed side effects were fatigue and flu-like symptoms - which are side effects usually associated with PR treatment.
Source:
MIGENIX Inc. 