Adding
Celgosivir to Standard Hepatitis C Therapy Increases the Likelihood of Early Response
Rate in Prior Non-responders Several
targeted antiviral agents are under study for the treatment of chronic hepatitis
C, especially in “hard to treat” patients such as those with HCV genotype 1 and
non-responders to prior therapy.  Celgosivir
(MX-3253) is a member of a new class of antiviral drugs. Its active metabolite,
castanospermine, is a potent inhibitor of a-glucosidase I, a host enzyme required
for viral assembly and release
Canadian researchers conducted a Phase II, multicenter, double-blind study of
celgosivir in 57 patients with chronic genotype 1 HCV infection stratified by
prior treatment status as non-responders (n = 36) or partial responders (n = 21).
Subjects were randomly assigned to 3 treatment groups:
- celgosivir
400 mg once daily in combination with pegylated interferon and ribavirin: 15 non-responders,
3 partial responders;
- celgosivir
400 mg once daily in combination with pegylated interferon alone: 11 non-responders,
9 partial responders;
- placebo
plus pegylated interferon and ribavirin (PR): 10 non-responders, 9 partial responders.
Pegylated
interferon and ribavirin were administered using standard weight-based dosing.
The total treatment duration was 12 weeks. Data
were analyzed twice, since half the viral load samples required re-testing after
the initial analysis. Results from both analyses were presented at the 42nd Annual
Meeting of the European Association for the Study of the Liver this month
in Barcelona, Spain. Below
is an excerpt from a press release from Migenix -- the developer of celgosivir
-- announcing the recent study results: New
Clinical Study Results Indicate Higher Early Virologic Response with Celgosivir
Combination Therapy in HCV Non-Responders Data
to be Presented April 15th at EASL Conference in Barcelona, Spain VANCOUVER
and SAN DIEGO, CA, April 11 -- PRNewswire-FirstCall -- MIGENIX Inc. (TSX: MGI,
OTC: MGIFF), a clinical-stage developer of drugs for infectious diseases, has
received new top-line results confirming the previously announced clinical results
(November 6, 2006) indicating evidence of clinical benefit, safety, and tolerability
in a Phase II study using the oral alpha-glucosidase inhibitor, celgosivir (MX-3253),
in combination with pegylated interferon and ribavirin. In
addition to confirming the overall conclusions of the original study analysis,
retesting resulted in a larger percentage of patients achieving an Early Virologic
Response ("EVR") rate with celgosivir plus peginterferon alfa-2b and
ribavirin (the "triple combination") as compared to treatment with peginterferon
alfa-2b and ribavirin alone (the "control treatment") in patients with
chronic hepatitis C virus genotype 1 infections who were characterized as non-responders
to prior therapy with optimized pegylated interferon plus ribavirin, achieving:
- 42%
(5/12) EVR with the celgosivir triple combination arm compared to 10% (1/10) EVR
in the control treatment arm. This compares with 33% (4/12) EVR (triple combination)
vs 10% (1/10) (control treatment) in the original study results. EVR = 2 log10
or greater HCV viral load reduction at 12 weeks.
- 1.63
log10 (triple combination) mean HCV viral load reduction ("VLR")
compared to a 0.92 log10 VLR (control treatment). This compares with
a 1.2 log10 VLR (triple combination) vs a 0.4 log10 VLR
(control treatment) in the original study results.
- A
more rapid onset of treatment effect as measured by VLR within the first 2 weeks
of therapy in the triple combination as compared to the control treatment.
These
new top-line results complete the retesting announced February 6, 2007 as a result
of Schering-Plough Corporation ("Schering") having informed Migenix
that approximately 50% of the original viral load samples from the study, which
Schering tested under a Material Transfer and License Option Agreement between
the companies, required retesting.
AnnKatrin
Petersen, MD, Vice President, Clinical Development of Migenix stated, "The
increase in EVR to 42% after retesting (33% previously) for the celgosivir triple
combination group in these very difficult to treat patients, along with the clear
evidence of rapid reduction in viral load give us increased confidence in the
potential of celgosivir to contribute in the treatment of HCV patients."
Jim DeMesa, MD, President and CEO of Migenix added, "This
confirmation of our previously announced results allows us to now focus on providing
a data package to Schering-Plough over the next few weeks for their limited period
of exclusive review under our License Option Agreement. The better EVR results
seen upon retesting, especially in these very difficult-to-treat non-responder
patients, reinforces our optimism in celgosivir's potential to improve treatment
outcomes for these HCV patients with few therapeutic options."
Additional Information
About the Clinical Study
The
Phase II non-responder combination study was designed to determine, over 12 weeks
of treatment, the efficacy, safety, and tolerability of celgosivir in combination
with peginterferon alfa-2b, with or without ribavirin, in HCV-positive (genotype
1) patients who were non-responders or partial responders to prior therapy with
optimized pegylated interferon and ribavirin.
A total of 57 patients were enrolled into this Phase II study (36 were non-responders
and 21 were partial responders). Patients were randomized into three treatment
arms: (i) celgosivir (400 mg once daily) plus peginterferon alfa-2b plus ribavirin
("triple combination"); (ii) celgosivir (400 mg once daily) plus peginterferon
alfa-2b ("double combination"); and (iii) celgosivir placebo plus peginterferon
alfa-2b plus ribavirin ("control treatment"). Of the 36 non-responders,
30 patients completed the 12-weeks of treatment: 12 in the triple combination
arm, 8 in the double combination arm, and 10 in the control treatment arm. Beyond
the triple combination and control treatment results reported above the following
results were also consistent with the originally reported results: (a) the double
combination did not show a meaningful difference in mean viral load reduction
and EVR when compared to the control treatment in non-responder patients; and
(b) in the partial responder patient population, there were insufficient patients
(n=3) in the triple combination arm for any conclusions to be drawn and the double
combination showed less effect than the control treatment.
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 pegylated interferon and ribavirin. Only
7 of the 57 patients entering the study dropped out prior to week 12. 04/20/07 Sources K
Kaita, E Yoshida, D Kunimoto, and others. Ph II proof of concept study of celgosivir
in combination with peginterferon alfa-2b and ribavirin in chronic hepatitis C
genotype 1 non-responder patients. 42nd Annual Meeting of the European Association
for the Study of the Liver. April
11 - 15, 2007, Barcelona,
Spain. Migenix.
New Clinical Study Results Indicate Higher Early Virologic Response with Celgosivir
Combination Therapy in HCV Non-Responders. Press release. April 11, 2007.
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