The
study also found that clemizole showed an additive, rather than
synergistic, effect when combined with interferon, ribavirin,
or the HCV polymerase inhibitors valopicitabine and HCV-796
(both discontinued).
The
study authors, led by Jeffrey Glenn from Stanford University,
founder of Eiger BioPharmaceuticals (the company developing
clemizole), concluded that "Inclusion of clemizole in future
anti-HCV cocktails can represent an attractive paradigm for
increasing current virologic response rates."
Below is the text of a press release from Eiger BioPharmaceuticals
providing more information about the study.
Eiger
BioPharmaceuticals Announces New HCV Synergy Data
Publication
describes high level of synergy of clemizole with protease inhibitor
class
Palo
Alto, Calif. -- July 1, 2010 -- Eiger BioPharmaceuticals, Inc.,
a biotechnology company developing antiviral therapies, announced
today the publication of research from the lab of Stanford scientist
and Eiger Founder, Dr. Jeffrey Glenn, MD, PhD and colleagues
entitled, "The Hepatitis C Virus (HCV) NS4B RNA Binding
Inhibitor Clemizole is Highly Synergistic with HCV Protease
Inhibitors."
"This work demonstrates that clemizole can yield high-level
synergy with the protease inhibitor class," said David
Cory, President and CEO of Eiger. "Inclusion of clemizole
in future anti-HCV cocktails represents an attractive paradigm
for increasing virologic response rates and may minimize unwanted
side effects and combat drug resistance to HCV protease inhibitors."
"Clemizole appears to be able to dramatically increase
the in vitro efficacy of other agents such as the NS3 protease
inhibitors in advanced clinical development," said Jeffrey
Glenn, M.D., Ph.D., Founder of Eiger. "The addition of
clemizole to regimens may allow protease inhibitors to be used
at lower doses, thereby maintaining the desired antiviral efficacy
while avoiding the toxicities associated with the protease inhibitors
such as severe rash and anemia. Clemizole has the potential
to be an ideal component of future anti-HCV cocktails."
About NS4B and Clemizole
Binding of the non-structural protein NS4B to the 3' terminus
of the HCV negative RNA strand is a recently identified target
for drug intervention. The requirement of this target for viral
replication has been genetically validated. The two component
nature of this target, involving interaction between NS4B and
HCV-RNA, creates mutational constraints that should decrease
resistance to pharmacologic inhibitors, compared to agents designed
against a single component target such as the NS3 protease.
Clemizole hydrochloride was identified as a specific inhibitor
of NS4B-RNA binding. The anti-HCV activity of clemizole is currently
being investigated across genotypes in multiple HCV clinical
proof of concept trials as a cocktail component with standard
of care medications.
About Eiger BioPharmaceuticals, Inc.
Eiger is focused on the discovery and development of new antiviral
agents against novel targets for the treatment of hepatitis
virus infections. Eiger's pipeline includes repurposed clinical
stage therapeutic agents as well as preclinical NCEs from discovery
that exhibit antiviral activity against Hepatitis C, Hepatitis
D, and other viruses. Eiger investors include InterWest Partners
(www.interwest.com) and Vivo Ventures (www.vivoventures.com).
For more information see www.eigerbio.com.
Investigator affiliations: Divisions of Infectious Diseases
& Geographic Medicine and Gastroenterology and Hepatology,
Stanford University School of Medicine, Stanford, CA; Veterans
Administration Medical Center, Palo Alto, CA.
7/9/10
Reference
S
Einav, HD Sobol, E Gehrig, and JS Glenn. The hepatitis C virus
(HCV) NS4B RNA binding inhibitor clemizole is highly synergistic
with HCV protease inhibitors. Journal of Infectious Diseases
202(1): 65-74 (Abstract).
July 1, 2010.
Other source
Eiger BioPharmaceuticals. Eiger BioPharmaceuticals Announces
New HCV Synergy Data. Press release. July 1, 2010.
