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Eiger HCV NS4B Inhibitor Exhibits Synergy with Experimental HCV Protease Inhibitors

SUMMARY: The investigational hepatitis C virus (HCV) NS4B inhibitor clemizole demonstrated synergistic antiviral activity with the HCV protease inhibitors telaprevir and boceprevir -- meaning the combined effect was greater than the added effects of the 2 drugs used separately -- without increased toxicity, according to a laboratory study published in the July 1, 2010 Journal of Infectious Diseases.


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.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


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