data suggest that cellular immunity may be a fundamental deficit in
hardest-to-treat IL28B T/T genotype patients and is corrected by GI-5005
Data to be presented at annual meeting of the American Association
for the Study of the Liver Diseases
Colo. -- October 30, 2010 -- GlobeImmune Inc. today announced additional
data from the GI-5005-02 Phase 2b study demonstrating that GI-5005,
the company's investigational Tarmogen product, improved sustained
virologic response (SVR) by 12% in patients with genotype 1 chronic
hepatitis C virus (HCV) infection who had failed prior treatment with
standard of care (SOC, pegylated-interferon
alpha 2a [Pegasys] plus ribavirin). This study suggests that GI-5005
may have the potential to be the first successful therapeutic vaccine
for patients chronically infected with HCV.
Paul J. Pockros, MD, of Scripps Clinic will deliver the oral presentation
of the results in a late-breaker session at 6 p.m. EDT Monday November
1, 2010 at the 61st Annual Meeting of the American Association for
the Study of the Liver Diseases (AASLD) in Boston.
On an intent-to-treat basis (subjects who received at least one dose
of combination therapy), prior non-responders receiving GI-5005 plus
SOC as a triple therapy had an SVR rate of 17%, compared to an SVR
rate of only 5% in patients receiving SOC alone. Prior non-responders
in this study were defined as patients who did not clear virus after
a minimum of 12 weeks of SOC, including null responders, poor responders,
and partial responders. Relapsers and on-treatment breakthroughs were
not enrolled in the study. The most common adverse events associated
with GI-5005 were injection site reactions that were generally mild
and transient in nature. Discontinuation rates due to adverse events
in the GI-5005 triple therapy arm were comparable to the discontinuation
rates in the SOC alone arm.
"Only 4-7% of patients with genotype 1 HCV who were null, poor
or partial responders to their first course of pegylated interferon-based
therapy would be expected to achieve a sustained virologic response
with a second course of treatment," said Dr. Pockros. "In
this study, GI-5005 conferred a three-fold improvement in SVR, an
important treatment effect in this challenging patient population."
Additional immunology data from the study will be presented in a poster
on Tuesday November 2, 2010 by John M. Vierling, MD, of Baylor College
of Medicine. These data show that GI-5005 improved HCV-specific T
cell responses 10-fold over SOC alone in patients with the IL28B T/T
genotype (~20% of chronically infected patients), the subgroup most
likely to fail treatment with SOC alone. Patients with the IL28B T/T
genotype receiving SOC alone had an HCV-specific cellular immune response
that was 17-fold lower than patients in the IL28B C/C or C/T subgroups.
The improved HCV-specific T cell immunity in IL28B T/T patients receiving
GI-5005 plus SOC correlates with previously reported data that demonstrated
GI-5005 increased SVR rates by 60 percent in interferon-naive T/T
patients compared to T/T patients receiving SOC alone.
"These data suggest that the fundamental deficit in patients
carrying the T allele of the IL28B gene is a deficit in adaptive cellular
immunity, the mechanism that GI-5005 was designed to address,"
said David Apelian, MD, PhD, Chief Medical Officer at GlobeImmune.
"We are confident that GI-5005 will become a cornerstone of HCV
therapy, particularly for difficult to treat populations, such as
IL28B T/T patients.""
A 40 patient expansion of this study in patients having the IL28B
T/T genotype was initiated last week to further explore the potential
treatment effect of GI-5005 in this patient population.
GI-5005 is a therapeutic vaccine candidate designed to generate HCV-specific
T-cell responses and improve virologic responses in patients with
chronic hepatitis C virus infection.
Inc. is a private company developing therapeutic vaccines called Tarmogens
for the treatment of cancer and infectious diseases. Tarmogens generate
activated killer T cells that are designed to locate and eliminate
virally-infected cells and/or cancer cells. The company's lead product
candidate, GI-5005, is a Tarmogen being developed for the treatment
of chronic hepatitis C virus (HCV) infection. GI-5005 is designed
to complement both the current standard of care and emerging novel
therapies for HCV. The company's lead oncology program, GI-4000, targets
cancers caused by mutated versions of the Ras oncoprotein. GI-4000
is being investigated in clinical trials for the treatment of pancreas
cancer as well as other cancers that contain mutated Ras, including
non-small cell lung cancer and colorectal cancer. In May 2009, the
company announced a global partnership with Celgene focused on the
discovery, development and commercialization of multiple product candidates
for the treatment of cancer.
For additional information, please visit the company's website at
study: Scripps Clinic, La Jolla, CA; Center for the Study of Hepatitis
C, Weill Cornell Medical College, New York, NY; Department of Medicine,
University of Arizona College of Medicine, Tucson, AZ; Center for
Liver Diseases, University of Miami School of Medicine, Miami, FL;
Department of Medicine, University of Colorado Denver, Aurora, CO;
Department of Internal Medicine, University of Texas Southwestern
Medical Center at Dallas, Dallas, TX; Department of Medicine and Surgery,
Baylor College of Medicine, Houston, TX; St. Luke's Episcopal Hospital,
Houston, TX; Alamo Medical Research, San Antonio, TX; South Denver
Gastroenterology, PC, Englewood, CO; Center for Disease of the Liver
and Pancreas, Swedish Medical Center, Englewood, CO; University of
Hawaii, Honolulu, HI; Liver Institute of Virginia, Bon Secours Health
System, Newport News, VA; Columbia University College of Physicians
& Surgeons, New York, NY; QST Consultations, Allendale, MI; GlobeImmune,
Vierling study 1973: Department of Medicine and Surgery, Baylor College
of Medicine, Houston, TX; St. Luke's Episcopal Hospital, Houston,
TX; Duke Clinical Research Institute, Duke University Medical Center,
Durham, NC; Center for the Study of Hepatitis C, Weill Cornell Medical
College, New York, NY; Department of Medicine, University of Arizona
College of Medicine, Tucson, AZ; Center for Liver Diseases, University
of Miami School of Medicine, Miami, FL; University of Texas Southwestern
Medical Center at Dallas, Dallas, TX; Liver Institute of Virginia,
Bon Secours Health System, Newport News, VA; University of Hawaii,
Honolulu, HI; Alamo Medical Research, San Antonio, TX; GlobeImmune,
Louisville, CO; University of Pennsylvania, Philadelphia, PA; QST
Consultations, Allendale, MI.
IM Jacobson, TD Boyer, and others. GI-5005 Therapeutic Vaccine Plus
Peg-IFN/Ribavirin Improves Sustained Virologic Response Versus Peg-IFN/Ribavirin
In Prior Non-Responders With Genotype 1 Chronic HCV Infection. 61st
Annual Meeting of the American Association for the Study of Liver Diseases
(AASLD 2010). Boston, October 29-November 2, 2010. Abstract LB-6.
JG McHutchison, IM Jacobson, and others. GI-5005 Therapeutic Vaccine
Improves Deficit In Cellular Immunity In IL28B Genotype T/T, Treatment-Naive
Patients With Chronic Hepatitis C Genotype 1 When Added To Standard
of Care (SOC) Peg-IFN-alfa-2A/Ribavirin. 61st Annual Meeting of the
American Association for the Study of Liver Diseases (AASLD 2010). Boston,
October 29-November 2, 2010. Abstract 1973.
GI-5005 HCV Therapeutic Vaccine Increases SVR Prior Treatment Failures.
Press release. October 30, 2010.
GlobeImmune Announces Expansion of GI-5005 Phase 2 Trial. Press release.
October 28, 2010.