By Michael Smith , North American Correspondent, MedPage Today
Published: November 02, 2010
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
BOSTON -- An experimental therapeutic vaccine against hepatitis C improved response rates by 12% compared with standard care in a small clinical trial, a researcher reported here.
The phase II trial included both treatment-naive patients and those who had not responded to previous care with the standard combination of ribavirin and pegylated interferon, according to Paul Pockros, MD, of the Scripps Clinic in La Jolla, Calif.
Results in both subgroups were similar to the overall outcome but did not reach statistical significance compared with standard care, Pockros told a late-breaker session at the annual meeting of the American Association for the Study of Liver Diseases.
But the findings, based on just 133 patients, are enough to justify continued development of the vaccine, Pockros said, including tests to see if it can be effective without the standard hepatitis C treatment regimen, which has difficult side effects.
The vaccine -- dubbed GI-5005 -- is a recombinant, inactivated yeast that expresses hepatitis antigens, Pockros said.
The immune response generated by the vaccine is similar to that seen among patients who are able to clear the virus without medication -- a modest response to the viral envelope proteins and a robust response to the nonstructural proteins NS3 and NS5.
Patients in the study were randomly assigned to get the vaccine or not. Those getting vaccine first had a 12-week run-in, during which they got five weekly doses of GI-5005, delivered subcutaneously then followed by two monthly doses.
They then got the vaccine on a monthly basis, along with the two standard hepatitis C drugs, ribavirin, and pegylated interferon.
The comparison group, including 65 of the 133 participants, got standard care only.
In both groups, treatment-naive patients were treated for 48 weeks, while previous nonresponders got 72 weeks of treatment. The primary endpoint was sustained virologic response, defined as undetectable virus six months after the end of treatment.
The researchers found:
• 58% of treatment-naive patients who got the vaccine had a sustained virologic response, compared with 48% of those getting standard treatment.
• 17% of previous nonresponders had a sustained virologic response if they got the vaccine compared with 5% of those on standard care.
• And overall, the vaccine yielded a 47% response rate, compared with 35% for standard care.
• The first two results did not reach statistical significance, but the last was significant at P=0.037.
Pockros said that no unexpected adverse effects surfaced during the trial; there was a 13% rate of discontinuation in each study arm due to side effects.
The GI-5005 vaccine, he said, is a "novel approach to hepatitis C" that appears to be safe but needs more study.
A "benign" therapeutic vaccine might be advantageous, according to Douglas LaBrecque, MD, of the University of Iowa in Iowa City, Iowa, who was not part of the study but who moderated the session at which the data was presented.
That would be especially true, he told MedPage Today "if you could eliminate some of the other medications, either interferon or the small molecules, which have their own side effects."
But this study was so preliminary and had such small numbers, LaBrecque stressed, that "all you can say is that it wasn't a total failure."
The study was supported by GlobeImmune, of Louisville, Colo. Pockros reported financial links with Genentech, Vertex, Merck, Gilead, Abbott, Pfizer, Phenomix, Tibotec, Pharmasset, 3RT, Novartis, J&J, Achillon, Regulus, GlobeImmune, Debio, Zymogenetics, and Human Genome Sciences.
LaBrecque had no disclosures.
Primary source: American Association for the Study of Liver Diseases
Source reference:
Pockros P, et al "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" AASLD 2010; Abstract LB-6.
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