GI-5005 -Therapeutic HCV Vaccine Has Benefit in Some Subgroups

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GI-5005 -Therapeutic HCV Vaccine Has Benefit in Some Subgroups

BOSTON – A therapeutic vaccine against the hepatitis C virus was associatedwith a significantly higher sustained virologic response rate when added tostandard-of-care treatment, and the findings justify further development of the vaccine, Dr. Pockros, AGAF, reported at the annual meeting of the American Association for the Study of Liver Diseases.In the proof-of-concept trial, 133 patients infected with hepatitis C virus(HCV) genotype 1 were randomized to either triple therapy comprising the experimental GI-5005 vaccine, which is designed to elicit a T-cell response specific to HCV, along with pegylated interferonalfa-2b plus ribavirin (P/R), or the standard P/R therapy alone.The primary outcome measure was sustained virologic response (SVR), definedas undetectable HCV RNA at 6 months after treatment, said Dr. Pockrosof the Scripps Clinic in La Jolla, Calif.The 68 patients in the experimental group

initially received monotherapy with the vaccine, consisting of five weekly injections followed by two monthly injections for a 12-week lead-in period,before progressing to the standard-of care P/R treatment and once-monthlyinjections. The 65 patients in the control group received standard-of-care P/R treatment alone. In both groups, treatment duration was 48 weeks for treatment-naive patients and 72 weeks for those who had a poor or partial response to prior P/R treatment.Among the study’s treatment-naive patients,58% of those who received the vaccine achieved SVR, compared with 48% of those who received P/R alone. Among the prior poor and partial responders, the respective SVR rates in the vaccine and control groups were 17% and 5%, Dr. Pockros reported. “There was a slight benefit in the treatment-naive and nonresponders, [but] this was numerical only and was not statistically significant,†he said. However, the overall benefit

in thevaccine group vs. control group was statistically significant, with respective SVR rates of 47% and 35%, he noted.The vaccine strategy appears to be safe. “The most common associated adverse events were mild, transient injection-site reactions,†said Dr. Pockros, and the discontinuation rates due to adverseevents were comparable (13%) in both groups.Of particular interest, Dr. Pockros noted,was the T-cell response in a subgroupof difficult-to-treat patients receiving the vaccine. Previous studies have suggested that patients carrying the T allele of the IL28 gene are at high risk of treatment failure with the standard interferon-based therapy.The T-cell response in vaccine-treated patients, as measured by interferon-gamma enzyme-linked ImmunoSpot assay, “mimicked what we saw with a virologic response,†he said. “Four of five T/T allele patients had a T-cell response – one did not actually get treated – but

none ofthe patients who received standard of care had a T-cell response.â€This finding is consistent with the hypothesis that the GI-5005 vaccine corrects a fundamental deficit in cellular immunity in IL28B T/T genotype patients, he said. Although the findings need to beconfirmed in studies with larger patient populations, the vaccine will likely be genotype specific, he noted.Because the immune response is similar to that observed in HCV-infected patients who are able to clear the virus without treatment, future studies will evaluate the efficacy of monotherapy with the vaccine in genotype-specific patients, Dr. Pockros said.The proof-of-concept study was funded by GlobeImmune, manufacturer ofthe vaccine. Dr. Pockros disclosed financial relationships with GlobeImmune, Genentech, Vertex, Merck, Gilead, Abbott,Pfizer, Phenomix, Tibotec, Pharmasset,3RT, Novartis, & , Achillon, Regulus, Debio,

Zymogenetics, and Human Genome Sciences.http://www.gastro.org/journals-publications/gi-hepatology-news/GI_-_Hepatology_News_-_July_2011.pdf

http://Hepatitis Cnewdrugs.blogspot.com/2011/07/gi-5005-therapeutic-hcv-vaccine-has.html