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Hep C vaccine shows promise
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By Kirsty Barnes
http://www.biopharma-reporter.com
21/08/2007 - An experimental peptide-based hepatitis C vaccine has shown promise in interim Phase II trial data, according to its developer Intercell.
The hepatitis C virus (HCV) is a major cause of chronic liver disease and 170m people worldwide carry the disease, however, currently there is no available vaccine.
Intercell's vaccine (IC41) comprises of eight T-cell antigens, combined with its first-generation poly-arginine adjuvant (IC30). It is designed to stimulate T-cell responses against HCV protein structures and reduce viral load.
Intercell said that the first data to be analysed from half of the 50 treatment-naive study participants showed that its vaccine met the primary endpoint of achieving a statistically significant viral load (HCV-RNA) reduction.
During the study, patients received eight injections of IC41, bi-weekly for 14 weeks. In addition to meeting the primary endpoint, a "very good safety profile" was achieved, the Austrian drug development firm said.
Intercell added that the trial subjects were chronically infected with HCV Genotype 1, which is notoriously difficult to treat with the current gold standard, interferon/ribavirin.
However, the firm said that the data still has to be interpreted with caution given the small sample size. The full study data is expected at the beginning of 2008. An extended analysis of how the therapeutic effect relates to the induction of T-cell responses is also expected at this point.
"The data opens the door for therapeutic vaccination in the arena of existing and future treatment options - but [is] not yet a breakthrough for vaccination as monotherapy."
"The new data obtained encourages us very much to further strengthen our HCV franchise and to accelerate our efforts towards obtaining an HCV therapeutic vaccine", added Gerd Zettlmeissl, CEO of Intercell.
As part of this, Intercell said that in conjunction with its HCV vaccine co-development partner, Novartis, it will define a further development strategy that might also take advantage of an enlarged antigen portfolio and of IC31, its second-generation adjuvant that has "recently demonstrated the generation of T-cell responses, in human vaccine trials, to a level not yet seen for other known adjuvants".
In 2006 worldwide sales of HCV drugs totalled 3.5bn.
Intercell's therapeutic Hepatitis C vaccine meets primary endpoints in Phase II interim analysis
Intercell news release
* First data from 25 patients reveals statistically significant viral load reduction and very good safety profile
* Data opens door for therapeutic vaccination in the arena of existing and future treatment options - but not yet a breakthrough for vaccination as monotherapy
* Data still has to be interpreted with caution given the small sample size - full study data expected for Q1 2008
Vienna, Austria, 20 August 2007. Today, Intercell AG (ICLL) announced the analysis of Phase II interim data for its peptide-based therapeutic Hepatitis C vaccine (IC41) in an exploratory clinical study targeting treatment-naive Hepatitis C patients. The vaccine comprises eight T-cell antigens and Intercell's first-generation poly-arginine adjuvant (IC30). It is designed to stimulate T-cell responses against viral protein structures conserved throughout the major HCV genotypes, in order to reduce viral load in the blood of chronically infected patients.
The current study comprises 50 patients chronically infected with Genotype 1 of the Hepatitis C virus, which is known to be very difficult to treat with Interferon/Ribavirin standard therapy. The patients enrolled in the study have not received any other therapy and were given 8 intradermal injections of the IC41 vaccine in bi-weekly intervals for 14 weeks. This intensified vaccination schedule was derived from a recent optimization study aimed at improving the vaccine's T-cell immune response. The desired outcome of the ongoing study is the demonstration of a constant and sustained decline in HCV viral load that is increased by reiterative vaccinations during the treatment period.
In the current interim analysis, 25 patients have been evaluated in the "per protocol" population. The data obtained shows that the primary endpoint set for this study, namely a statistically significant sustained HCV- RNA decline, has been met. In the second week after the final vaccination, a 40 % reduction of viral load (0.2 log) was observed in comparison to the baseline prior to vaccination. The therapeutic effect of the vaccine on the viral load is small, but found to be significant when data was submitted for rigorous statistical analysis (p=0.0178).
The results are especially significant in the light of the observation that viral load reduction is increasing with the number of vaccinations and is most pronounced two weeks after the vaccination schedule has been concluded. The study included patients with various levels of viral loads. In the subset of patients (N=12) with high viral load (> 2 million copies/ml) before treatment, a statistically significant (p=0.0168) average decline of 60 % (0.4 log) was achieved. Thus, it seems that the therapeutic effect is more pronounced when the patients' immune system is unable to keep the viral load in check.
Final results of the study with the full set of patients and an analysis of HCV-RNA and T-cell responses until 24 weeks after the last vaccination are expected in early 2008. Furthermore, an extended analysis of how the therapeutic effect relates to the induction of T-cell responses has to be awaited until the final outcome of the trial.
Although the interim analysis is restricted by the limited number of subjects evaluated at this stage, the present findings - if confirmed by the final data - would indicate for the first time that a therapeutic vaccination schedule is able to reduce HCV viral load and has thereby potentially opened a new door for HCV treatment.
Although options for the treatment of chronic Hepatitis C with Interferon/Ribavirin have improved, treatment will remain very difficult and a significant unmet medical need, especially in the case of Genotype 1. Immunotherapies, and possibly therapeutic vaccines, might become an option in the arena of existing and future HCV combination treatments. Thus, Intercell and its co-development partner for therapeutic Hepatitis C vaccines, Novartis, will define a further development strategy that might also take advantage of an enlarged antigen portfolio and of IC31, Intercell's second-generation adjuvant that has recently demonstrated the generation of T-cell responses, in human vaccine trials, to a level not yet seen for other known adjuvants.
"The new data obtained encourages us very much to further strengthen our HCV franchise and to accelerate our efforts towards obtaining an HCV therapeutic vaccine", states Gerd Zettlmeissl, CEO of Intercell.
The company noted that it hopes the study would show that the reiterative vaccinations in the treatment period would lead to an increased constant and sustained decline in viral load. "The present findings, if confirmed by the final data, would indicate for the first time that a therapeutic vaccination schedule is able to reduce Hepatitis C virus viral load and has thereby potentially opened a new door for treatment," Intercell added. Full study data is expected to be available in the first quarter of 2008.
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