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GS-4774
Has anyone heard anything about Gilead GS-4774? This is a Tarmogen T cell immunity stimulator.
Nevertheless gene therapy is the way to go. Lets hope we all live to see a cure for the curse we have to live with.
Well 7m is a nice figure. But if you compare to what research costs today. This is is very small number. Compare it to what DARPA gets funding wise developing mind blowing technologies and goodies for the military. And that 7million is a tear drop.
There are 360 million of us sick with Hbv. And funding for a cure is just not there.
And you have to feel for these small companies too that try to do good getting some funding.for their projects. but most often or not even if they happen to come across something like Replicor did - they wont have the funds to take the product to market. And this is where big pharma comes in. That may buy the project. Or buy it and think about what to do with it in the future.
There are 360 million of us sick with Hbv. And funding for a cure is just not there.
And you have to feel for these small companies too that try to do good getting some funding.for their projects. but most often or not even if they happen to come across something like Replicor did - they wont have the funds to take the product to market. And this is where big pharma comes in. That may buy the project. Or buy it and think about what to do with it in the future.
it is good thing that more and more companies coming to fight against HBV
Tuesday, October 8, 2013
ISIS/GSK and Tekmira Come Out with HBV Knockdown Plans
If you did not appreciate the value the pharmaceutical industry has come to place on the HBsAg knockdown concept for achieving a functional cure for chronic Hepatitis B (HBV) infection, the last two days will have woken you up.
Yesterday, ISIS Pharmaceuticals reported that it had received a $7M milestone payment related to the development of an antiviral RNaseH development candidate (ISIS-GSK3Rx, aka ISIS-HBVRx) which, although undisclosed for competitive reasons, has got to be for HBV. And today, Tekmira publicly announced that they will file an IND for an HBV-RNAi candidate in 2014 while hinting at the partnering potential of such a treatment candidate.
Arrowhead Research is thus not alone in their efforts any more. Coincidentally, Arrowhead reported today the completion of their enrollment of the phase I single-dose, healthy volunteer study with ARC520, their DPC-delivered candidate for chronic HBV. Accordingly, the dose escalation was able to run through all the pre-planned 6 dose cohorts up to the top dose of 2.0mg/kg.
Apparently, there were no signs of significant dose-related toxicities. The only finding of concern among the 36 volunteers, 24 of which received drug, was 2 cases of lightheadedness of uncertain clinical relevance. As these occurred at the highest dose, it seems that the company suspects that it could have been drug-related although the study remains blinded for follow-up.
A dose of 2mg/kg without any serious adverse events or dose-limiting toxicities is a great start for DPC delivery technology. This is especially the case when one considers that the single-molecule subQ version of DPC that I hope will form the basis for the upcoming pipeline candidates, except for the next one perhaps, will be much more potent than the two-molecule version of intravenously delivered ARC520 based on the non-human primate data presented at last year's OTS meeting.
With 2mg/kg of ARC520, I further believe that HBsAg knockdowns of over 90% are likely. The biggest challenge going forward with this program will be setting a knockdown goal and getting the dose and dose frequency right.
This should work great with zadaxin. And high doses of vitamin d and c. That would be an intersting study
TITLE: Safety, Tolerability and Immunogenicity of GS-4774, an HBV-specific Therapeutic Vaccine, in Healthy Volunteers
AUTHORS (FIRST NAME, LAST NAME): Anuj Gaggar1, Claire Coeshott2, Mani Subramanian1, John G. McHutchison1, David Apelian2
Institutional Author(s):
INSTITUTIONS (ALL): 1. Gilead Sciences, Foster City CA, CA, United States.
2. Globeimmune, Louisville, CO, United States.
ABSTRACT BODY: Background: Chronic HBV (CHB) infection is in part characterized by diminished T cell responses to viral antigens. A therapeutic vaccine enhancing the adaptive immune response to HBV may provide a strategy to improve the rate of HBsAg loss and seroconversion in CHB patients compared to nucleos(t)ide HBV polymerase inhibitors alone. GS-4774 is a yeast-based vaccine (Tarmogen) expressing a chimeric protein comprising of 60 amino acids of HBV X protein, the full 399 amino acids of HBV surface protein, and 182 amino acids of the HBV core protein.. The aim of this study was to evaluate the safety and immunogenicity of GS-4774 in healthy volunteers.
Methods: A Phase 1 study was conducted in healthy volunteers (n=60) to determine the safety and immunogenicity of GS-4774 using different doses and schedules. Doses of 10 yeast units (YU), 40 YU or 80 YU/dose were evaluated as either a) weekly dosing for 5 doses then a single monthly dose, or b) monthly doses for 3 consecutive months. The immune response to GS-4774 was assessed on Days 15, 29, 36, 57 and 85 by lymphocyte proliferation assays (LPA), IFN-γ ELISpot assays, and antibody response to specific HBV antigens.
Results: GS-4774 was well tolerated with no serious adverse events, no grade 3 or 4 adverse events, and no laboratory abnormalities observed in the study. Adverse events were more frequent with weekly dosing compared with monthly dosing and at the 80YU dose compared to the 10YU and 40YU group. There was one treatment discontinuation due to adverse event (skin reaction) in the 80 YU cohort. Available immunogenicity data until day 36 are summarized in the table. The majority of subjects demonstrated evidence of an HBV-specific immune response as assessed by LPA. No dose response in HBV-specific immunogenicity of GS-4774 was observed by LPA, and monthly dosing was similar to weekly dosing. An early HBV-specific T-cell response by IFN-γ ELISpot was observed in a greater number of subjects receiving the 10YU dose. As expected given the cellular immune targeting characteristics of the platform, no antibody response to core and surface antigens was observed at the early time points. Complete immunological and safety results of the study will be presented.
Conclusions: GS-4774 was well tolerated, and elicits HBV specific immune activation at the lowest monthly dose of 10 YU. Further evaluation of GS-4774 in patients with chronic hepatitis B is warranted.
10 YU 40 YU
Weekly Monthly Weekly Monthly
LPA Response, n/N (%) 5/7 (71) 3/4 (75) 7/9 (78) 9/9 (100)
ELISpot Response, n/N (%) 5/10 (50) 8/10 (80) 3/10 (30) 1/10 (10)
AUTHORS (FIRST NAME, LAST NAME): Anuj Gaggar1, Claire Coeshott2, Mani Subramanian1, John G. McHutchison1, David Apelian2
Institutional Author(s):
INSTITUTIONS (ALL): 1. Gilead Sciences, Foster City CA, CA, United States.
2. Globeimmune, Louisville, CO, United States.
ABSTRACT BODY: Background: Chronic HBV (CHB) infection is in part characterized by diminished T cell responses to viral antigens. A therapeutic vaccine enhancing the adaptive immune response to HBV may provide a strategy to improve the rate of HBsAg loss and seroconversion in CHB patients compared to nucleos(t)ide HBV polymerase inhibitors alone. GS-4774 is a yeast-based vaccine (Tarmogen) expressing a chimeric protein comprising of 60 amino acids of HBV X protein, the full 399 amino acids of HBV surface protein, and 182 amino acids of the HBV core protein.. The aim of this study was to evaluate the safety and immunogenicity of GS-4774 in healthy volunteers.
Methods: A Phase 1 study was conducted in healthy volunteers (n=60) to determine the safety and immunogenicity of GS-4774 using different doses and schedules. Doses of 10 yeast units (YU), 40 YU or 80 YU/dose were evaluated as either a) weekly dosing for 5 doses then a single monthly dose, or b) monthly doses for 3 consecutive months. The immune response to GS-4774 was assessed on Days 15, 29, 36, 57 and 85 by lymphocyte proliferation assays (LPA), IFN-γ ELISpot assays, and antibody response to specific HBV antigens.
Results: GS-4774 was well tolerated with no serious adverse events, no grade 3 or 4 adverse events, and no laboratory abnormalities observed in the study. Adverse events were more frequent with weekly dosing compared with monthly dosing and at the 80YU dose compared to the 10YU and 40YU group. There was one treatment discontinuation due to adverse event (skin reaction) in the 80 YU cohort. Available immunogenicity data until day 36 are summarized in the table. The majority of subjects demonstrated evidence of an HBV-specific immune response as assessed by LPA. No dose response in HBV-specific immunogenicity of GS-4774 was observed by LPA, and monthly dosing was similar to weekly dosing. An early HBV-specific T-cell response by IFN-γ ELISpot was observed in a greater number of subjects receiving the 10YU dose. As expected given the cellular immune targeting characteristics of the platform, no antibody response to core and surface antigens was observed at the early time points. Complete immunological and safety results of the study will be presented.
Conclusions: GS-4774 was well tolerated, and elicits HBV specific immune activation at the lowest monthly dose of 10 YU. Further evaluation of GS-4774 in patients with chronic hepatitis B is warranted.
10 YU 40 YU
Weekly Monthly Weekly Monthly
LPA Response, n/N (%) 5/7 (71) 3/4 (75) 7/9 (78) 9/9 (100)
ELISpot Response, n/N (%) 5/10 (50) 8/10 (80) 3/10 (30) 1/10 (10)
http://clinicaltrials.gov/ct2/show/NCT01943799?term=HBV++California&rank=21
Looks like in UCLA they are going with it. And Kaiser over by you is doing testing.
Looks like in UCLA they are going with it. And Kaiser over by you is doing testing.
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