Aa
ARC-520 P2 is starting...
http://www.clinicaltrials.gov/ct2/show?term=arc-520&rank=2
Eligibility
Ages Eligible for Study: 18 Years to 65 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Key Inclusion Criteria:
Have a diagnosis of HBeAg negative, immune active, chronic HBV infection and all of the following:
History of being HBsAg positive at 2 time points > 6 months apart
HBsAg titer > 1,000 IU/mL determined at screening
HBeAg negative at screening
HBV DNA 6 months of continuous, 0.5 mg/day oral entecavir, and a willingness to continue taking entecavir throughout the study.
Key Exclusion Criteria:
Female patients that have a positive pregnancy test or are lactating.
Acute signs of hepatitis/other infection (eg, moderate fever, jaundice, nausea, vomiting, and abdominal pain) evident within 4 weeks of screening and/or at the screening examination.
Hepatic transaminases (ALT or AST) > 100 IU/mL at screening.
Patients with antiviral therapy other than entecavir within 3 months of screening or prior treatment with interferon or a toll receptor agonist in the last 5 years.
Use within the last 6 months or an anticipated requirement for anticoagulants, corticosteroids, immunomodulators, or immunosuppressants.
Has any history of autoimmune disease especially autoimmune hepatitis.
Has human immunodeficiency virus (HIV) infection, as shown by the presence of anti-HIV antibody (sero-positive).
Is sero-positive for HCV, and/or a history of delta virus hepatitis.
Has a history of allergy to bee venom or history of hypersensitivity reaction requiring an emergency visit to a physician or hospital and/or requirement for treatment with steroids and/or epinephrine.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT02065336
Eligibility
Ages Eligible for Study: 18 Years to 65 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Key Inclusion Criteria:
Have a diagnosis of HBeAg negative, immune active, chronic HBV infection and all of the following:
History of being HBsAg positive at 2 time points > 6 months apart
HBsAg titer > 1,000 IU/mL determined at screening
HBeAg negative at screening
HBV DNA 6 months of continuous, 0.5 mg/day oral entecavir, and a willingness to continue taking entecavir throughout the study.
Key Exclusion Criteria:
Female patients that have a positive pregnancy test or are lactating.
Acute signs of hepatitis/other infection (eg, moderate fever, jaundice, nausea, vomiting, and abdominal pain) evident within 4 weeks of screening and/or at the screening examination.
Hepatic transaminases (ALT or AST) > 100 IU/mL at screening.
Patients with antiviral therapy other than entecavir within 3 months of screening or prior treatment with interferon or a toll receptor agonist in the last 5 years.
Use within the last 6 months or an anticipated requirement for anticoagulants, corticosteroids, immunomodulators, or immunosuppressants.
Has any history of autoimmune disease especially autoimmune hepatitis.
Has human immunodeficiency virus (HIV) infection, as shown by the presence of anti-HIV antibody (sero-positive).
Is sero-positive for HCV, and/or a history of delta virus hepatitis.
Has a history of allergy to bee venom or history of hypersensitivity reaction requiring an emergency visit to a physician or hospital and/or requirement for treatment with steroids and/or epinephrine.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT02065336
Dose of ARC520 HBV Drug Candidate to be Increased to 3mg/kg
Today, Arrowhead Research reported preliminary phase IIa safety and efficacy results of ARC520 in patients infected with HBV. The goal of this study is to determine the level of viral knockdown, especially HBsAg, following a single dose of ARC520.
Efficacy in-line with animal studies
The results for the 1mg/kg and 2mg/kg cohorts indicate that knockdowns are in-line with what has been seen with 2 molecule DPC-enabled RNAi in non-human primates, including the HBV-infected chimpanzee. The company could not be more specific about numbers since it is still a blinded study and the knockdown curves apparently haven’t stabilized yet after 8 weeks in the 2mg/kg cohort suggesting remarkably prolonged pharmacology.
In the chimp study, HBV load in serum was reduced by 1log at 2mg/kg, but determination of the HBsAg knockdown following a single administration was complicated by the fact that Arrowhead gave a second dose of ARC520 of 3mg/kg before the HBsAg knockdown at 2mg/kg had leveled off. With 2 doses of 2mg/kg and 3mg/kg 2 weeks spaced apart, the final knockdown was ~80%. This level of knockdown was likely an underestimate of the true efficacy of ARC520 since one of the two siRNAs was a mismatch and the chimp had very high viremia to start with. For the non-human primate study with ARC-AAT, Arrowhead’s new development candidate for alpha-1 antitrypsin, the knockdown with a single dose of 1.5mg/kg was ~75%.
Taken together, I expect that the knockdown at 2mg/kg to be somewhere around 70-75%.
Arrowhead extending to higher doses
While this level of knockdown in such a short period of time, would be superior to anything before in the HBV space, for comfort and competitive reasons, it is not all that exciting. What is more exciting is that Arrowhead is doing what I’ve always saidthey should be doing, namely testing higher doses than 2mg/kg.
This is because for 2-molecule DPC-RNAi, it is the amount of the endosomolytic peptide that is rate-limiting for knockdown efficacy. As shown in animal model after animal model (e.g. Wooddell et al. 2013), the efficacy achieved with 2mg/kg was well below maximal knockdown efficacy. However, when slightly extending the dose to 3mg/kg or 4mg/kg, the depth of knockdown increases tremendously.
In the case of ARC-AAT for example, a 75% knockdown at 1.5mg/kg became a knockdown of 90% at 3mg/kg, which was the same knockdown as with 6mg/kg indicating that a plateau had been reached. In the case of HBV, the plateau, based on 6mg/kg endosomolytic peptide was a virtual elimination of HBsAg in the serum.
Despite the various genes and doses, the picture is that the dose-response becomes very steep soon after 2mg/kg. Whether it is 3mg/kg or 4mg/kg is another question. Arrowhead is currently gearing up for these doses following phase I extension studies in healthy volunteers,
The most important news today therefore is that 3mg/kg in healthy volunteers was as well tolerated as 1mg/kg and 2mg/kg before (4mg/kg in the works). Indeed, it was even better tolerated since the skin reactions disappeared with the transient use of an oral anti-histamine.
Results from the 3mg/kg cohort in this dose-finding study should be presented at or around AASLD in November. Stay tuned.
Link : http://rnaitherapeutics.blogspot.com/2014/08/dose-of-arc520-hbv-drug-candidate-to-be.html
Today, Arrowhead Research reported preliminary phase IIa safety and efficacy results of ARC520 in patients infected with HBV. The goal of this study is to determine the level of viral knockdown, especially HBsAg, following a single dose of ARC520.
Efficacy in-line with animal studies
The results for the 1mg/kg and 2mg/kg cohorts indicate that knockdowns are in-line with what has been seen with 2 molecule DPC-enabled RNAi in non-human primates, including the HBV-infected chimpanzee. The company could not be more specific about numbers since it is still a blinded study and the knockdown curves apparently haven’t stabilized yet after 8 weeks in the 2mg/kg cohort suggesting remarkably prolonged pharmacology.
In the chimp study, HBV load in serum was reduced by 1log at 2mg/kg, but determination of the HBsAg knockdown following a single administration was complicated by the fact that Arrowhead gave a second dose of ARC520 of 3mg/kg before the HBsAg knockdown at 2mg/kg had leveled off. With 2 doses of 2mg/kg and 3mg/kg 2 weeks spaced apart, the final knockdown was ~80%. This level of knockdown was likely an underestimate of the true efficacy of ARC520 since one of the two siRNAs was a mismatch and the chimp had very high viremia to start with. For the non-human primate study with ARC-AAT, Arrowhead’s new development candidate for alpha-1 antitrypsin, the knockdown with a single dose of 1.5mg/kg was ~75%.
Taken together, I expect that the knockdown at 2mg/kg to be somewhere around 70-75%.
Arrowhead extending to higher doses
While this level of knockdown in such a short period of time, would be superior to anything before in the HBV space, for comfort and competitive reasons, it is not all that exciting. What is more exciting is that Arrowhead is doing what I’ve always saidthey should be doing, namely testing higher doses than 2mg/kg.
This is because for 2-molecule DPC-RNAi, it is the amount of the endosomolytic peptide that is rate-limiting for knockdown efficacy. As shown in animal model after animal model (e.g. Wooddell et al. 2013), the efficacy achieved with 2mg/kg was well below maximal knockdown efficacy. However, when slightly extending the dose to 3mg/kg or 4mg/kg, the depth of knockdown increases tremendously.
In the case of ARC-AAT for example, a 75% knockdown at 1.5mg/kg became a knockdown of 90% at 3mg/kg, which was the same knockdown as with 6mg/kg indicating that a plateau had been reached. In the case of HBV, the plateau, based on 6mg/kg endosomolytic peptide was a virtual elimination of HBsAg in the serum.
Despite the various genes and doses, the picture is that the dose-response becomes very steep soon after 2mg/kg. Whether it is 3mg/kg or 4mg/kg is another question. Arrowhead is currently gearing up for these doses following phase I extension studies in healthy volunteers,
The most important news today therefore is that 3mg/kg in healthy volunteers was as well tolerated as 1mg/kg and 2mg/kg before (4mg/kg in the works). Indeed, it was even better tolerated since the skin reactions disappeared with the transient use of an oral anti-histamine.
Results from the 3mg/kg cohort in this dose-finding study should be presented at or around AASLD in November. Stay tuned.
Link : http://rnaitherapeutics.blogspot.com/2014/08/dose-of-arc520-hbv-drug-candidate-to-be.html
Enrollment of P2a clinical trial had been done as I know, if you really wanna be a volunteer, take care of P2b at 2014Q4, of course depending on P2a result.
Hi FlyingHippo,
I am Ravi 33 years old, chronic Hep B (e-antigen negative) positive for last 5 years,
Could you please let me know that can i be a voluntary for yours trails in Arrowhead RNAi (ARC-520) treatment?
I saw many online Presentation about Arrowhead RNAi (ARC-520) it is really very grate news and this treatment looking promising also.
Please let me know whom need contact and how to approach to be voluntary for this treatment.
I am Ravi 33 years old, chronic Hep B (e-antigen negative) positive for last 5 years,
Could you please let me know that can i be a voluntary for yours trails in Arrowhead RNAi (ARC-520) treatment?
I saw many online Presentation about Arrowhead RNAi (ARC-520) it is really very grate news and this treatment looking promising also.
Please let me know whom need contact and how to approach to be voluntary for this treatment.
Hi, i have been reading some posts from my fellow Filipino...its sad that a lot of them are not yet aware of how serious this problem is...i cant blame them for life and money is not easy for majority and living only on a hand to mouth existence..heathy living and diet, exercise, fresh fruits and leafy green fresh veggies is a good way to start the liver to heal on its own..will this really make a difference if u are chronic carrrier like me and all tests are still normal like sGPT/SGOT /HBV DNA pcr and ultra sound and LFT? is slightly diffuse fatty liver a start of a more serious problem wth HBV carrier? My doctor wont put me to medications and say i dont need to worry and fatty liver i need to take care of my diet and avoid foods that are oily. Many thanks..i am afraid even the doctors says am not in a worse situation.
Arrowhead is taking off as a stock on the back of ARC 520, many analysts are calling it a blockbuster. If phase 11a works DB thinks it has a 65% chance of a potential cure based on the profits they are forecasting for it. 5 billion a year.
Would be fantastic for all involved to have a legitimate cure
Would be fantastic for all involved to have a legitimate cure
They say "functional cure" Meaning it will be immune controlled. But it won't wipe out the cccdna so in other words its a potential treatment. In my view REP9AC' has more promise but Arrow Head have more funds than Replicor so we won't receive the best due to money. As ever "greed" rules health!
Arrowhead Receives Regulatory Approval to Begin Phase 2a Trial of Chronic Hepatitis B Candidate ARC - 520. People in Hong Kong can apply to join.
ARC 520 + entecavir
Link : http://www.businesswire.com/news/rxtimes/20140303005591/en/Arrowhead-Receives-Regulatory-Approval-Phase-2a-Trial
ARC 520 + entecavir
Link : http://www.businesswire.com/news/rxtimes/20140303005591/en/Arrowhead-Receives-Regulatory-Approval-Phase-2a-Trial
Just like Rep9 AC, probably combine with ETV or TDF to realize the clearance of HBsAg, after that, interferon or vaccine may be needed for anti-body growth.
Personally, I also have strong hope of ARC520. No thing but 1 shot to knock down over 95% HBsAg titer. Even it's just on a chimpanzee, it's still amazing.
Personally, I also have strong hope of ARC520. No thing but 1 shot to knock down over 95% HBsAg titer. Even it's just on a chimpanzee, it's still amazing.
Personally, I have very high hope of ARC520. I hope it will cure on its own, but I think eventually it will need to work in combination with an antiviral + an immune modulator such as Interferon or therapeutic vaccine.
This is interesting. Seem to be just a single injection of ARC520. Hopefully, this will identify an effective dose level. Further trials can then determine how many injections may be needed.
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