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Arrowhead Pharmaceuticals Presents Promising ARC-520 Hepatitis B Data at The Intern
What is our hope those with Hbeag - ?
Overall I think there is progress in this space and I feel big pharmas will continue to look for better results. Just one hour ago Merck released a comparison of ZEPATIER and Sofosbuvir + PegIFN/RBV for treatment of hcv. I'm not an expert but 100% cure rate with no effects was reported. With that said, once the cure for hbv is announced, other pharmas will continue to develop new and more effective drugs and prices will go down in a relatively short period of time. I feel we will get there very soon. Stay positive everybody!
ARC-520 produces deep and durable knockdown of
viral antigens and DNA in a phase II study in patients
with chronic hepatitis B
Chronic hepatitis B (CHB) has become an important target
for drug development. ARC-520 (ARC), the first RNA interference-based
drug to reach patients (pts), targets ccc-DNA-derived
mRNA; herein we report results in CHB. Methods: 58
CHB pts (48 ARC, 10 placebo (PL), mean age 41 yrs (range
23-59) were included. 38 pts were HBeAg-neg and 20 HBeAgpos.
At entry, 32 of 38 HBeAg-neg and 14 of 20 HBeAgpos
had taken entecavir (ETV) for mean of 5 yrs (range 2-8)
and were on ETV throughout the study. 12 treatment naïve pts
(6 HBeAg-neg, 6 HBeAg-pos) started on ETV during the trial.
All pts received a single dose IV of ARC or PL (6 HBeAg-pos
received a divided dose of ARC separated by 2 wks) and
had viral parameter knockdown (KD) measured over 85 days
[qHBsAg, HB core-related antigen (qHBcrAg) and viral DNA in
all, qHBeAg in HBeAg-pos]. Doses were 1-4 mg/kg in HBeAgneg.
All HBeAg-pos received 4 mg/kg. 15 pts are continuing
in follow-up. Results: ARC therapy was well tolerated - 23%
reported a mild or mod adverse event (AE) with no AE rated
serious, severe, drug-related or causing withdrawal from the
trial. Viral DNA was below level of quantitation in all chronic
ETV pts at study entry. Naïve pts reduced viral DNA up to 4.3
log (mean 2.2 log) after ARC and ETV. ARC reduced viral
antigens with qHBeAg best KD of 1.7 log (mean max 1.2 log)
following a single 4 mg/kg dose. In naïve pts, best qHBsAg
KD of 1.9 log (mean max 1.1 log) in HBeAg-pos and 0.7 log
(mean max 0.2 log) in HBeAg-neg were observed. qHBcrAg
showed a dose response in HBeAg-neg with best KD at 1 mg/
kg of 0.18 log (mean max 0.15 log) and 1.1 log (mean max
0.9 log) with 4 mg/kg. HBeAg-pos showed best KD of 1.1 log
(mean max 0.92 log). The qHBsAg dose response was less
deep in chronic ETV pts with best observed reduction of 0.3
log (mean max 0.2 log) observed at 1 mg/kg vs 0.5 log (mean
max 0.4 log) at 4 mg/kg in HBeAg-neg. Best qHBsAg KD in
chronic ETV treated HBeAg-pos was 0.7 log (mean max 0.3
log). Divided doses at 4 mg/kg did not increase antigen KD.
Duration of qHBsAg KD was typically 8 wks with 2 distinct KD
patterns of qHBsAg seen: an immediate, direct ARC antiviral
effect (~70% of pts) and a delayed response several weeks
after treatment (~30% of pts). Conclusions: 1) These findings
are consistent with more cccDNA-driven antigen production
in HBeAg-pos. 2) ARC was well tolerated 3) ARC effectively
inhibited cccDNA-derived mRNA with protein KD up to 1.9
logs (99%) observed 4) These variations in viral protein KD are
consistent with ARC data in chimps and previously reported
chronic ETV reductions in pts for cccDNA 5) Chronic ARC studies
aimed at producing HBsAg seroclearance are underway.
viral antigens and DNA in a phase II study in patients
with chronic hepatitis B
Chronic hepatitis B (CHB) has become an important target
for drug development. ARC-520 (ARC), the first RNA interference-based
drug to reach patients (pts), targets ccc-DNA-derived
mRNA; herein we report results in CHB. Methods: 58
CHB pts (48 ARC, 10 placebo (PL), mean age 41 yrs (range
23-59) were included. 38 pts were HBeAg-neg and 20 HBeAgpos.
At entry, 32 of 38 HBeAg-neg and 14 of 20 HBeAgpos
had taken entecavir (ETV) for mean of 5 yrs (range 2-8)
and were on ETV throughout the study. 12 treatment naïve pts
(6 HBeAg-neg, 6 HBeAg-pos) started on ETV during the trial.
All pts received a single dose IV of ARC or PL (6 HBeAg-pos
received a divided dose of ARC separated by 2 wks) and
had viral parameter knockdown (KD) measured over 85 days
[qHBsAg, HB core-related antigen (qHBcrAg) and viral DNA in
all, qHBeAg in HBeAg-pos]. Doses were 1-4 mg/kg in HBeAgneg.
All HBeAg-pos received 4 mg/kg. 15 pts are continuing
in follow-up. Results: ARC therapy was well tolerated - 23%
reported a mild or mod adverse event (AE) with no AE rated
serious, severe, drug-related or causing withdrawal from the
trial. Viral DNA was below level of quantitation in all chronic
ETV pts at study entry. Naïve pts reduced viral DNA up to 4.3
log (mean 2.2 log) after ARC and ETV. ARC reduced viral
antigens with qHBeAg best KD of 1.7 log (mean max 1.2 log)
following a single 4 mg/kg dose. In naïve pts, best qHBsAg
KD of 1.9 log (mean max 1.1 log) in HBeAg-pos and 0.7 log
(mean max 0.2 log) in HBeAg-neg were observed. qHBcrAg
showed a dose response in HBeAg-neg with best KD at 1 mg/
kg of 0.18 log (mean max 0.15 log) and 1.1 log (mean max
0.9 log) with 4 mg/kg. HBeAg-pos showed best KD of 1.1 log
(mean max 0.92 log). The qHBsAg dose response was less
deep in chronic ETV pts with best observed reduction of 0.3
log (mean max 0.2 log) observed at 1 mg/kg vs 0.5 log (mean
max 0.4 log) at 4 mg/kg in HBeAg-neg. Best qHBsAg KD in
chronic ETV treated HBeAg-pos was 0.7 log (mean max 0.3
log). Divided doses at 4 mg/kg did not increase antigen KD.
Duration of qHBsAg KD was typically 8 wks with 2 distinct KD
patterns of qHBsAg seen: an immediate, direct ARC antiviral
effect (~70% of pts) and a delayed response several weeks
after treatment (~30% of pts). Conclusions: 1) These findings
are consistent with more cccDNA-driven antigen production
in HBeAg-pos. 2) ARC was well tolerated 3) ARC effectively
inhibited cccDNA-derived mRNA with protein KD up to 1.9
logs (99%) observed 4) These variations in viral protein KD are
consistent with ARC data in chimps and previously reported
chronic ETV reductions in pts for cccDNA 5) Chronic ARC studies
aimed at producing HBsAg seroclearance are underway.
2 Comments
I'd like to know just what the adverse effects were that they experienced. Anyone have a list?
Thanks Sorte for posting this very encouraging news. I think we are getting ever closer to the magical at least functional cure.
Gilead Announces Full 48-Week Results From Two Phase 3 Studies Evaluating Tenofovir Alafenamide (TAF) for Patients With Chronic Hepatitis B Infection
http://www.hcplive.com/conference-coverage/easl-2016/novel-drug-for-hepb-and-hepd-clears-treatment-hurdle
http://investor.arbutusbio.com/releasedetail.cfm?ReleaseID=965036
Arbutus Presents Data on HBV Capsid Assembly Inhibitor AB-423 at EASL 2016
VANCOUVER, British Columbia and DOYLESTOWN, Pa., April 14, 2016 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq:ABUS), an industry-leading Hepatitis B Virus (HBV) therapeutic solutions company, presented preclinical combination data on its potent core protein/ capsid assembly inhibitor, AB-423, at the European Association for the Study of the Liver (EASL) in Barcelona, Spain.
"We are excited to present data supporting combination of our lead core protein/capsid assembly inhibitor, AB-423, with a nucleoside analog, entecavir (EVT). AB-423 in combination with EVT has shown synergistic antiviral activity in vitro in primary human hepatocytes. Furthermore, AB-423 alone and in combination with entecavir has shown potent in vivo activity in a hydrodynamic injection (HDI) mouse model of HBV," said Dr. Mark J. Murray, Arbutus' President and CEO. "We are focused on advancing the development of our proprietary HBV candidates, including AB-423, to enable one or more clinical HBV combination studies in 2017. Additional data from our preclinical combination studies will be presented at upcoming scientific conferences."
The presentation is titled "In Vitro and In Vivo Antiviral Activities of AB-423 a Potent Small Molecule Inhibitor of Hepatitis B Virus Capsid Assembly", and a copy of the poster can be accessed by visiting the Investor sections of www.arbutusbio.com and selecting Events and Presentations.
Arbutus Presents Data on HBV Capsid Assembly Inhibitor AB-423 at EASL 2016
VANCOUVER, British Columbia and DOYLESTOWN, Pa., April 14, 2016 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq:ABUS), an industry-leading Hepatitis B Virus (HBV) therapeutic solutions company, presented preclinical combination data on its potent core protein/ capsid assembly inhibitor, AB-423, at the European Association for the Study of the Liver (EASL) in Barcelona, Spain.
"We are excited to present data supporting combination of our lead core protein/capsid assembly inhibitor, AB-423, with a nucleoside analog, entecavir (EVT). AB-423 in combination with EVT has shown synergistic antiviral activity in vitro in primary human hepatocytes. Furthermore, AB-423 alone and in combination with entecavir has shown potent in vivo activity in a hydrodynamic injection (HDI) mouse model of HBV," said Dr. Mark J. Murray, Arbutus' President and CEO. "We are focused on advancing the development of our proprietary HBV candidates, including AB-423, to enable one or more clinical HBV combination studies in 2017. Additional data from our preclinical combination studies will be presented at upcoming scientific conferences."
The presentation is titled "In Vitro and In Vivo Antiviral Activities of AB-423 a Potent Small Molecule Inhibitor of Hepatitis B Virus Capsid Assembly", and a copy of the poster can be accessed by visiting the Investor sections of www.arbutusbio.com and selecting Events and Presentations.
,
I just read the current post on arrowhead presentations. With due respect fox, can you thrown more clarity on this statement.
"and all HBeAg negative, treatment naïve patients achieving reductions that put them below the limit of quantitation" and what is the significant difference between ARc520 effectiveness on hbeAg+ and hbeAg-
Thanks
I just read the current post on arrowhead presentations. With due respect fox, can you thrown more clarity on this statement.
"and all HBeAg negative, treatment naïve patients achieving reductions that put them below the limit of quantitation" and what is the significant difference between ARc520 effectiveness on hbeAg+ and hbeAg-
Thanks
Liverpatient I agree with you. I've went onto the website there definitely is hope. I feel we are getting closer to cure :-)
It seems that the only serious event happened to 1 out of 48 patients who got a 'complete heart block'. He had a pre-existing heart condition (but not a 'complete heart block') that was missed on a pre-screening ECG. The 'complete heart block' seem to be resolved after the medicine was stopped.
For CHB hbeag negative, administration of 2 mg/kg doses, with which they are running their crucial combo trial in Australia, reduced hbsag by 0.2 logs. This was a single administration, with a multiple administration this reduction increased to 0.3 logs as per their recently publicised research in Tokyo.
0.3 logs is equal to 50% of reduction...however this reduction is rather small and temporary (won't continue ARC administration is stopped).
Their hope is that this reduction will active the immune system and together with pegasys will help out wipe out hbssag
0.3 logs is equal to 50% of reduction...however this reduction is rather small and temporary (won't continue ARC administration is stopped).
Their hope is that this reduction will active the immune system and together with pegasys will help out wipe out hbssag
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