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Myrcludex
Spoke to Hepatera Moscow today, asked about the results of Myrcludex clinical trials started in December 2012 that were supposed to end in December 2013.
The reply was that early tests showed that the drug was well tolerated and the permission was gained to increase the dose and extend the time of the therapy transferring directly to phase 2. This phase will finish in September 2014 and the results will be available by the end of the year. Next stage will be phase 3 mass trial and in case of positive results we should expect the drug in the market in 2 - 3 years from now.
The reply was that early tests showed that the drug was well tolerated and the permission was gained to increase the dose and extend the time of the therapy transferring directly to phase 2. This phase will finish in September 2014 and the results will be available by the end of the year. Next stage will be phase 3 mass trial and in case of positive results we should expect the drug in the market in 2 - 3 years from now.
hbsag quantitative in iu/ml
if available hbeag quantitative too
if available hbcab igm quantitative
hbv genotype
hbvdna
all this needed to choose the best
if you are seroconverting and hbeag-hbvdna is low it can be ok to start with pegintf too
if available hbeag quantitative too
if available hbcab igm quantitative
hbv genotype
hbvdna
all this needed to choose the best
if you are seroconverting and hbeag-hbvdna is low it can be ok to start with pegintf too
Stef, I am 31 years old a male, born with HBV (E+ and S+). ALT/AST were all normal before. Recent 3 months my ALT is raising to 112, any recommendation on my therapy? Shall I take IFN or apply NUCs directly? I am planning to have a child within 1 year, so I am hesitate to IFN therapy.
with entecavir and tenofovir it was only 3 years, only the weak antivirals like lam and adv not used today were used for 7 years
tdf has 0% resistance
tdf has 0% resistance
Stefano, it's an amazing news.
By the way, 7 years TDF, is there any resistance rate of 7 years TDF therapy?
By the way, 7 years TDF, is there any resistance rate of 7 years TDF therapy?
yes the other 3 patients will clear hbsag by continuing nucs with very high probability (the values were very low from 20-100iu/ml) or by another round of peginterferon
the effect of peg should continue for 1-5 years and since they keep using nucs and they reached 20-100iu/ml they should clear in 1-5 years and they might even stop all therapies since hbv is totally inactive at that low hbsag
the effect of peg should continue for 1-5 years and since they keep using nucs and they reached 20-100iu/ml they should clear in 1-5 years and they might even stop all therapies since hbv is totally inactive at that low hbsag
Does is mean with 3~7 years NUCs and then 2 years IFN combo therapy, generally we can realize over 60% cure of HBV?
And the other 40% also have high likehood of cure subsequently?
And the other 40% also have high likehood of cure subsequently?
no it was the results of one the early trials with pegintf add on to longterm nucs
it was 3-7 years of nucs and then about 2 years of peg add on, the other 40% not clearing 3 reached very very low hbsag and one stopped peg after 24 weeks but had decline too
it was 3-7 years of nucs and then about 2 years of peg add on, the other 40% not clearing 3 reached very very low hbsag and one stopped peg after 24 weeks but had decline too
I was looking for something new on Myrc B and came across this
60% hbsag loss at 96 weeks? Is that a combo of Zocor, Tenoforvir and Peg?
60% hbsag loss at 96 weeks? Is that a combo of Zocor, Tenoforvir and Peg?
Good inf. .. nice discussion ..
if the side effects is not so much woth high dosage of myrcludex .. i hope they will expedite the trial to take shorter periods than the estimated current periods .. patients all over the world want to start take new cure medicine ..
if the side effects is not so much woth high dosage of myrcludex .. i hope they will expedite the trial to take shorter periods than the estimated current periods .. patients all over the world want to start take new cure medicine ..
i didn t know PN can be irreversible or correlated to mitochindrial damage, in this case it is best to avoid this drug totally
i thought PN could be something like what happens with statins and fully reversible, but if this is not the case it doesnt worth the risk
i thought PN could be something like what happens with statins and fully reversible, but if this is not the case it doesnt worth the risk
telbivudine has one important capacity that is different from the other nucs. Its main action is blocking of the plus strand synthesis, that occurs after the reinfecting virions core opens to allow completion of the single stranded portion of its genome. thus the time completing the double stranded genome post entry is substantially prolonged, which will lead in many cases to a destruction of the invading HBV DNA before its completion and conversion to the cccDNA. Thus many infection events are prematurely terminated.
In that sense it will cooperate well with tenofovir for additive action, or with interferon to partially block reinfection, speeding up clearance.
However the above mentioned potential side effects make it risky to try. It is not clear if the neuropathy is reversible at all. If not it might indeed reflect irreversible mitochindrial damage.
In that sense it will cooperate well with tenofovir for additive action, or with interferon to partially block reinfection, speeding up clearance.
However the above mentioned potential side effects make it risky to try. It is not clear if the neuropathy is reversible at all. If not it might indeed reflect irreversible mitochindrial damage.
The future seem gloom for HBVers from your analysis based on the available therapy whether applied mono or combo...
Lets wait for breakthrough soon.
Lets wait for breakthrough soon.
While telbivudine has this astounding kidney protecting effect, its propensity for neuropathy combined with the fact that it is not an obligate chain terminator makes it a non optimal candidate for a nuc combo. Tenofovir seems to have a truly minuscule tendency for resistance, but if one is worried nevertheless, then Entecavir seems a better choice to achieve that. Lam or FTC as in truvada are possible combos, less protective however than Entecavir. But both lam and FTC are obligated chain terminators and are therefore less likely to slowly introduce irreversible mutations into mitochondrial DNA.
Nucs will reduce mitochondrial DNA synthesis to a varying degree. But with obligate chain terminators we can assume a full rebound after stopping them.
But once the MIT DNA carries base exchanges, they will be propagated indefinitely. The degree to which this actually happens with the non obligate nucs has not been investigated. Maybe it is so minor that it does not matter.
Nucs will reduce mitochondrial DNA synthesis to a varying degree. But with obligate chain terminators we can assume a full rebound after stopping them.
But once the MIT DNA carries base exchanges, they will be propagated indefinitely. The degree to which this actually happens with the non obligate nucs has not been investigated. Maybe it is so minor that it does not matter.
some team in italy tried something similar but with very short time like 24weeks telbivudine mono and then peg interferon mono 1 year.there was some hbsag loss
what do you think of telbivudine plus tenofovir pretreatment for 1-3 year and then peginterferon add on?i ve seen few immune studies on immunological effect of telbivudine and it worths pretreatment in combo tdf to prevent resistance.
i think it worths at least 12-24 weeks combo with peg with close monitoring for PN, but of course i understand no doctor likes to risk
some team in italy tried something similar but with very short time like 24weeks telbivudine mono and then peg intf add mono.there was some hbsag loss
i think it worths at least 12-24 weeks combo with peg with close monitoring for PN, but of course i understand no doctor likes to risk
some team in italy tried something similar but with very short time like 24weeks telbivudine mono and then peg intf add mono.there was some hbsag loss
When a rapid clearance of infected cells as with ifn therapy, is combined with high dose entry blocking we might see an acceleration of cccDNA clearance and surface antigen reduction.
Thus far the high percentage clearance peg ifn trials have worked mainly in patients with a low starting level of surface antigen, indicating a beginning spontaneous preponderance of at least partially successful T cell action, probably based on epitope availability and Tcell clone availability. In this scenario, the extra stimulation and the improved presentation by immunoproteasomes induced by interferon can shift the equilibrium towards mostly elimination, with a permanent T memory set remaining to stabilize this status when in the presence of a surface antibody only local cluster growth of reinfection is possible.
I am afraid, that at a higher surface antigen level, indicating a less fortunate starting constellation, the percentage of stable seroconversion will be much lower. Figuratively speaking, interferon can only push something that is already in motion. Extending the treating time will certainly help and might be used in cases where ifn is well tolerated and the hbsag decline is reasonable promising.
Thus far the high percentage clearance peg ifn trials have worked mainly in patients with a low starting level of surface antigen, indicating a beginning spontaneous preponderance of at least partially successful T cell action, probably based on epitope availability and Tcell clone availability. In this scenario, the extra stimulation and the improved presentation by immunoproteasomes induced by interferon can shift the equilibrium towards mostly elimination, with a permanent T memory set remaining to stabilize this status when in the presence of a surface antibody only local cluster growth of reinfection is possible.
I am afraid, that at a higher surface antigen level, indicating a less fortunate starting constellation, the percentage of stable seroconversion will be much lower. Figuratively speaking, interferon can only push something that is already in motion. Extending the treating time will certainly help and might be used in cases where ifn is well tolerated and the hbsag decline is reasonable promising.
It will be very difficult to treat people for a prolonged time with the high dose needed for effective re entry blocking.
after seeing results of the sequential treatment nucs+peg add on 96weeks : 60% hbsag cleared and 40% with low hbsag 20-130iu/ml
if we apply to that winning schedule myrcludex (or very high dose ezetimibe), nitazoxanide 2.5g daily, we should see better results on that 40% with low hbsag.what do you think?
my guess is that myrcludex or nucs without peg cannot achieve any sustained hbsag loss whatsoever and like hcv combos it makes no sense trying combinations/doses without peg
So low dose will not work high dose is not tolerable, do you think that Myrcludex is a failure?
The new dose of 5 and 10mg sadly is still not going to work. 20 to 30mg are needed to block viral uptake by ntcp to the extent necessary to block even slow reinfection. At this dose however, the bile acids will rise to high levels with strong side effects. The re uptake of bile acids is a critical process with a high throughput, it does not tolerate blocking to a high degree.
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