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Chimerix CMX001 disappointing results


mcmich

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Well it wasn't trialed on hsv in ppl was it? I hope they try that because it might just work for hsv but not for others. We've seen some drugs not work for their initial purpose but work very well for something else. 

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Was looking at getting a doctor to fill it off label if it had been approved in early 2016. Also, saw a study where this drug with Valtrex had a synergic effect. This combination therapy would have been a potential working cure driving the virus down to levels where it would be very difficult to infect someone, but obviously condom use would also be required.

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Yeah that'd be a great test. How much viral load and shedding reduction would they have and are they safe to use together? I hope the company checks it out for hsv. I mean the current antivirals are there for the taking. 

Edited by tom343
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23 hours ago, tom343 said:

Yeah that'd be a great test. How much viral load and shedding reduction would they have and are they safe to use together? I hope the company checks it out for hsv. I mean the current antivirals are there for the taking. 

They did check that in Mice.  The results were that taken in combination with acyclovir it reduced HSV shedding: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186990/

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Using both CMX001 and Acyclovir

At concentrations of 0.5 μM, CMX001 essentially eliminated the replication of viral DNA and reduced levels to below those associated with the inocula and was 100-fold more potent than ACV. "

Further down

"The improved efficacy afforded by these therapies suppresses virus replication to undetectable levels and minimizes the development of resistance "

Undetectable levels of virus replication would mean no detectable viral shedding. Basically a functional cure.....but would still use a condom to be safe!

 

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Cool drug with an interesting background/evolution.

it's interesting that a drug like this might not be in existence if it weren't for 9/11 catalyzing a demand to prep for bioterrorism.  And the evolution of the drug made it more bioavailable and safer than before.  The same additions they made to chimerix were released to Merck to be added to and enhance the HIV drug tenovir (sp?).

http://www.forbes.com/sites/davidkroll/2014/03/12/why-everyone-has-a-stake-in-the-chimerix-drug-offered-to-josh-hardy-cmx001-brincidofovir/

 

"Chimerix's  lead product candidate, brincidofovir, is an oral nucleotide analog that has shown broad-spectrum in vitro activity against all five families of DNA viruses that affect humans, including CMV, AdV, BKV and herpes simplex viruses."

http://ir.chimerix.com/releasedetail.cfm?releaseid=829247

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23 hours ago, mcmich said:

Using both CMX001 and Acyclovir

At concentrations of 0.5 μM, CMX001 essentially eliminated the replication of viral DNA and reduced levels to below those associated with the inocula and was 100-fold more potent than ACV. "

Further down

"The improved efficacy afforded by these therapies suppresses virus replication to undetectable levels and minimizes the development of resistance "

Undetectable levels of virus replication would mean no detectable viral shedding. Basically a functional cure.....but would still use a condom to be safe!

 

So then why does it say disappointing results?

The cynical part of me believes this drug will never  be released to fight HSV. It would just languish like that HPI inhibitor, something 316. 

 

Edited by Herbfresh
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Correct me if I'm wrong,  but did I just read correctly where  it said it was more potent than Acyclovir and eliminated the replication of the virus?  Why in the world would this be close to disappointing ?  Lol, oh man its  always some Bullshit with these companies when something is successful. Nothing new here. 

Edited by bayern77
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On December 31, 2015 at 6:23 PM, mcmich said:

Using both CMX001 and Acyclovir

At concentrations of 0.5 μM, CMX001 essentially eliminated the replication of viral DNA and reduced levels to below those associated with the inocula and was 100-fold more potent than ACV. "

Further down

"The improved efficacy afforded by these therapies suppresses virus replication to undetectable levels and minimizes the development of resistance "

Undetectable levels of virus replication would mean no detectable viral shedding. Basically a functional cure.....but would still use a condom to be safe!

 

Is this true data for HSV 

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1 hour ago, bayern77 said:

Correct me if I'm wrong,  but did I just read correctly where  it said it was more potent than Acyclovir and eliminated the replication of the virus?  Why in the world would this be close to disappointing ?  Lol, oh man its  always some Bullshit with these companies when something is successful. Nothing new here. 

So this drug won't be approved by FDA really they are crazy

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1 hour ago, bayern77 said:

Correct me if I'm wrong,  but did I just read correctly where  it said it was more potent than Acyclovir and eliminated the replication of the virus?  Why in the world would this be close to disappointing ?  Lol, oh man its  always some Bullshit with these companies when something is successful. Nothing new here. 

Brincidofovir is not being (or planned to be) tested for HSV suppression in a human trial.  The phase III trial (with disappointing results) was specifically testing brincidofovir to prevent CMV infections in people who received bone marrow transplants.  There is a period before, and shortly after, a bone marrow transplant in which the recipient has no immune system (it's wiped out by chemotherapy). A reactivation of CMV is basically fatal in that period.  Brincidofovir was very effective a preventing CMV reactivation for the first 12 weeks but as soon as the recipients went off the drug (at week 13) CMV instantly reactivated and several of the people who had previously been on the drug died.

When it comes to HSV the idea is that once it's approved for CMV (and adenovirus) infection in cancer patients it would be available (off label) to anyone who could talk a doctor in to prescribing it to them.  There was a pre-clinical study (in mice) that showed it was very effective when used in combination with Acyclovir (this is the paper everyone keeps referencing) at suppressing shedding.  It's worth stating again that there is not (and will likely never be) a clinical trial in humans on brincidofovir's effect on Herpes.

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The drug was tested with Acyclovir. The two drugs have different modes but worked in a synergic fashion to drive HSV to undetectable levels. Only tested in animals (mice?) from what I read.

The phase 3 trials were for the drugs use against CMV, another double stranded dna virus that also belongs to the herpes virus group. Think there are 8 herpes viruses.....

 

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2 minutes ago, mcmich said:

The drug was tested with Acyclovir. The two drugs have different modes but worked in a synergic fashion to drive HSV to undetectable levels. Only tested in animals (mice?) from what I read.

The phase 3 trials were for the drugs use against CMV, another double stranded dna virus that also belongs to the herpes virus group. Think there are 8 herpes viruses.....

 

CMV is it more dangerous than HSV?

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3 hours ago, Terrell said:

CMV is it more dangerous than HSV?

CMV is something that is said to be with nearly everyone.   It's more easily suppressed than HSV.   But if you were to get an organ transplant and taking immune suppressing drugs then CMV can come out, unsuppressed and do its dastardly deeds.

If you took immune suppressing drugs then your HSV would breakout like crazy.

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So technically if you had cmv and hsv in that situation you would be royally screwed. But they probably pump acyclovir do they to control hsv since so many ppl have it?

Edited by tom343
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I'm sure they have a whole procedures and protocols mapped out for it.   This is an interesting read about the transplant , viral etc deal...

http://m.jac.oxfordjournals.org/content/45/6/729.full

 

jeez, just let me go if I get to that point.  I'll be praying, let some children be reading various spiritual texts to me.  It's wild to think that not only are people's lives relying on an organ donor but also relying on that particular donor's organ isn't carrying a parasite or virus. My goodness, I don't even want to think about the path of the gears of karma that lead crazy events like that to happen to people...

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So it could very well be a cure for HSV, but since it is not effective with CMV, it will never come out? Great. Thanks for not thinking about people sick with HSV even one bit. 

Honestly, there's no reason to think HSV meds is going to ever get better in our lifetimes. Just some chicken shit vaccines we all know won't do shit. 

 

Edited by Herbfresh
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2 hours ago, Herbfresh said:

So it could very well be a cure for HSV, but since it is not effective with CMV, it will never come out? Great. Thanks for not thinking about people sick with HSV even one bit. 

Honestly, there's no reason to think HSV meds is going to ever get better in our lifetimes. Just some chicken shit vaccines we all know won't do shit. 

 

Brincidofovir (formerly CMX-001) will not cure Herpes.  In fact brincidofovir is in the same class of drugs as the current anti-HSV medications (acyclovir, famvir, etc...) called nucleoside analogs (referred to in the lingo as Nukes).  These drugs work by being "activated" by a specific viral enzyme and then slowing DNA replication in those cells. 

Acyclovir and it's cousins are activated by an enzyme called HSV-tk.  Brincidofovir's active ingredient (cidofovir) is activated by a different enzyme that is common to more viruses (like CMV and adenovirus).  Cidofovir is simply a more broad spectrum nuke than acyclovir not more potent (and significantly more toxic). 

From a practical perspective brincidofovir would be taken as a booster to acyclovir/famvir/valtrex to slow replication of HSV in cells that lack (or are under-expressing) HSV-tk.  Taken alone brincidofovir likely wouldn't even work as well as acyclovir (since it's less specific) though you may be able to take a little less and take it a little less often since it's more bio-available. 

I'm not sure why, on the other hand, you're so down on the vaccines.  Genocea's latest data showed that 6 month efficacy was on the order of taking daily famvir.  It should work synergisticly with the current antivirals and there is a very good chance an uninfected partner could protect themselves by getting the injection before contracting HSV.  That seems like a win in my book.

Edited by StayingUpbeat
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All,

I have watched this stock and CMX-001 for several years now.  Yes the CMV failure was huge and the stock tanking sucked--but I still believe it will get approved for Adenovirus and Smallpox.  Then you could still get it off label if you had a really bad case, no other approved therapy worked, and you had a really sympathetic doctor.

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  • 2 months later...

Hello,

I found this thread and forum while searching for Chimerix-related discussion.

I was wondering if folks had seen the ASH 2015 brincidofovir poster, which deals with HSV. It is here: http://www.chimerix.com/wp-content/uploads/2015/11/ASH2015_HSV_Papanicolaou.pdf.

Separately, just wanted to update folks that while brincidofovir did indeed not meet the primary endpoint in the CMV trial, subsequent analysis of the data shows that this is because doctors thought patients had GVHD-induced diarrhea, while in fact they had brincidofovir-induced diarrhea. Instead of temporarily stopping brinci usage, some docs increased corticosteroid and other immunosuppressant use by huge amounts (corticosteroid 8x vs. placebo), which of course dramatically increased infection rates and did nothing to the diarrhea.

The company actually anticipated this and instituted a "SMMP" (safety management and monitoring plan), which calls for a temporary stoppage of prophylactic brinci use if the patient has signs of diarrhea, and if it does not subside after re-starting, a reduction in dosage. The SMMP was designed as a way to combat high levels of brinci-related diarrhea found in the P2, but some doctors (36%) did not follow it.

The company as of now (3/5/2016) still doesn't absolutely know why some docs did not follow SMMP, but it hypothesizes that, since the majority of patients were in teaching hospitals, there was high turnover that the company didn't anticipate, and new medical teams simply ignored or did not know about the SMMP. Initially, the company educated medical teams as to the SMMP's importance, but it simply didn't anticipate the high turnover rate.

Edited by agamemnus
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