Aa
CMX157 Data
ContraVir reports data shows CMX157 more potent against HBV than Gilead Viread
ContraVir Pharmaceuticals (CTRV) announced preliminary data dramatizing the unique properties of CMX157, the company's highly potent lipid prodrug of the successful antiviral drug tenofovir, or TFV. CMX157 was shown to be 60-fold more active than tenofovir against the hepatitis B virus, or HBV, based on in vitro studies. This significant potency difference has considerable potential in increasing the safety profile and reducing the side effects compared to tenofovir DF, or Gilead's (GILD) Viread. The company believes CMX157's lipid-conjugate design clearly differentiates it from tenofovir DF. ContraVir plans to file an investigational new drug, or IND, application for CMX157 to treat HBV before year-end 2015. CMX157 benefits from earlier human studies in volunteers under an IND for HIV. ContraVir is focused on a quick evaluation of CMX157 in a Phase 2 clinical study in patients with hepatitis B which it plans to begin in 2016. CMX157's enhanced absorption technology which utilizes the natural lipid uptake pathway to target the liver has the potential to lower systemic exposure compared to tenofovir, resulting in reduced off-target toxicity. Other studies with CMX157 are examining the efficiency of CMX157 prodrug conversion to the active antiviral, tenofovir diphosphate, within targeted hepatocytes, and further assessing the in vitro safety profile of CMX157, including a comprehensive evaluation of the likelihood of drug-drug interactions.
ContraVir Pharmaceuticals (CTRV) announced preliminary data dramatizing the unique properties of CMX157, the company's highly potent lipid prodrug of the successful antiviral drug tenofovir, or TFV. CMX157 was shown to be 60-fold more active than tenofovir against the hepatitis B virus, or HBV, based on in vitro studies. This significant potency difference has considerable potential in increasing the safety profile and reducing the side effects compared to tenofovir DF, or Gilead's (GILD) Viread. The company believes CMX157's lipid-conjugate design clearly differentiates it from tenofovir DF. ContraVir plans to file an investigational new drug, or IND, application for CMX157 to treat HBV before year-end 2015. CMX157 benefits from earlier human studies in volunteers under an IND for HIV. ContraVir is focused on a quick evaluation of CMX157 in a Phase 2 clinical study in patients with hepatitis B which it plans to begin in 2016. CMX157's enhanced absorption technology which utilizes the natural lipid uptake pathway to target the liver has the potential to lower systemic exposure compared to tenofovir, resulting in reduced off-target toxicity. Other studies with CMX157 are examining the efficiency of CMX157 prodrug conversion to the active antiviral, tenofovir diphosphate, within targeted hepatocytes, and further assessing the in vitro safety profile of CMX157, including a comprehensive evaluation of the likelihood of drug-drug interactions.
Here is another version of this report, that states that the comparator was not Tenofovir TFV, but actual Viread , that is tenofovir disoproxil fumarate or TDF. If this divergent version is true, then the new drug would have the potential for fundamental advantages over Viread and even over the newly developing TAF (Tenofovir alafenamide):
"CMX157, a novel lipid acyclic nucleoside phosphonate, “is up to 60-fold more active against HBV and more than 200-fold more active against all major HIV subtypes in vitro” compared with Viread (tenofovir disoproxil fumarate [DF], Gilead Sciences), according to the release. In a phase 1 clinical trial among healthy volunteers, CMX157 showed a favorable safety, tolerability and drug distribution profile. CMX157 decreased circulating levels of tenofovir, lowered systemic exposure and reduced the potential for renal and bone side effects."
Unfortunately, the reports by these financial advisors/reporters frequently lack the necessary precision. In this case the difference would be critical. I am not sure at this point what to trust, since in some presentations the company actually seemingly used simple Tenofovir, not TDF as a comparison drug.
"CMX157, a novel lipid acyclic nucleoside phosphonate, “is up to 60-fold more active against HBV and more than 200-fold more active against all major HIV subtypes in vitro” compared with Viread (tenofovir disoproxil fumarate [DF], Gilead Sciences), according to the release. In a phase 1 clinical trial among healthy volunteers, CMX157 showed a favorable safety, tolerability and drug distribution profile. CMX157 decreased circulating levels of tenofovir, lowered systemic exposure and reduced the potential for renal and bone side effects."
Unfortunately, the reports by these financial advisors/reporters frequently lack the necessary precision. In this case the difference would be critical. I am not sure at this point what to trust, since in some presentations the company actually seemingly used simple Tenofovir, not TDF as a comparison drug.
A misleading announcement. Taking advantage of the fact, that things are indeed a bit more complicated.
"CMX157 was shown to be 60-fold more active than tenofovir against the hepatitis B virus, or HBV, based on in vitro studies. "
That is actually not much better than tenofovir vs tenofovir disoproxil fumarate, the actual substance in Viread. It is 50 times more potent than tenofovir.
It is all this improper simplification of callling viread tenofovir.
Tenovovir, if it would be given orally, would have no effect on HBV.
TEnofovir if given intravenously or sc would still have almost no effect on HBV in the liver. the substance has a high negative charge and cannot easlily penetrate cell membranes. So it is not intestinally absorbed or uptaken by hepatocytes even if given parenterally.
the only cell type, that easily picks up tenofovir is the proximal tubulus cell in the kidney, which has a special anionic transporter, that will catch and bring this molecule to the inside, at high concentrations, when excreted in the glomerulus. That is the basis of vireads nephrotoxicity inclination, sinde Viread , which is tenofovir disoproxil fumarate ( TDF), falls apart rapidly in plasma, producing pure tenofovir, that goes to the kidney and is picked up there.
Nevertheless, while still intact, enough TDF enters the liver cells, where is it finally converted in several steps to tenofovir diphosphate, which is the actual substance that inhibits the viral polymerase.
this new drug seems to enter hepatocytes with relative ease, but still not as easy as tenofovir alafenamide ( TAF), the new Gilead drug currently in trials.
It is hard to predict if it would offer a better overall toxicity profile than the current viread, or even better as the upcoming TAF.
More pharmacokinetics studies in vivo are needed to know how it finally distributes in the human tissues.
And of course it is meant to be an oral drug.
"CMX157 was shown to be 60-fold more active than tenofovir against the hepatitis B virus, or HBV, based on in vitro studies. "
That is actually not much better than tenofovir vs tenofovir disoproxil fumarate, the actual substance in Viread. It is 50 times more potent than tenofovir.
It is all this improper simplification of callling viread tenofovir.
Tenovovir, if it would be given orally, would have no effect on HBV.
TEnofovir if given intravenously or sc would still have almost no effect on HBV in the liver. the substance has a high negative charge and cannot easlily penetrate cell membranes. So it is not intestinally absorbed or uptaken by hepatocytes even if given parenterally.
the only cell type, that easily picks up tenofovir is the proximal tubulus cell in the kidney, which has a special anionic transporter, that will catch and bring this molecule to the inside, at high concentrations, when excreted in the glomerulus. That is the basis of vireads nephrotoxicity inclination, sinde Viread , which is tenofovir disoproxil fumarate ( TDF), falls apart rapidly in plasma, producing pure tenofovir, that goes to the kidney and is picked up there.
Nevertheless, while still intact, enough TDF enters the liver cells, where is it finally converted in several steps to tenofovir diphosphate, which is the actual substance that inhibits the viral polymerase.
this new drug seems to enter hepatocytes with relative ease, but still not as easy as tenofovir alafenamide ( TAF), the new Gilead drug currently in trials.
It is hard to predict if it would offer a better overall toxicity profile than the current viread, or even better as the upcoming TAF.
More pharmacokinetics studies in vivo are needed to know how it finally distributes in the human tissues.
And of course it is meant to be an oral drug.
Is this an oral medication (I tried searching and couldn't find answer)? I can understand marketing for the potential of lower toxicity, but how is it more potent if it is just a prodrug of Tenofovir?
Have an Answer?
You are reading content posted in the Hepatitis B Community
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
