Discussion in 'XMRV Testing, Treatment and Transmission' started by Kate_UK, Dec 13, 2010.
Just saw that myself. Seems to be hugely more effective in Vitro than the current HIV antiretrovirals that are available to us. Very exciting indeed. I wonder how long it takes for these trials to be concluded though with all going well?
Exciting news, indeed.
CMX157 is not really a new drug though:
So they took Tenofovir/Viread and spiced it up (a lot?).
Very exciting to see such works going on now.
This looks really interesting in that it not only works on retroviruses but looks like it is very effective on herpes viruses as well. Especially those hard to reach viruses. This could really solve a lot of the IRIS problems, where it's the secondary infections that kick your butt, especially when beginning treatment. Since so many of us have secondary infections this could potentially be a 1-2 punch all in one "oral" pill.
Chimerix's Antiviral CMX157 Demonstrates Positive Phase 1 Clinical Results With Favorable Pharmacokinetics, Safety and Tolerability
Exhibits Potent In Vitro Activity Against XMRV and Highly Resistant HIV
DURHAM, N.C., Dec. 13, 2010 /PRNewswire/ -- Chimerix, Inc., a pharmaceutical company developing orally-available antiviral therapeutics, today announced first-in-human Phase 1 clinical trial results for CMX157 demonstrating a favorable safety, tolerability and drug distribution profile. In addition, results from a series of preclinical studies showed that CMX157 exhibited highly potent in vitro activity against human immunodeficiency virus (HIV), including HIV strains resistant to current therapies, and potent in vitro activity against xenotropic murine leukemia virus-related virus (XMRV), a blood-borne retrovirus recently associated with chronic fatigue syndrome (CFS).CMX157 clinical and preclinical findings were presented in an oral abstract, titled "CMX157 (HexadecyloxypropylTenofovir), a Clinical Stage Antiretroviral with In Vitro Activity against HIV and XMRV" at the HIV DART™ 2010 Frontiers in Drug Development for Antiretroviral Therapies conference.
"CMX157's promising safety profile and efficient conversion to the active drug in peripheral blood mononuclear cells, coupled with the potent in vitro antiviral activity across diverse drug-resistant strains of HIV, indicate that this compound may directly address the limitations of current HIV therapies," said Randall Lanier, Ph.D., Senior Director of Virology of Chimerix. "We are also excited about CMX157's in vitro antiviral activity against XMRV, a retrovirus recently associated with chronic fatigue syndrome."
"Our CMX001 and CMX157 programs are producing compelling clinical and preclinical evidence of how Chimerix's PIM Conjugate Technology transforms the way compounds are absorbed, distributed, metabolized and excreted, creating new agents with improved antiviral action and reduced toxicities. The promising clinical and preclinical data being reported for CMX157 strengthen our commitment to advancing this novel antiviral for the treatment of HIV and other applications, including its potential to address XMRV associated with chronic fatigue syndrome," said Kenneth I. Moch, President and Chief Executive Officer of Chimerix. "We believe CMX157 holds promise as a highly competitive anti-HIV agent, suitable for combination regimens, with a favorable pharmacokinetic and tolerability profile, and potential for once-weekly dosing. Further, we have intriguing in vitro data showing our PIM Conjugate Technology may facilitate CMX157 access across the blood-brain barrier to address latent retrovirus in compartments that otherwise have proven to be inaccessible by conventional anti-HIV agents. There's a significant need for new HIV therapies to help refractory and inadequately treated patients, and our next step is to evaluate CMX157 in HIV patients."
CMX157 Phase 1 Clinical Trial Results
CMX157 is a new chemical entity created by applying Chimerix's PIM (Phospholipid IntramembraneMicrofluidization) Conjugate Technology to chemically modify tenofovir, the molecule underlying the prodrug Viread, an antiviral agent approved for the treatment of human immunodeficiency virus (HIV) and chronic hepatitis B. The CMX157 Phase 1 clinical study was a randomized, blinded, dose-escalation trial to evaluate safety, tolerability and pharmacokinetics. Healthy volunteers received a single dose ranging from 25 mg to 400 mg of CMX157 or a standard dose of Viread for comparison of intracellular levels of the active antiviral, tenofovirdiphosphate (TFV-PP). CMX157 was well tolerated and there were no laboratory, vital sign, electrocardiogram changes or adverse event trends attributable to drug. In addition, plasma concentrations of CMX157 increased linearly with dose and target plasma levels were attained. The active antiviral, TFV-PP, was measurable in peripheral blood mononuclear cells (PBMC) from all patients after a single 400 mg dose of CMX157. PBMC levels of TFV-PP remained detectable for six days after the single 400 mg dose of CMX157, suggesting the possibility of a convenient, once-weekly dosing regimen.
CMX157 In Vitro Activity
The in vitro antiviral activity of CMX157 was evaluated in PBMCs for wild-type and nucleotide reverse transcriptase inhibitors (NRTI)-resistant HIV strains. CMX157 was effective and highly potent against all clinically-important HIV strains, including drug resistant isolates that are known to be unresponsive to tenofovir. CMX157 was observed to have highly potent antiviral activity against XMRV in vitro, with an EC50 approximately 20-fold more potent than the anti-retroviral drug azidothymidine (AZT) and 800-fold more potent than tenofovir. Data were also presented that showed CMX157 is not a substrate in vitro for human Organic Anion Transporter 1 (hOAT1), which actively transports tenofovir into renal proximal tubule cells of the kidney and is linked to tenofovir-induced nephrotoxicity. Consequently, CMX157 has significantly reduced potential to cause nephrotoxicity.
CMX157 findings were featured in an oral presentation, CMX157 (Hexadecyloxypropyl Tenofovir), a Clinical Stage Antiretroviral with In Vitro Activity against HIV and XMRV, by Randall Lanier, Ph.D., Senior Director of Virology of Chimerix, at the HIV DART 2010 Frontiers in Drug Development for Antiretroviral Therapies conference. A copy of Dr. Lanier's oral presentation and poster are available on the Chimerix website at www.chimerix.com.
CMX157 is a new chemical entity created by applying Chimerix's PIM (Phospholipid Intramembrane Microfluidization) Conjugate Technology to chemically modify tenofovir, marketed as the prodrug Viread, an antiviral agent approved for the treatment of HIV and chronic hepatitis B. Chimerix's proprietary PIM Conjugate Technology is being employed to improve the absorption and distribution profile of tenofovir, with the goal of increasing antiviral efficacy while decreasing potential toxicity. Chimerix is developing CMX157 for the treatment of patients who are refractory to or not sufficiently treated by existing HIV therapies.
Chimerix is developing novel antiviral therapeutics with the potential to transform patient care in multiple settings, including transplant, oncology, acute care and global health.
The company's lead candidate, CMX001, is in Phase 2 clinical studies in immunocompromised transplant and cancer patients for the treatment of life-threatening viruses, including cytomegalovirus and adenovirus. Over 325 people have received CMX001 to date. CMX001 has been well tolerated in all studies, with a growing body of evidence of the compound's antiviral activity in humans. In Chimerix's ongoing placebo-controlled studies, CMX001 has been administered to more than 200 patients and healthy volunteers. In addition, at the request of leading physicians at over 45 medical centers throughout the United States, Canada, Europe and Israel, CMX001 has been administered to more than 125 patients under investigator-held Emergency Investigational New Drug applications (EINDs) for the treatment of a wide range of infections caused by dsDNA viruses for which there are either no approved treatments or where patients have failed the available treatment. To date, CMX001 has been used to treat patients with 12 different dsDNA viral infections across all five families of dsDNA viruses that affect humans. CMX001 is also being developed as a medical countermeasure in the event of a smallpox release. Chimerix has received significant funding from the National Institutes of Allergy and Infectious Disease to develop CMX001 for smallpox.
Chimerix's second clinical-stage antiviral compound, CMX157, has completed Phase 1 clinical studies. CMX157 is in development as a potent nucleoside analogue against multi-drug resistant HIV infections.
Led by a world-class antiviral drug development team, Chimerix is also leveraging the company's extensive chemical library to pursue new treatments for hepatitis C virus, malaria and other global public health needs. For additional information on Chimerix, please visit http://www.chimerix.com.
SOURCE Chimerix, Inc.
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You know what I think is interesting. They mentioned XMRVs relationship to chronic fatigue syndrome (twice) but did not mention prostate cancer at all. Maybe this shows that a change in the way our illness is viewed is finally beginning.
I noticed that as well and was quite pleased
Phase I trials are just the phase where they determine safety, whether the drug is absorbed properly, etc. They are not even done on sick people, but on healthy volunteers (with rare exceptions.) It's a long way from there to a drug being available on the market. Here is an explanation of the phases of clinical trials:
woo hoo! thanks for posting this...sorely needed hope again today. i particularly liked the BBB penetration!!
diesel...unless you are a doctor, i dont think you can get the drug until its approved...
That's going to take years then
I hate this snail's pace everything seems to be moving at. It must even be more frustrating for the people that have been ill for decades. You can feel your life slipping through your hands. But I guess at least now things do seem to move a lot faster than a few years ago.
maybe they will fast track something for us...?
However, notice that the following sentence might be confusing:
At first glance, when I saw "800-fold more potent than tenofovir", I tought "Wow! Wow!!!". But then, when I looked at Dr. Singh's study about antiretrovirals against XMRV, I noticed that she checked among those antiretrovirals two drugs that are relevant here: One is tenofovir (TNV) - and tenofovir's EC50 is 82.9, or in other words very bad and very very very far from being effective enough against XMRV; The other one is "tenofovir disoproxil fumarate (TDF)" - and that's what I've been calling until now "tenofovir", as the drug that proven effective against XMRV in vitro. TDF's EC50 was 0.24 - very nice effectivity against XMRV in vitro.
So, the new drug, CMX157 seems to be very effective against XMRV in vitro, because it's EC50 should be aroung 0.11(AZT's EC50 against XMRV in vitro):20=0.0055, which is very similar to Raltegravir EC50 against XMRV in vitro (which is 0.005). But, it doesn't seem to be more effective than raltegravir in vitro, although they mention that it might be able to reach the brain effectivley - and I don't know if the existing antiretrovirals effective against XMRV do that (and don't know that they don't).
I can see this company being inundated with volunteers to be included in phase II or III. It is fantastic news! Thank you for posting it, I'm beginning to believe my 50yr nightmare will soon be over.
is there any new news on this med CMX 157?
"Last month the parents of a 7-year-old boy did just that and made headlines around the world. Josh Hardy's parents took to Twitter and Facebook when the drug company Chimerix denied their request for an experimental antiviral drug to save Josh's life. After receiving death threats from "Josh's army" -- executives had to hire security guards -- Chimerix reversed its position and granted Josh and other patients like him access to the drug.
Now that he's had the medicine, the virus that nearly killed Josh is gone and he's been moved out of the intensive care unit."
Merck Acquires CMX157 and EFdA and Starts Phase 2 Study for New NNRTI
By Simon Collins
On 24 July 2012, a press release from Merck announced that the company had signed licensing agreement for the development of two new nucleoside analogues and is about to launch a phase 2 study for its in house NNRTI.1
CMX157 is a nuceloside analogue in development at Chimerix that reported promising phase 1 results over four years ago and has been waiting for a financial backer since.2 The compound is a prodrug of tenofovir (tenofovir diphosphate as the active moiety), with an improved pharmacokinetic profile to tenofovir and initial results suggesting a potential for once-weekly dosing. The in vitro resistance profile includes sensitivity to K65R with some but not all thymidine analogue mutations. This was a compound that was expected to be picked up several years ago.
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