Concert Pharmaceuticals is currently running a phase 1 pharmacodynamics (PD) clinical trial, before heading into a phase 2 clinical trial for patients with moderate to severe Alopecia Areata. The goal of the (PD) part of the phase 1 trial, will test CTP-543's ability to affect downstream gene regulation similar to ruxolitinib, with results in Q1 2017. Ruxolitinib which is already an FDA approved drug for various cancer indications has been tested for it's ability to affect downstream gene regulation STAT3. The results for ruxolitinib are below, and which can also be found in this link JAKAVI-ruxolitinib.
Pharmacodynamics
Ruxolitinib inhibits cytokine induced STAT3 phosphorylation in whole blood from healthy subjects and MF patients. Jakafi administration resulted in maximal inhibition of STAT3 phosphorylation 2 hours after dosing which returned to near baseline by 8 hours in both healthy subjects and myelofibrosis patients.
Metabolism
In vitro studies indicate that CYP3A4 is the major enzyme responsible for metabolism of ruxolitinib. Parent compound is the predominate entity in humans representing 60% of the drug-related material in circulation. The two major and active metabolites were identified in plasma of healthy subjects representing 25% and 11% of parent AUC. These metabolites have one-half to one-fifth of the parent JAK-related pharmacological activity. The sum of all active metabolites contribute to 18% of the overall pharmacodynamics of ruxolitinib.
Bottom Line: CTP-543 will be compared to the above ruxolitinib data, after completion of the current phase 1 clinical trial. The drug will be advancing into a phase 2 clinical trial for patients with moderate to severe Alopecia Areata, in the first quarter of 2017. CTP-543 is the deuterated version of ruxolitinib. Thank you for reading.
Pharmacodynamics
Ruxolitinib inhibits cytokine induced STAT3 phosphorylation in whole blood from healthy subjects and MF patients. Jakafi administration resulted in maximal inhibition of STAT3 phosphorylation 2 hours after dosing which returned to near baseline by 8 hours in both healthy subjects and myelofibrosis patients.
Metabolism
In vitro studies indicate that CYP3A4 is the major enzyme responsible for metabolism of ruxolitinib. Parent compound is the predominate entity in humans representing 60% of the drug-related material in circulation. The two major and active metabolites were identified in plasma of healthy subjects representing 25% and 11% of parent AUC. These metabolites have one-half to one-fifth of the parent JAK-related pharmacological activity. The sum of all active metabolites contribute to 18% of the overall pharmacodynamics of ruxolitinib.
Bottom Line: CTP-543 will be compared to the above ruxolitinib data, after completion of the current phase 1 clinical trial. The drug will be advancing into a phase 2 clinical trial for patients with moderate to severe Alopecia Areata, in the first quarter of 2017. CTP-543 is the deuterated version of ruxolitinib. Thank you for reading.
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