JAK consists of four intracellular non-receptor tyrosine kinases that help in cytokine mediated signaling through the JAK-STAT pathway. It contains two almost identical phosphate transferring domains in which one domain shows kinase activity and the other regulates the activity of the first via negative inhibition.
New York, NY -- (SBWIRE) -- 04/25/2019 -- JAK comprises four receptors JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2) which help in cytokine mediated signaling through the JAK/STAT pathway. There are two nearly identical phosphate transferring domains present in JAKs. The first domain demonstrates kinase activity while the other regulates the activity of the first via negative inhibition. The mutations in the JAK/STAT pathway leads to different medical conditions.
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The JAK inhibitors work by blocking the cytokine mediated signaling via JAK/STAT pathway which plays an important role in immune regulation and growth.The pipeline of JAK inhibitors is quite robust with drugs being developed in the Pre-Registration, Phase III, Phase II, Phase I, Pre-Clinical, and Discovery stage of development. Also, majority of the pipeline products are currently undergoing Phase II clinical studies.
According to the research findings, majority of the JAK inhibitors in the pipeline are being developed for oral administration. It has been observed that the oral route of medication is convenient, available in delayed or rapid release formulation, less risk of systemic infections, and inexpensive in nature, and also provides improved patient's compliance. Moreover, the drugs administered by this route are less invasive and can be modified for extended release, thereby increasing the bioavailability. Also, administration of JAK inhibitors through oral route have shown promising results in the clinical studies.
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The companies developing JAK inhibitors have shown positive clinical results in the various phases of drug development. For instance, in January 2018, LEO Pharma A/S's collaborator Japan Tobacco Inc. and Torii Pharmaceutical Co. Ltd. announced the topline results from delgocitinib's Phase III comparative study. The primary endpoints of the study were met and there were no clinically significant findings on safety and tolerability of delgocitinib within the treatment period. Similarly, Astellas Pharma Inc. in February 2018, announced results of two-Phase II trials on peficitinib wherein the drug demonstrated superiority over the placebo w.r.t the primary endpoints. Also, the safety profile of Peficitinib was found to be consistent.
In the wake of various strategic development activities, Theravance Biopharma Inc. and Janssen Global LLC signed an agreement in February 2018 to jointly develop and commercialize Phase I product, TD-1473. Similarly, Galapagos NV and Gilead Sciences Inc. in December 2015 signed a partnership agreement to develop and commercialize filgotinib for the treatment of rheumatoid arthritis and Crohn's disease. Therefore, collaborating and partnering with other companies can help the current players in the pipeline to expand their drug portfolio for the treatment of diseases related to the JAK/STAT pathway.
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Pfizer Inc., Eli Lilly and Company, Incyte Corporation, AbbVie Inc., Concert Pharmaceuticals Inc., Portola Pharmaceuticals Inc., Italfarmaco S.p.A, CTI BioPharma Corp., Theravance Biopharma Inc., Janssen Global LLC, and Galapagos NV are some of the companies involved in the development of JAK inhibitors.