Janus kinase (JAK) inhibitors block Janus kinase activator enzymes and interrupt signaling pathway. It plays an important role in host defense, oncology, autoimmunity and hematological cancers, which makes them an important target for therapeutics. Many signal transduction pathways are done by JAK activity for the normal signaling. The abnormal aberration in JAKs activity can lead to diseased state. For instance, over activation of JAK can lead to tumorigenesis whereas loss of JAK can lead to severe combined immunodeficiency. Janus Kinases family contains JAK 1, JAK 2, JAK 3 and a group of cytoplasmic non-receptor Tyrosine kinases (NRTKs).
The cytokine receptor is associated with JAKs present on the surface of cells. JAK tyrosine kinase family are primarily associated with signal transduction originating from extracellular ligands, which often interact with transmembrane receptors. Different JAK tyrosine kinase are the key components in mediating signaling process such as expression of genes involved in proliferation, apoptosis, migration, and differentiation. They play a major role in immune defense as many signaling events involved in both innate and adaptive immunity is mediated by JAKs. They are also involved in cell growth, survival, development, and differentiation of immune cells. Mutation in JAKs leads to the immunodeficiency disorders.
The JAK inhibitors pipeline has more than 35 drugs. In pipeline analysis, drugs are analyzed on the basis of route of administration and molecule type. The pipeline is also analyzed on the basis of monotherapy and combination therapy, and different clinical phases including Phase III, Phase II, Phase I and Pre-Clinical stage.
Phase III clinical trial known for the comparison of new treatments with the standard treatment in which the safety, efficacy and side effects of new intervention is compared with the already existing treatment. The Phase III clinical trial takes around 2-3 years to complete and the total number of participants vary from 100-1,000. In JAK inhibitors, there are 6 drugs in Phase III clinical trial. For instance, baricitinib, an Eli Lilly & Company’s drug candidate is in Phase III for the treatment of rheumatoid arthritis.
Itacitinib, JAK inhibitors of Incyte Corporation has reached into Phase II clinical trial for the treatment of non-small cell lung cancer, primary myelofibrosis, post-polycythemia vera myelofibrosis and refractory Hodgkin lymphoma. Phase II clinical trial is the second Phase that answer safety, efficacy and dosing of the new intervention. It takes around 2 years to complete and between 100 – 120 patients participate in the Phase II trial.
Concert Pharmaceuticals is developing CTP-543, a Phase I drug candidate for alopecia areata. CTP-543 is an inhibitor of JAK1 and JAK2 involved in autoimmune disease. In Phase I clinical trial, safety of the new intervention is determined. The trial takes around 1-2 years to complete and the total number of volunteers participating in the trial vary between 15 – 30.
Aclaris Therapeutics, Inc. is developing ATI-50001, a pre-clinical drug candidate for the treatment of alopecia universalis and alopecia totalis. Pre-clinical study is also known as animal study. It is done before testing a drug in people to find out the toxicity profile of the drug. Pre-Clinical study is of two types, including In vitro and In vivo.
Pipeline analysis provides description about the key companies developing JAK inhibitor drugs. Some of the key players actively involved in the research and development are Galapagos NV, AbbVie Inc., Eli Lilly and Company, Gilead Sciences, Inc., Astellas Pharma Inc., CTI BioPharma Corp., Portola Pharmaceuticals, Inc., Japan Tobacco International, Incyte Corporation, Pfizer, Inc., and Asana BioSciences, LLC.