JAK Inhibitors, Potential Market Opportunity & Clinical Pipeline Insights 2019

Janus kinase (JAK) inhibitors will block the Janus kinase activator enzymes and interrupt signaling pathway. It targets the process that leads to the production of the damaged DNA, which is playing the major role in the production of cancerous cells. Several signal transduction pathways have to be done by JAK activity for inducing normal signaling. The abnormal variation in JAKs activity can lead to a diseased condition. For example, overactivation of JAK can lead to tumorigenesis while the loss of JAK can lead to severe combined immunodeficiency. Janus Kinases family comprises of JAK 1, JAK 2, JAK 3 and also a group of cytoplasmic non-receptor Tyrosine kinases (NRTKs). Different JAK tyrosine kinases are the key elements to mediate signaling processes such as an expression of genes, which are involved in the process of proliferation, apoptosis, migration, and differentiation. They play an important role in immune defense action as many signaling events involved in innate and adaptive immunity is mediated by JAKs. Thus mutation in JAKs is leading to immunodeficiency disorders.

Market Overview

Janus kinase inhibitors have come out as one of the latest potential candidate and growth frontier by many of the scientific researchers involved in the research and development of targeted therapies and cancer drugs. The available JAK inhibitors are most highly focusing on the treatment of rare hematological malignancies including myelofibrosis, primary thrombocythemia, and Polycythemia Vera. Moreover, the continuous efforts of the researchers led to the detection of the JAK role in a wide range of solid tumors like lung cancer, prostate cancer, pancreatic cancer, breast cancer, ovarian cancer, colorectal cancer, gastrointestinal cancers, etc.

Currently, there exists only one Janus kinase inhibitors drug, which is commercially available in the market by the approval of Ruxolitinib. Although this drug is approved to treat rare hematological malignancies, but the occurrence rate of these cancers was shown to be increasing in the past years. Further, the lack of effective treatment for these cancers and greater survival rates of the patients after treatment with Ruxolitinib has aided the commercial success of Ruxolitinib. And 27 drugs are found to be in various clinical development phases. Most of the drugs are in Preclinical phase (13 Drugs) followed by the Phase-II (4 Drugs) clinical trials. It is found to have 6 drugs in Phase III clinical trials of JAK inhibitors. For example, baricitinib, an Eli Lilly & Company’s drug candidate is in Phase III for the treatment of rheumatoid arthritis. Incyte Corporation has reached Phase II clinical trial of Itacitinib JAK inhibitor to treat non-small cell lung cancer, primary myelofibrosis, post-polycythemia vera myelofibrosis and refractory Hodgkin lymphoma. 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. Aclaris Therapeutics, Inc. is developing ATI-50001, a pre-clinical drug candidate for the treatment of alopecia universalis and alopecia totalis. The Promising Candidates in the Clinical Pipeline includes Momelotinib, Lestaurtinib, Pacritinib, Tofacitinib, Ruxolitinib, Baricitinib.

More than 5 JAK inhibitors are expected to enter into the cancer therapeutic market in the next decade. Furthermore, the huge commercial success of the Ruxolitinib JAK inhibitor for myeloproliferative disorders further accelerated the development of more JAK inhibitors in the market. The development of JAK inhibitors has been so impressive and fastest in the past five years and thus expecting a great economic success of this class of drugs in the nearby future. Advances in research and technology will add to the development of JAK inhibitors. The development of more JAK inhibitors will not only provides benefits to the cancer therapeutic market but will also add a better life from cancers to the patients.

Key Developments

• In March 2019, Celgene announced that the US Food and Drug Administration (FDA) has accepted its new drug application (NDA) for fedratinib (JAK2 inhibitor) for Myelofibrosis and granted a Priority Review.


• In Feb 2019, AbbVie has announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review of its New Drug Application (NDA) for upadacitinib (JAK1-selective inhibitor) for the treatment of adult patients having moderate to severe rheumatoid arthritis.

Segmentation

This Pipeline research report segments the JAK inhibitors pipeline on the basis of therapies employed (combination therapy, and monotherapy + combination therapy), therapeutic modality (small molecules, and unknown), RoA (oral and unknown), drugs under development (discovery, pre-clinical, phase I, phase I/II, phase II, and phase III), and recruitment status (recruiting, active not recruiting, enrolling by invitation, and undisclosed).

In the pipeline, investigated single molecule is being used as both in monotherapy and combination therapy. Based on RoA, nearly 67% of the total therapeutics is being developed for oral administration where the drug is administered through a mouth cavity.

Some of the key players involved in the research and development of JAK inhibitor drugs include 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.