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Interleukin-6 Inhibitors Therapeutics Pipeline a Solution to Various Diseases

07-17-2019 01:49 PM CET | Health & Medicine

Press release from: Pharma Proff

Interleukin-6 Inhibitors Therapeutics Pipeline a Solution

Interleukin-6 (IL-6), an inflammatory cytokine involved in various biological processes, ranging from immune system activation and hematopoiesis to inflammation and regulating oncogenesis by taking part in gene activation and cell proliferation, survival, and differentiation. The receptor for this ligand (IL-6) is composed of two subunits — an alpha subunit responsible for ligand specificity, and glycoprotein (GP) 130, a receptor that other cytokines in the IL-6 family share. The Ras-mediated and Janus kinase (JAK)–Signal Transducers and Activators of Transcription (STAT) pathways are activated because of the IL-6 ligand and its receptor binding. 

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STAT3 and SHP2 [SH2 (Src Homology-2) Domain-containing Tyrosine Phosphatase] factors are phosphorylated by activated JAKs. The phosphorylated STAT3 forms a dimer and moves into the nucleus, where it activates the gene transcription of STAT3 response elements. These elements are important for G1-to-S-cell-cycle-transition signals and GP130-mediated cell survival. As the dysregulation of IL-6 signaling pathway leads to various cancers and dysimmune diseases, many anti-IL6 therapies are being developed. “Masked” antibodies, which are activated by disease-associated proteases, were recently developed by CytomX Therapeutics Inc. Similarly, Atlizumab (tocilizumab), an anti-IL6R monoclonal antibody (mAB), has also been tested for dysimmune diseases.

IL-6 Inhibitors Therapeutics Pipeline Driver

Technological advancements have made it possible for pharmaceutical companies to develop better drug candidates in the IL-6 inhibitors therapeutics pipeline. These advancements have helped in developing drugs to be given as either single therapy or combination therapies. The development of specific target therapies with better drug delivery mechanisms has become possible because of this. For instance, one of BIOCAD’s drug candidates, BCD 089 is being developed using the BonMab technology platform for autoimmune disorder treatment.

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Owing to the several benefits offered by the subcutaneous mode of drug administration, such as sustained and complete drug absorption, many companies are developing drugs to be given this way.  Vasoconstrictors, when administered subcutaneously, decrease the absorption of anesthetic agents, thereby prolonging its effect.

IL-6 Inhibitors Therapeutics Pipeline

The IL-6 inhibitors therapeutics pipeline was analyzed based on phase, route of administration, and molecule type. Based on phase, one among the total 18 drug candidates was in the Filed stage as of November 2017. Two drug candidates were in the phase III stage, five in Phase II, and one in the Phase I stage. Further, six candidates were in the pre-clinical stage and three in the discovery stage of development.

Sirukumab, the drug in the filed stage of the Interleukin-6 inhibitors therapeutics pipeline, is being developed by GlaxoSmithKline PLC in collaboration with Janssen Biotech Inc. It was also under Phase II development for severe asthma and in Phase III stage for giant cell arteritis. IL-6 is involved in many autoimmune conditions, such as rheumatoid arthritis (RA), therefore to target it, the drug candidate is being developed as a human monoclonal immunoglobulin G-1 (IgG1) kappa antibody and IL-6 inhibitor, to be administered subcutaneously.

For the treatment of RA, a drug being developed by R-Pharm Group — Olokizumab — was under Phase III development stage of the IL-6 inhibitors therapeutics pipeline. Its development is supported by the Nasonova Research Institute of Rheumatology, a leading Russian rheumatoid arthritis research institute. It is a humanized mAB that neutralizes GP-130 signaling by blocking the receptor signaling of the IL-6 complex. This drug was originally developed by a Belgian biopharmaceutical company, UCB Pharma S.A., which later gave the exclusive worldwide license to R-Pharm Group.

With the involvement of IL-6 signaling pathway in the development of various diseases, the therapeutics pipeline for IL6 inhibitors is set to experience growth in coming years.

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