AbbVie, New Base II JAK inhibitorapproved on the same day to treat rheumatoid arthritis and bone marrow fibrosis, respectively

Inrebic, the first new drug for bone marrow fibrosis in nearly a decade,FDA approves inrebic treatment for patients with pre-intermediate-2 and high-risk (intermediate-2/high-risk) primary or secondary myeloblastiamyeloma fibrosis is a rare and serious bone marrow disease that disrupts the normal production of blood cells in the bodyThe patient's bone marrow is gradually replaced by fibrosis scar tissue, limiting the bone marrow's ability to produce blood cellsThe production of blood cells is transferred from the bone marrow to the spleen and liver, causing organ swellingPatients also experience symptoms such as extreme fatigue, shortness of breath, pain under the ribs, fever, night sweats, itching and bone painWhen bone marrow fibrosis occurs on its own, it is called primary bone marrow fibrosisSecondary bone marrow fibrosis occurs when too much red blood cell production (true erythema) or too much platelet production (primary platelet hyperplasia) evolves into bone marrow fibrosisCurrently, there is only one approved drug to treat bone marrow fibrosis, which was launched in 2011 with the JAK1/JAK2 inhibitor Jakafi (ruxolitinib)inrebic is an oral JAK2 and FLT3 inhibitor that inhibits the activity of wild and mutation-activated JAK2 protein kinasesInrebic is a JAK2-specific inhibitor that inhibits JAK1, JAK3 and TYK2 betterStudies have shown that abnormal activation of JAK2 is associated with bone marrow fibrosis and true red blood cell hyperplasiaIn in vitro and animal trials, Inrebic was able to block STAT3/5 phosphorylation and improve disease-related symptomsthe mechanism of action of Inrebic (Photo: Impact Biomedicine official website)this approval is based on the results of the phase 2 trial JAKARTA2 and the critical phase 3 trial JAKARTAA total of 608 patients were treated by Inrebic, of whom 459 had bone marrow fibrosis and 97 had been treated with ruxolitinibThe JAKARTA trial results showed that 37 percent of patients who had not been treated with JAK inhibitors had a spleen volume of 35 percent, and 40 percent of patients with a combined bone marrow fibrosis score improved by more than 50 percent, both of which were significantly better than the placebo group (1 percent and 9 percent, respectively) also, the RESULTS of the JAKARTA2 clinical trial showed that 55 percent of patients who developed resistance to ruxolitinib had a spleen shrink, suggesting that Inrebic could also be effective in these patients Dr John Hood, founder and CEO of Impact Biomedicines, the development of the new drug has been a mixed bag, and its clinical trials have been halted by the FDA because of serious complications Dr John Hood, founder of Impact Biomedicines, brought the drug back to life, and today's FDA approval marks the drug's success over the development finish line Pharmaceeist is also pleased to be able to provide partners with the ability to develop and promote the launch of the new drug (read today's push article for Inrebic's "Back to Death" research and development story) Rinvoq - the first approved JAK1 selective inhibitor
The FDA approved the listing of Rinvoq (upadacitinib) for the treatment of adult patients with moderate to severe active rheumatoid arthritis (active RA) These patients are poorly reactive or intolerant of methotrexate (MTX) The new drug is expected to be available in the U.S by the end of August Rinvoq's indications do not include patients who have not received MTX treatment rheumatoid arthritis, an autoimmune disease that affects about 23.7 million people worldwide The patient's immune system mistakenly attacks his or her joints, causing inflammation and thickening of the tissues in the joints, as well as damage to bones and associated connective tissue Symptoms such as pain, fatigue and joint stiffness in patients have a significant impact on their daily lives, and if not treated properly, rheumatoid arthritis can lead to permanent deactivation of bone and cartilage damage Rinvoq (upadacitinib) is a small molecule JAK1 selective inhibitor that is taken orally once a day In addition to treating rheumatoid arthritis, it is also clinically studied in a number of inflammatory indications, including psoriasis arthritis, Crohn's disease, ulcerative colitis, hypercyllathan scoliosis, and acursion dermatitis Rinvoq Molecular Structure (Photo: jmorris0x0 (CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)) this approval is based on the results of the SELECT clinical trial project This Phase 3 clinical study program consists of five clinical trials involving a total of nearly 4,400 patients In all SELECT Phase 3 clinical trials, Rinvoq reached all major endpoints and critical secondary endpoints The main endpoints include: SELECT-EARLY trial: In patients who did not receive MTX treatment, the group treated with Rinvoq reached ACR50 52% after 12 weeks (more than 50% improvement in RA symptoms according to the Standard Patients of the American Society of Rheumatology), and 28% of the MTX group SELECT-MONOTHERAPY trial: In patients treated with MTX, 68% of patients treated with Rinvoq reached ACR20 after 14 weeks, compared with 41% in patients who continued to use MTX SELECT-COMPARE trial: 71% of patients treated with Rinvoq-MTX reached ACR20, compared with 36% in the placebo-MTX patient group and, the results of these trials show that more than 30% of patients were able to enter clinical remission after receiving Rinvoq therapy At this time, the patient does not use MTX, there is little disease activity and symptoms The duration of the clinical remission period can be as high as 26 weeks "Although there are currently many treatments for rheumatoid arthritis, many patients are not yet able to reach the goal of entering clinical remission or maintaining low disease activity," said Dr Roy M Fleischmann, head of clinical trials at SELECT-COMPARE and clinical professor at the University of Texas Southwestern Medical Center "
about JAK signaling pathways and JAK inhibitors
JAK protein kinase family is made up of THE tyrosine kinase family of JAK1, JAK2, JAK3, TYK2 They play an important role in the signal cascades of a variety of type 1 and type 2 cytokine receptors Because the JAK-mediated cytokine signaling pathway is important in immunodeficiency and tumor diseases, the JAK kinase family has become an important target for the treatment of these diseases the physiological effects and JAK inhibitor information mediated by members of the different JAK families (Photo: Source: Supplied 4) the first generation of JAK inhibitors including tofacitinib, baricitinib, ruxolitinib, and oclacticinib They have an inhibitory effect on multiple JAK family members These inhibitors have shown good efficacy in the treatment of inflammatory and tumor diseases However, because the JAK family mediates the signaling of multiple cytokines, the total suppression of the JAK family can also have a variety of side effects, including infection, anemia, neutropeulocytosis, lymphocytic reduction, and hyperlipidemia therefore, the development of second-generation JAK inhibitors is aimed at increasing the selectivity of inhibitors, while maintaining the unaffected function of other cytokines while inhibiting specific disease-related signaling pathways This has the potential to reduce the side effects of JAK inhibitors Currently, in addition to the approved Inrebic and Rinvoq, the JAK1 selective inhibitor filgotinib, developed jointly by Gilead Sciences and Galapagos, is expected to file a new drug application (NDA) this year to treat rheumatoid arthritis In addition, a number of JAK1, JAK3, and TYK2-specific inhibitors are in clinical development we expect these JAK-specific inhibitors to improve patients' symptoms while reducing the side effects of therapy and further improving their lives References:® Retrieved August 16, 2019, from https:// 2, AbbVie Receives FDA Approval of RINVOQ ™ (upadacitin), an JAK For The End of The Moderate to Rheumatoid Arthritis Retrieved August 16, 2019, from https:// 3 s O'Shea and Gadina, (2019) Selective Janus kinase pondes come of age Nature Reviews Rheumatology, https://doi.org/10.1038/s41584-018-0155-9 Schwartz et al., (2017) JAK inhibition as a dyweud for the fod immune and the rhydiseases Nature Reviews Drug Discovery https://doi.org/10.1038/nrd.2017.201 Harrison et al., (2017) Janus kinase-2 fedratinib in patients with myelofibrosis previously ly lyth lyth lyd with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multi-study The Lancet Haematology DOI: https://doi.org/10.1016/S2352-3026 (17) 30088-1