New-base JAK2 inhibitor fedratinib shows strong efficacy in refractopathic patients

The updated analysis showed that fedratinib therapy showed a clinically significant response rate in patients with bone marrow fibrosis who had previously been treated with ruxolitinibThis latest analysis of fedratinib uses the principle of intent therapy (ITT) and provides a narrower definition of ruxolitinib relapse, incurable or intolerant patientsIn the ITT group (n-97), at the end of the 6th week of treatment, the proportion of patients with spleen volume reduced by 35% was 31% (95% CI:22,41)Of these 97 patients, 79 (81%) met the narrower standard of ruxolitinib resistance or intoleranceIn this queue, the proportion of patients with reduced spleen volume by 35% at the end of the first 6 weeks was 30% (95% CI:21,42), consistent with the response rate observed in the ITT populationIn addition, in the ITT group (95% CI:18,37) and included in the narrow standard analysis (95% CI: 17, 39), the rate of symptom asymptomatic remission was 27% of patientsIn terms of safety, the most common level 3-4 hematological abnormalities were anemia (46%) and platelet reduction (24%)Among all patients treated, the most common non-hemotherapy adverse events (TEAE) were diarrhea (62%), nausea (56%), vomiting (41%) and constipation (21%)Dr Claire NHarrison, Deputy Director of Oncology and Hematology at NHS Foundation Trust Hospital in London, said: "Bone marrow fibrosis is a serious and rare bone marrow disease and there is currently only one approved treatment, ruxolitinib, and patients may become intolerant or resistant to the treatmentThese updated results show edprungling and symptoms significantly decreased in these difficult patients and increased the potential of fedratinib in patients who no longer benefited from ruxolitinib treatmentDr Alise Reicin, President of Global Clinical Development at New Base, said: "Fedratinib is likely to become the first new treatment for patients with bone marrow fibrosis since 2011Myelofisis patients' relapse, incurability or intolerance to ruxolitinib represents a highly unmet medical need, and we are committed to bringing this important treatment to this groupfedratinib molecular structure (Photo: Wikipedia) fedratinib is an oral kinase inhibitor that is active in wild and mutantly-activated Janus-related kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3)The drug is a JAK2 selective inhibitor that has a higher inhibitory effect on JAK2 than family members JAK1, JAK3 and TYK2Abnormal activation of JAK2 is associated with bone marrow hyperplasia (MPN), including bone marrow fibrosis and true red blood cell hyperplasiaIn cell models that express mutation-activated JAK2 or FLT3, fedratinib reduces the phosphorylation of signal transductors and transcriptionactivator (STAT3/5) proteins, inhibits cell proliferation, and induces apoptosis cell death In the JAK2V617F-driven mouse model of bone marrow hyperplasia, fedratinib blocked STAT3/5 phosphorylation, improved survival, and improved disease-related symptoms, including white blood cell reduction, red blood cell ratio, spleen enlargement, and fibrosis , the new drug application for fedratinib for bone marrow fibrosis (NDA) is currently under fda review and will be reviewed on September 3, 2019 Previously, the FDA had granted fedratinib the right to treat orphan drugs for secondary and primary bone marrow fibrosis The new base also plans to evaluate the combination therapy of fedratinib with another drug, luspatercept Bone marrow fibrosis is a serious bone marrow disease that destroys the body's normal blood cell production original origin: Celgene UpdateD Analysis of Jakarta2 Fedratinib Show Clinical Clinically Meaningful Responses in PatientsLy Treated for Myelofibrosis with Ruxolitinib