Change abnormal gene expression, bet inhibitor, phase 2 clinical positive

Today, constellation pharmaceuticals announced that its selective bet inhibitor cpi-0610 showed good clinical activity in a phase 2 clinical trial called manifest to treat patients with myelofibrosis This trial is mainly aimed at patients who have not received JAK inhibitor treatment and patients who have developed resistance or intolerance to ruxolitinib, a marketed therapy Bone marrow fibrosis is a rare and serious bone marrow disease, which disturbs the normal process of blood cell formation The patient's bone marrow will gradually be replaced by fibrotic scar tissue, thus limiting the ability of bone marrow to generate blood cells The production of blood cells transfers from bone marrow to spleen and liver, causing organ enlargement Patients will also have extreme fatigue, shortness of breath, subcostal pain, fever, night sweat, pruritus and bone pain and other symptoms When myelofibrosis occurs by itself, it is called primary myelofibrosis Secondary myelofibrosis occurs when excess erythropoiesis (polycythemia vera) or thrombopoiesis (primary thrombocytopenia) evolves into myelofibrosis Currently, the approved therapeutic drugs include Jak1 / JAK2 inhibitor jakafi (ruxolitinib) which was launched in 2011 and JAK2 and FLT3 inhibitor inrebic (fedratinib) which was approved this year Cpi-0610, a drug under research of constellation company, is a selective bet inhibitor It can inhibit the production of proinflammatory cytokines by inhibiting bet and reducing the expression level of abnormal expression genes At present, cpi-0610 is used as single drug therapy or combined with JAK inhibitor in clinical trials to treat patients with myelofibrosis According to constellation, cpi-0610 has the potential to become the best in class bet inhibitor ▲ schematic diagram of working mechanism of cpi-0610 (picture source: reference [2]) In a phase 2 clinical study called manifest, patients with myelofibrosis were divided into three cohorts In the 1 / 2 cohort, patients who had previously developed resistance or intolerance to ruxolitinib received single drug treatment of cpi-0610 or second-line treatment of combination of cpi-0610 and ruxolitinib, respectively As of June 27, 2019, cpi-0610 showed good clinical activity in the treatment of patients with myelofibrosis In cohort 3, patients who had not previously been treated with JAK inhibitors received first-line treatment with a combination of cpi-0610 and ruxolitinib According to the test data, the company will release detailed test data at this year's annual meeting of the American Hematology Society "Cpi-0610 shows good clinical activity in patients who have not been treated with JAK inhibitors and in patients who are resistant or intolerant to ruxolitinib Based on these positive data, we have increased the number of patients in the manifest trial, hoping to see more comprehensive trial data, "said Mr Jigar raythatha, President and CEO of constellation," we expect to start phase 3 clinical trials in 2020, and cpi-0610 will be used as a first-line treatment for patients with myelofibrosis who have not received JAK inhibitor treatment " reference material: [1] Constellation Pharmaceuticals Announces Third-Quarter and Nine-Month 2019 Financial Results, Retrieved November 6, 2019, from https:// [2] Developing Next-Generation Epigenetic Treatments for Cancer Patient, Retrieved November 6, 2019, from http://ir.constellationpharma.com/static-files/45aaf5b4-ddd9-4826-a289-982fb1d74f8e A kind of