PI3K inhibitor umbralisib-CD20 inhibitor ublituximab for CLL trial was discontinued early due to significant efficacy

Chronic lymphocytic leukemia (chronic lymphocytic leukemia, CLL), chronic lymphocytic leukemia (chronic lymphocytic leukemia, CLL), an elderly disease characterized by the cloned proliferation of highly differentiated lymphocytes with insufficiency of immune functionCLL cells invade lymph nodes, spleen, bone marrow hyperplasia is significantly active, mainly small lymphocytes, accounting for 50%-90%, the number of peripheral blood lymphocytes significantly increased, and has a more mature lymphocyte surface markersThere are expected to be more than 20,000 newly diagnosed CLL cases in the United States by 2020Although The symptoms of CLL may disappear for some time after initial treatment, the disease is considered incurable and many people will need additional treatment due to the recurrence of malignant cellsinnovative oral PI3K inhibitor umbralisib joint CD20 antibody ublituximab (U2), reached the main end of the study of progression-free survival (PFS) in the mid-stage analysis of UNITY-CLL in a phase 3 clinical trial for patients with recurrent/refractive chronic lymphocytic leukemia (CLL)After review by the Independent Data Security Monitoring Board (DSMB), it is recommended that the trial be concluded prematurelyThe company is expected to file a regulatory application by the end of the yearThe umbralisib, developed by TG Therapeutics, is a new generation of PI3K inhibitorsIt is more specific to PI3K , than other PI3K inhibitors , and does not inhibit PI3And it can increase drug tolerance by inhibiting a protein called CK1-th, preventing disruption of the function of regulatory T cellsIt has been identified by the FDA as a breakthrough therapy for the treatment of patients with lymphoma in the limbic areaumbralisib is a bi-effect inhibitor of phosphoric inositol-3-kinase (PI3K) and casein kinase 1(CK-1) ,, which may enable it to overcome some of the tolerable problems associated with the first generation of PI3K inhibitorsPhosphatidylinol-3 kinase (PI3K) is a class of enzymes involved in cell proliferation and survival, cell differentiation, intracellular transport and immune functionPI3K has four subtypes (alpha, beta, gamma, and gamma), in which the gamma subtype is strongly expressed in cells of hematopoietic origin and is often associated with B-cell-related lymphomaumbrasib hasnano-
molar effect on PI3K subtypes and is highly selective to alpha, beta, and gamma subtypesUmbralisib also uniquely inhibits casein kinase 1-1 (CK1-s), which may have a direct anti-cancer effect, or may regulate the T-cell activity previously observed in PI3K inhibitors associated with immunomediated adverse eventsublituximab is a new type of glycogen engineering anti-CD20 monoclonal antibody that targets the specific epimostes of CD20 antigens on mature B lymphocytesCurrently, the drug is being clinically developed in Phase III for the treatment of multiple sclerosis (MS) and chronic lymphocytic leukemia (CLL)ublituximab is a new type of glycosis anti-CD20 monoclonal antibody that targets the unique table of CD20 antigens on mature B lymphocytes, which is different from the many CD20 monogenics currently available, including of of atumumumab, ocrelib/rituximab, obinutuzumab (GA101)the company has published positive top-line results from the Global Phase III UNITY-CLL testThe trial was conducted in patients with previously untreated (initial) and recurrent/refractive (curable) chronic lymphocytic leukemia (CLL) and evaluated the efficacy and safety of the combination drug regimen of umbralisib and ublituximab (U2) and compared it with the obionutuzumab-benzodiazepine nitrogen mustard programmethe trial under a Special Program Assessment (SPA) agreement with the FDAThe results showed that the trial had reached the primary endpoint in the pre-designated mid-stage analysis: according to the independent review board (IRC), the U2 treatment group achieved a statistically significant improvement in progression survival (PFS) compared to the patients with previous lying (initial) and recurrent/difficult(cured) CLL patientsthe trial will be terminated early due to excellent efficacy, as recommended by the Independent Data Safety Monitoring Board (DSMB)Based on the trial's data, TG plans to submit a regulatory application by the end of 2020 for the U2 program to treat patients with previously untreated (initial treatment) and recurrent/refractive (curable) CLL patientsJohn Gribben, MDM, Professor of Medical Oncology at the Barts Cancer Institute in London, Ublituximab combined with unique tables on CD20 molecules, professor of medical oncology at the Barts Cancer Institute in London, UK, said: "We are very pleased to see that this important trial has resulted in positive results in the combination of umbraisib and uitbluximab in front line and in patients with recurrent/refractive CLLToday's results mark the first successful Phase III clinical trial based on PI3K treatment options in the CLL patient population, including patients who have not previously been treatedAt present, CLL is still incurable and there is still an urgent need for new treatment options, especially those that offer different mechanisms and safety treatments"
" the positive results of this trial provide the foundation for this combination therapy to become a new treatment for patients with CLL patients without chemotherapy," said Michael S Weiss, Executive Chairman and CEO of TG Therapeutics We are very grateful to the patients involved in this trial, their families, and the doctors and research team We look forward to submitting these data to the FDA and presenting the full results at a medical conference by the end of 2020 "
currently approved PI3K inhibitors are associated with autoimmune-mediated toxicity, such as hepatotoxicity, pulmonary toxicity, and colitis Compared to approved PI3K inhibitors, umbralisib's specific differences, its unique inhibitory effect on CK1-bar, and its unique and patented chemical structure may have differentiated characteristics in the PI3K inhibitor class previously, the FDA has granted umbralisib four orphan drug (ODD) eligibility, including FL and all 3 MZL (lymph nodes, spleen mZL) In addition, the FDA has granted the breakthrough drug qualification (BTD) for umbralisib treatment in adult patients who have previously received at least one anti-CD20 therapy for recurrent or refractive MZL References: Retrieved 2020-05-05, from the phase 2 phase 2 multimulticenter research of ublituximab, a novel glycogyd anti-CD20 monoclonal antibody, in patients laps reing forms of multi-lago Retrieved 2020-05-05, from MedSci Source: MedSci Original