Beyond the cancer category! First oral BTK inhibitor to enter neuroscience: Merck announces strong data for 108 weeks of evobrutinib multiple sclerosis!

May 25
, 2020 /
bioON/BIOON/ -- EmD Serono, a biopharmaceutical company owned by German pharmaceutical giant Merck KGaA, recently released long-term efficacy and safety data for the treatment of adult patients with recurrent multiple sclerosis (RMS) by oral, highly selective BTK-drug inhibitor evobrutinibThese results are derived from the Phase II Open Label Extension (OLE) studylatest data show that evobrutinib is the first BTK inhibitor to report up to 108 weeks of efficacy and safety data on the treatment of MSevobrutinib is the first and only BTK inhibitor to show a high efficacy of 108 weeksthere are no new safety signals in the 60-week open label expansion period (OLE), which is consistent with the data on 1,200 cases of MS or other diseases treated so far"These data show that evobrutinib has a sustained and high impact on annualized recurrence rates within 108 weeks of treatment," said Luciano Rossetti, head of global research and development atMerck SheranoThe maximum efficacy was significantly related to BTK occupancy, further validating our choice of phase III project doseWe are also encouraged by the broad consistent safety data for evoburtinib, including no increase in severe infections in more than 1,200 patients over 2 years"
the annual recurrence rate (ARR) results of the study remained unchanged during the open label expansion period, with patients receiving evobrutinib 75mg BID (2 times per day) during the double-blind period at 0.11 (95% CI: 0.04-0.25) and 0.12 (95%CIRS) in week 108Data from thePhase II study continue to show that BID administration programmes are more effective for clinical outcomes than QD (once a day) delivery programmes, as evidenced by the reduction of ARRModeling data show that the trough BTK occupancy rate in almost all patients must be greater than 95% to achieve the highest efficacy, and BID administration can achieve this effect wellpreviously published data in the New England Journal of Medicine (NEJM) reported the results of the Phase II study: In week 24, evobrutinib significantly reduced the cumulative amount of T1-Gd-enhanced lesions to the primary endpoint than placebo At week 48, all patients can enter the Open Label Extension (OLE) period to assess the long-term efficacy and safety of evobrutinib "The 108-week efficacy and safety data for the entire double-blind and OLE period are very strong," said Dr Xavier Montalban, chair and director of the Department of Neuro
immunology and Neurorehabilitation at the University Hospital of Valdhebrun, Barcelona, Spain, These results, combined with high lysivity, suggest that evobrutinib has the potential to provide a very promising treatment for MS treatment "
of 267 randomized patients, 213 completed 108 weeks of treatment (48 weeks in the main study and 60 weeks of OLE) evobrutinib is generally well tolerated and maintains consistent safety during OLE, including no increase in infections, and no new safety signals are found in general Consistent with the high selectivity of evobrutinib, patients who participated in the trial did not show systemic side effects such as gastrointestinal disorders In Phase II trials, the most common adverse reactions associated with evobrutinib include elevated levels of nasopharyngitis and alanine amino transferase (ALT), temporyininaminotometoase (AST), and lipase temporary increase in liver transaminase was limited to the first 24 weeks after the initiation of evobrutinib therapy, and was not observed in patients who continued to use evobrutinib during OLE period evobrutinib chemical structure (photo source: medchemexpress.cn) entered Phase III clinical development after reaching the main endpoint in the 24th week of treatment in the Phase II study Two new trials, EVOLUTION RMS 1 and 2, are multicenter, randomized, parallel, double-blind, double-simulated, positive drug control trials conducted in RMS patients, with the main endpoint of each trial being ARR after 96 weeks of treatment Secondary endpoints include the emergence of new or expanded T2 lesions assessed by MRI scans, and the ongoing disability measured by extended disability scale (EDSS) multiple sclerosis (MS) is a chronic inflammatory central nervous system disease, the most common non-traumatic, disabling neurological disease in young people It is estimated that about 2.3 million people worldwide suffer from multiple sclerosis Although symptoms may vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs, and strength and coordination problems The type of recurrence of multiple sclerosis is the most common evobrutinib (M2951) is currently under clinical development to explore its potential as a treatment for multiple sclerosis (MS) The drug is an oral, highly selective Bruton tyrosine kinase (BTK) inhibitor BTK plays an important role in the development and function of a variety of immune cells, including B lymphocytes and macrophages evobrutinib is designed to inhibit the release of major B-cell reactions, such as proliferation, antibodies and cytokines, without directly affecting T-cells BTK inhibition is thought to inhibit autoantibodies to produce cells, and preclinical studies have shown that BTK inhibition may have therapeutic effects on some autoimmune diseases Currently, the Global Phase III Clinical Development Project is evaluating the evobrutinib treatment of MS, which includes two key Phase III studies, EVOLUTION RMS 1 and 2 Evobrutinib is currently under clinical development and has not yet been approved by any country (BioValleyBioon.com) original source: New Late-Breaking Data at EAN Indicate Evobrutinib is the First BTK to Report Note, And Safety in MS Over 108 Weeks