Merck Announces Strong Data For Evobrutinib Multiple Sclerosis For 108 Weeks!

- Jun 04, 2020-

Merck KGaA's biopharmaceutical company EMD Serono recently released long-term efficacy and safety data for the oral, highly selective BTK inhibitor evobrutinib in the treatment of adult patients with relapsing multiple sclerosis (RMS). These results are from the Phase II Open Label Extension (OLE) study.


The latest data indicate that evobrutinib is the first BTK inhibitor to report efficacy and safety data for up to 108 weeks in the treatment of MS. evobrutinib is the first and only BTK inhibitor that shows high efficacy for 108 weeks. There is no new safety signal during the 60-week open label extension period (OLE), which is consistent with data from 1,200 patients with MS or other diseases who have been treated with evobrutinib to date.


Luciano Rossetti, global head of R&D at Merck Serono, said: "These data show that evobrutinib has a continuous and highly impact on the annualized recurrence rate within 108 weeks of treatment. The maximum efficacy is clearly related to the BTK footprint, which further validates our The choice of dose for this phase of the program. We are also encouraged by the broad and consistent safety data of evoburtinib, including no increase in serious infections in more than 1,200 patients within 2 years."


The annual relapse rate (ARR) results of the double-blind period of the study remained unchanged during the open-label extension period. Patients who received evobrutinib 75 mg BID (twice a day) during the double-blind period had an ARR of 0.11 (95% CI) at week 48 : 0.04–0.25), the ARR at week 108 is 0.12 (95% CI: 0.06–0.22).


The data from the Phase II study continue to prove that the BID dosing regimen is more effective than the QD (once a day) dosing regimen in clinical outcomes, as evidenced by the reduction in ARR. Modeling data shows that in almost all patients, the bottom BTK occupancy rate must be greater than 95% to achieve the highest efficacy, and the BID dosing regimen can achieve this effect well.


The data previously published in the New England Journal of Medicine (NEJM) reported the results of the phase II study: at week 24, evobrutinib significantly reduced the cumulative number of T1-Gd-enhanced lesions, reaching the main end. At week 48, all patients can enter the open label extension period (OLE) to evaluate the long-term efficacy and safety of evobrutinib.


Dr. Xavier Montalban, Chairman and Director of the Department of Neuroimmunology and the Department of Neurorehabilitation of the Catalonia Multiple Sclerosis Center (Cemcat) at the University Hospital of Valde Hebron in Barcelona, Spain, said: "The efficacy and safety of the 108 weeks of the entire double-blind period and OLE period Sexual data is very strong. These results, combined with high selectivity, indicate that evobrutinib has the potential to provide a very promising treatment for MS."


Of the 267 randomized patients, 213 patients completed 108 weeks of treatment (48 weeks in the main study and 60 weeks in OLE). Evobrutinib is generally well tolerated and maintains consistent safety during OLE, including no increase in infection, and overall no new safety signals have been found. Consistent with the high selectivity of evobrutinib, patients participating in the trial did not experience systemic side effects such as gastrointestinal disorders. In the phase II trial, the most common adverse reactions of any grade associated with evobrutinib included nasopharyngitis and elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipase.


Temporary increase in liver transaminases is limited to the first 24 weeks after initiation of evobrutinib treatment, and was not observed in patients who continued to use evobrutinib treatment during the OLE phase.

evobrutinib

evobrutinib chemical structural formula (Source: medchemexpress.cn)


After reaching the primary endpoint at the 24th week of treatment in the phase II study, evobrutinib entered phase III clinical development. The two new trials EVOLUTION RMS 1 and 2 are multicenter, randomized, parallel group, double-blind, double-simulation, positive drug-controlled trials, conducted in RMS patients, the main end point of each trial is the ARR of patients after 96 weeks of treatment . Secondary endpoints include the appearance of new or enlarged T2 lesions assessed by MRI scans, and progressive disability as measured by the Extended Disability Status Scale (EDSS).


Multiple sclerosis (MS) is a chronic inflammatory central nervous system disease and the most common non-invasive, disabling neurological disease in young people. It is estimated that approximately 2.3 million people worldwide have 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 relapse of multiple sclerosis is the most common.


Evobrutinib (M2951) is currently in clinical development to explore its potential as a treatment for multiple sclerosis (MS). This medicine is an oral, highly selective Bruton tyrosine kinase (BTK) inhibitor. BTK plays an important role in the development and function of various immune cells including B lymphocytes and macrophages.


evobrutinib is designed to inhibit major B cell responses, such as proliferation, antibody and cytokine release, without directly affecting T cells. BTK inhibition is believed to inhibit autoantibody-producing cells. Preclinical studies have shown that BTK inhibition may have therapeutic effects on certain autoimmune diseases. Currently, the global phase III clinical development project is evaluating evobrutinib for MS. The project includes two key phase III studies, EVOLUTION RMS 1 and 2. evobrutinib is currently in clinical development and has not been approved by any country.