Merck's Evobrutinib: First BTK Inhibitor to Significantly Reduce Slowly Expanding Lesions in Relapsing Multiple Sclerosis

October 24, 2021 News /BioonBIOON/ -- Merck KGaA recently announced a Phase 2 at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)Clinical Trialpost hoc analysis data confirm:Oral, CNS-penetrant, fully covalent Bruton's tyrosine kinase inhibitor (BTKi) evobrutinib may affect brain injury associated with chronic inflammation in the central nervous system (CNS)., which makes itThe first BTKi proven to significantly reduce slowly expanding lesions (SEL)。SEL is a chronic, active, demyelinating multiple sclerosis (MS) lesion, considered an early indicator of MS disease progression.

Analysis of the Phase 2 study evaluated the effect of evobrutinib treatment on SEL volume from baseline to Week 48. Compared with placebo,Evobrutinib reduced SEL volume in a dose-dependent manner, with the greatest effect observed at 75 mg twice daily (p=0.047).. In subgroup analysis,The effect of evobrutinib on SEL volume is also particularly pronounced in patients with more severe disease.。

SEL is a potential consequence of cumulative neuronal injury, particularly axonal loss, and its occurrence is independent of the acute inflammation associated with Gd+ lesions. These results, together with the previously reported reduction in Gd+ lesions, suggest...Evobrutinib reduces acute and chronic neuroinflammation, both of which jointly contribute to disability progression.。This analysisFirst Evidence Shows BTK Inhibitors Significantly Reduce SEL Volume in Patients with Relapsing MS, providing further evidence supporting the mechanism of action of evobrutinib in the treatment of RMS, and highlighting the potential impact of this molecule on neurodegeneration and disease progression.

In addition to SEL volume measurement, evaluateBlood neurofilament light chain (NfL) levels are another emerging method for assessing multiple sclerosis (MS) disease progression.. Previously shared data showed,As early as Week 12, evobrutinib significantly reduced blood NfL levels, and at the final analysis time point of Week 24, NfL levels continued to decrease.

Additional new data from a post hoc analysis of a Phase 2 trial presented at the meeting indicated that high baseline NfL levels predict an increased risk of relapse and MRI lesion activity. During the 24-week treatment period, evobrutinib 75 mg once daily or twice daily improved MRI and relapse outcomes compared with placebo or evobrutinib 25 mg once daily, even in patients with advanced MS who had higher baseline NfL levels.These preliminary findings from NfL and SEL data continue to demonstrate the potential benefit of evobrutinib in disease progression.

The conference also announced BTK inhibitors in`Autoimmunity`the most comprehensive safety dataset in the disease. This analysis utilized data from three Phase 2Clinical Trial1,083 Cases of SystemicLupus Erythematosus(SLE), classRheumatic arthritis(RA) Pooled data from RMS patients, including various doses (25 mg or 75 mg once daily, or 50 mg or 75 mg twice daily). Analysis showed that evobrutinib was generally well-tolerated, with the incidence of adverse events similar to placebo across indications and trials. The most commonly reported adverse events were urinary tract infection (9.5% vs 8.5% [placebo]), nasopharyngitis (7.3% vs 5.5% [placebo]), diarrhea (6.2% vs 4.8% [placebo]), and elevated alanine aminotransferase (ALT) (2.9% vs 1.5% [placebo]). Hepatic transaminase elevations were asymptomatic and reversible upon discontinuation.

Dr. Danny Bar Zohar, Head of Global Development, Healthcare Business at Merck, stated: “There is an urgent need for new therapies targeting early chronic neuroinflammation in RMS to effectively prevent the progression and accumulation of disability. The first-in-class BTKi data for evobrutinib regarding SEL and NfL, which are considered predictive of disease progression, further reinforces our belief in the potential of evobrutinib as an optimal treatment option for patients with relapsing MS.”

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and the most common non-traumatic, disabling neurological disease among young adults. It is estimated that approximately 2.8 million people worldwide are affected by MS. Although symptoms may vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs, and problems with muscle strength and coordination. The relapsing form of multiple sclerosis is the most common.

Evobrutinib (M2951) is currently under clinical development to evaluate its potential as a treatment for MS. The drug is an oral, highly selective Bruton's tyrosine kinase (BTK) inhibitor. BTK plays a critical role in the development and function of various immune cells, including B lymphocytes and macrophages.

Evobrutinib is designed to inhibit key B-cell responses, such as proliferation and the release of antibodies and cytokines, without directly affecting T cells.BTK inhibition is believed to suppress autoantibody-producing cells, and preclinical studies indicate that BTK inhibition may potentially benefit certainAutoimmunityhas therapeutic effects on the disease. Currently, a global Phase III clinical development program is evaluating evobrutinib for the treatment of MS, which includes two pivotal Phase III studies, EVOLUTION RMS 1 and 2. evobrutinib is currently under clinical development and has not yet been approved in any country. (Bioon.com)

Original Source:New Data Presented at ECTRIMS Show Evobrutinib is First BTK Inhibitor to Demonstrate a Significant Reduction in Slowly Expanding Lesions (SEL) in Patients with RMS