Express significantly reduces inflammation indicators in patients with multiple sclerosis, and the phase 2 clinical results of brain-permeable BTK inhibitors are positive

▎Editor of WuXi AppTec content team Recently, Merck KGaA of Germany announced the post-mortem analysis data of a phase 2 clinical trial of the brain-permeable BTK inhibitor evobrutinib for the treatment of patients with multiple sclerosis (MS)
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Test results show that evobrutinib can improve brain damage related to chronic inflammation of the central nervous system (CNS)
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The press release states that evobrutinib is the first BTK inhibitor to significantly reduce slow expanding lesions (SEL)
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SELs are early indicators of the progression of chronic, active, and demyelinating multiple sclerosis
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Multiple sclerosis is an autoimmune disease that occurs in the central nervous system and is caused by the autoimmune system attacking the myelin sheath
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Myelin sheath is a lipid that wraps and protects nerve fibers in the brain and spinal cord
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Inflammation and tissue damage caused by disease can disrupt the normal function of the brain, optic nerve, and spinal cord
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The main age of onset is 20 to 40 years old, which is the second only cause of disability in young and middle-aged people after trauma
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Approximately 2.
5 million people are affected worldwide
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There is currently no curative treatment
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Evobrutinib is a highly selective oral inhibitor of BTK that can cross the blood-brain barrier
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BTK is important for the development and function of various immune cells including B lymphocytes and macrophages
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Therefore, inhibition of BTK is expected to inhibit cells that produce autoantibodies
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Preclinical studies have shown that inhibition of BTK may have a therapeutic effect on certain autoimmune diseases
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Evobrutinib is designed to inhibit the proliferation of B cells and release antibodies/cytokines without directly affecting T cell functions
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▲The molecular structure of Evobrutinib (picture source: PubChem) This post-mortem analysis evaluated the effect of evobrutinib treatment on patients' SEL volume for 48 weeks
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The results of the trial showed that compared with placebo, evobrutinib reduced the volume of SEL in a dose-dependent manner, and the effect of 75 mg twice a day was the best (p=0.
047)
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In addition, in a subgroup analysis, the effect of evobrutinib on SEL volume was particularly significant in patients with more advanced disease
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SEL is a potential result of cumulative neuronal damage (especially loss of axons)
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Previously published results showed that evobrutinib can also significantly reduce Gd+ lesions associated with acute inflammation
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This indicates that evobrutinib can improve the acute and chronic neuroinflammation that together cause the patient’s symptoms to worsen
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In addition, the blood neurofilament light chain (NfL) level associated with disease progression in the evobrutinib group decreased significantly as early as the 12th week, and the level still decreased at the final analysis time point of the 24th week
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The comprehensive safety analysis summarized the data of 3 phase 2 clinical trials of evobrutinib in patients with systemic lupus erythematosus, rheumatoid arthritis and relapsing multiple sclerosis, including 1083 patients
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Evobrutinib is generally well tolerated, and the incidence of adverse events is similar to that of the placebo group
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The principal investigator of this clinical trial, Dr.
Xavier Montalban of Vall d'Hebron University in Spain, said: “This analysis shows for the first time that BTK inhibitors can significantly reduce the SEL volume of patients with relapsing multiple sclerosis.
The mechanism of action provides further evidence and emphasizes the potential impact of this molecule on neurodegeneration and disease progression
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"Reference: [1] 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.
Retrieved October 15, 2021, from https:// -Inhibitor-to-Demonstrate-a-Significant-Reduction-in-Slowly-Expanding-Lesions-SEL-in-Patients-with-RMS Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
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