evobrutinib (M2951) / EMD Serono 
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 5 Diseases   3 Trials   3 Trials   423 News 


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  • ||||||||||  tolebrutinib (SAR442168) / Sanofi
    Comparative CNS Pharmacology of Tolebrutinib Versus Other BTK Inhibitor Candidates for Treating MS (Virtual Poster Hall) -  Feb 20, 2022 - Abstract #ACTRIMSForum2022ACTRIMS_Forum_540;    
    1) The cellular target must be expressed in CNS-resident cells, 2) those cells must be involved in the pathophysiology, 3) the drug must cross the blood brain barrier to engage the target, and 4) inhibiting the target leads to a pharmacological benefit. We conclude that tolebrutinib is the only late-stage candidate that meets each of the first three criteria.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Evobrutinib enhances remyelination (Virtual Poster Hall) -  Feb 20, 2022 - Abstract #ACTRIMSForum2022ACTRIMS_Forum_490;    
    We conclude that tolebrutinib is the only late-stage candidate that meets each of the first three criteria. Our data are pointing microglia as a new target to favor remyelination and highlight Evobrutinib as a potent candidate enhancing remyelination.
  • ||||||||||  evobrutinib (M2951) / EMD Serono, tolebrutinib (SAR442168) / Sanofi
    Investigating Bruton Tyrosine Kinase Inhibition in human and mouse myeloid cells to further elucidate cell-specific and disease-relevant mechanisms in multiple sclerosis (Virtual Poster Hall) -  Feb 20, 2022 - Abstract #ACTRIMSForum2022ACTRIMS_Forum_475;    
    The lack of a measurable effect in mouse-derived macrophages is suggestive of a possible species difference in the cellular role of BTKs in the context of inflammation. Furthermore, due to the comparable mRNA transcript levels of btk between RRMS and controls, this finding suggests that the pathophysiological relevance/rational of targeting BTK in MS is not due to an overall increase in gene expression within the CD14+ monocytes, but perhaps rather due to either translational and/or post-translational modifications.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Clinical, Journal:  Evobrutinib, a covalent Bruton's tyrosine kinase inhibitor: Mass balance, elimination route, and metabolism in healthy participants. (Pubmed Central) -  Feb 10, 2022   
    P1
    Only one major metabolite M463-2 (MSC2430422) was identified in plasma above the 10% of total drug exposure threshold, which classifies M463-2 (MSC2430422) as a major metabolite according to the US Food and Drug Administration (FDA; metabolites in safety testing [MIST]) and the European Medicines Agency (EMA; International Conference on Harmonization [ICH] M3). These results support further development of evobrutinib and may help inform subsequent investigations.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment open:  MS200527_0078: Drug-Drug Interaction Study of Evobrutinib and Transporter Substrates (clinicaltrials.gov) -  Nov 18, 2021   
    P1,  N=40, Recruiting, 
    The EAIR of TEAEs (events/100 pt-years) for evobrutinib vs placebo were similar by indication: MS: 119.7 vs 148.3; RA: 331.8 vs 306.8; SLE: 342.9 vs 302.1. Not yet recruiting --> Recruiting
  • ||||||||||  Review, Journal:  Targeting B Cells to Modify MS, NMOSD, and MOGAD: Part 1. (Pubmed Central) -  Oct 14, 2021   
    To understand the significance of this breakthrough in the context of the current MS therapeutic armamentarium, this review more closely examines the clinical development of CD20 depletion and the pioneering contribution of rituximab. Phase 3 and the recently published postmarketing studies will be highlighted to better understand the relevant efficacy data and safety aspects of long-term B-cell depletion.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment closed:  EVOLUTION RMS1: Study of Evobrutinib in Participants With RMS (evolutionRMS 1) (clinicaltrials.gov) -  Oct 4, 2021   
    P3,  N=930, Active, not recruiting, 
    Role of the Study Sponsor: This study was sponsored by EMD Serono Research and Development Institute, Inc., an affiliate of Merck KGaA, Darmstadt, Germany. Recruiting --> Active, not recruiting
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment closed:  Study of Evobrutinib in Participants With RMS (evolutionRMS 2) (clinicaltrials.gov) -  Oct 4, 2021   
    P3,  N=930, Active, not recruiting, 
    Recruiting --> Active, not recruiting Recruiting --> Active, not recruiting
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Journal:  Imaging meningeal inflammation in CNS autoimmunity identifies a therapeutic role for BTK inhibition. (Pubmed Central) -  Sep 25, 2021   
    We randomized mice with evidence of meningeal contrast enhancement on MRI scans performed at 6 weeks post-immunization, to treatment with either vehicle or evobrutinib [a Bruton tyrosine kinase (BTK) inhibitor] for a period of 4 weeks...We used ultra-high field MRI to identify areas of meningeal inflammation and to track them over time in SJL/J mice with experimental autoimmune encephalomyelitis, and then used this model to identify BTK inhibition as a novel therapeutic approach to target meningeal inflammation. The results of this study provide support for future studies in multiple sclerosis patients with imaging evidence of meningeal inflammation.
  • ||||||||||  tamoxifen / Generic mfg.
    [VIRTUAL] The role of human and mouse BTK in myeloid cells (ePoster Library) -  Sep 23, 2021 - Abstract #ECTRIMS2021ECTRIMS_2226;    
    Animals treated with evobrutinib showed significant clinical amelioration...We inactivated BTK using mice carrying a floxable BTK allele that were crossed with mice carrying the Tamoxifen (Tam)-inducible Cre recombinase under Cx3CR1 promoter... Overall, these experiments demonstrate that human and mouse myeloid cells may represent a cellular target of the action of BTK inhibitors and that BTK in long-lived myeloid cells does support the expression of neuroinflammation.
  • ||||||||||  evobrutinib (M2951) / EMD Serono, tolebrutinib (SAR442168) / Sanofi, rilzabrutinib (SAR444671) / Sanofi
    Review, Journal:  Recent Advances in BTK Inhibitors for the Treatment of Inflammatory and Autoimmune Diseases. (Pubmed Central) -  Sep 19, 2021   
    Rilzabrutinib, a covalent reversible BTK inhibitor, is now in phase 3 clinical trials and also offers a promising future. An analysis of the protein-inhibitor interactions based on published co-crystal structures provides useful clues for the rational design of safe and effective small-molecule BTK inhibitors.
  • ||||||||||  Review, Journal:  Bruton's Tyrosine Kinase Inhibition for the Treatment of Rheumatoid Arthritis. (Pubmed Central) -  Sep 7, 2021   
    While the results of BTK inhibitors in RA animal models have been promising, the ensuing human clinical trial outcomes have been rather equivocal. This review will outline the mechanisms of BTK inhibition and its potential impact on immune mediated disease, the types of BTK inhibitors being studied for RA, the findings from both preclinical and clinical trials of BTK inhibitors in RA, and directions for future research.
  • ||||||||||  tamoxifen / Generic mfg.
    [VIRTUAL] The role of human and mouse BTK in myeloid cells (ePoster Library) -  Aug 3, 2021 - Abstract #ECTRIMS2021ECTRIMS_880;    
    Animals treated with evobrutinib showed significant clinical amelioration...We inactivated BTK using mice carrying a floxable BTK allele that were crossed with mice carrying the Tamoxifen (Tam)-inducible Cre recombinase under Cx3CR1 promoter... Overall, these experiments demonstrate that human and mouse myeloid cells may represent a cellular target of the action of BTK inhibitors and that BTK in long-lived myeloid cells does support the expression of neuroinflammation.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Trial completion:  MS200527_0059: Effect of Hepatic Impairment on M2951 (BTK Inhibitor) PK (clinicaltrials.gov) -  Jul 12, 2021   
    P1,  N=24, Completed, 
    Overall, these experiments demonstrate that human and mouse myeloid cells may represent a cellular target of the action of BTK inhibitors and that BTK in long-lived myeloid cells does support the expression of neuroinflammation. Active, not recruiting --> Completed
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment closed:  MS200527_0059: Effect of Hepatic Impairment on M2951 (BTK Inhibitor) PK (clinicaltrials.gov) -  Jun 23, 2021   
    P1,  N=24, Active, not recruiting, 
    Results further show that ibrutinib and zanubrutinib could exploit different mechanisms at the viral entry and replication stage and could be repurposed as potential inhibitors of SARS-CoV-2 pathogenesis. Recruiting --> Active, not recruiting
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    [VIRTUAL] Determination of a clinically effective evobrutinib dose: exposure-response analyses of a phase II MS study (Room Helsinki) -  May 30, 2021 - Abstract #EAN2021EAN_1056;    
    P2
    In conjunction with a recent phase II trial reporting that evobrutinib is safe and effective in MS, our mechanistic data highlight therapeutic BTK inhibition as a landmark towards selectively interfering with MS-driving B-cell properties. An evobrutinib dose of 45mg BID with food will be pharmacologically effective and is appropriate for clinical use in phase III multiple sclerosis trials.