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


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  • ||||||||||  remibrutinib (LOU064) / Novartis
    Remibrutinib exhibits improved target selectivity and potency in vitro () -  Nov 20, 2022 - Abstract #AECF2022AECF_106;    
    The same pattern was confirmed in a quantitative assessment of binding constants to a subset of kinases.CONCLUSIONS BTKi currently in clinical development for MS exhibit a varying degree of selectivity across the human kinome with the highest selectivity seen for remibrutinib. Such a distinction may translate into differences in safety and clinical efficacy.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Evobrutinib acts on microglia: therapeutic implication in progression of MS? () -  Nov 20, 2022 - Abstract #AECF2022AECF_54;    
    Conclusion We showed that BTK inhibition by evobrutinib can shape microglial cells in an anti-inflammatory manner, diminishing inflammatory responses of microglial cells. These data highlight the therapeutic potential of the BTK inhibitor evobrutinib in ameliorating pro-inflammatory activity of microglia, an assumed key process in chronic progression of MS.
  • ||||||||||  evobrutinib (M2951) / EMD Serono, tolebrutinib (SAR442168) / Sanofi
    Review, Journal:  Bruton's Tyrosine Kinase Inhibition in Multiple Sclerosis. (Pubmed Central) -  Nov 8, 2022   
    Inhibition of BTK has emerged as an attractive strategy to target cells of the adaptive and innate immune system outside and within the CNS. BTKIs carry great therapeutic potential across the MS spectrum, where key pathobiology aspects seem confined to the CNS compartment.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment closed:  EVOLUTION RMS1: Study of Evobrutinib in Participants With RMS (evolutionRMS 1) (clinicaltrials.gov) -  Nov 8, 2022   
    P3,  N=898, Active, not recruiting, 
    BTKIs carry great therapeutic potential across the MS spectrum, where key pathobiology aspects seem confined to the CNS compartment. Recruiting --> Active, not recruiting
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment closed:  Study of Evobrutinib in Participants With RMS (evolutionRMS 2) (clinicaltrials.gov) -  Nov 8, 2022   
    P3,  N=898, Active, not recruiting, 
    Recruiting --> Active, not recruiting Recruiting --> Active, not recruiting
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    B cells infiltrating the MS brain: from local maturation to targeting by evobrutinib​​​​ (ePoster Area) -  Oct 18, 2022 - Abstract #ECTRIMS2022ECTRIMS_1560;    
    no difference in btk mRNA expression between RRMS and control suggests the effect of BTKis is not transcription associated, but rather due to its direct anti-enzymatic activity. Our work reveals that CXCR3+ B cells preferentially mature into ASCs after entering the CNS and that the development of this pathogenic subset is a promising target of next-generation BTK inhibitor evobrutinib in both the periphery and CNS in MS.
  • ||||||||||  Journal:  Bruton's Tyrosine Kinase Inhibitors in Multiple Sclerosis: Pioneering the Path Towards Treatment of Progression? (Pubmed Central) -  Oct 13, 2022   
    In this review, we discuss where and to what extent BTK is involved in the immunological and molecular cascades driving MS progression. We furthermore summarize all mechanistic, preclinical, and clinical data on the various BTK inhibitors (evobrutinib, tolebrutinib, fenebrutinib, remibrutinib, orelabrutinib, BIIB091) that are currently in development for treatment of MS, with a particular focus on the potential ability of either drug to control MS progression.
  • ||||||||||  evobrutinib (M2951) / EMD Serono, tolebrutinib (SAR442168) / Sanofi
    Direct comparison of multiple sclerosis drugs in the modulation of inflammatory pathways in microglia (SDCC Halls B-H) -  Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_11155;    
    In the present study, we directly compare the ability of different classes of MS drugs and their active metabolites, Fingolimod (FTY720), Fingolimod Phosphate (pFTY720), Dimethyl Fumarate (DMF), Monomethyl Fumarate (MMF), Teriflunomide (TFD), Evobrutinib (EVO) and Tolebrutinib (TOL) to modulate inflammatory phenotypes in microglia...Additionally, levels of total and phosphorylated NFkB are measured in treated microglia by Homogeneous Time Resolved Fluorescence. Comparative data for the different drug classes are presented and the impact on NFkB signalling is discussed.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    PK/PD data, Journal:  Population pharmacokinetic and pharmacodynamic modeling of evobrutinib in healthy adult participants. (Pubmed Central) -  Sep 29, 2022   
    The simulated percentage of participants with minimum BTKO increased in a dose-dependent manner across the BTKO thresholds of interest (70%, 80%, 90%, and 95% occupancy). Evobrutinib doses of 25 mg once-daily, 50 mg twice-daily, or 75 mg twice-daily while fasted are possible choices for further development, assuming BTKO ≥70% at trough is needed to achieve efficacy.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Journal:  Human T-bet+ B cell development is associated with BTK activity and suppressed by evobrutinib. (Pubmed Central) -  Aug 25, 2022   
    Furthermore, evobrutinib interfered with in vitro class switching, as well as memory recall responses, and disturbed CXCL10-mediated migration of CXCR3+ switched B cells through human brain endothelial monolayers. These findings demonstrate a functional link between BTK activity and disease-relevant B cells and offer valuable insights into how next-generation BTK inhibitors could modulate the clinical course of patients with MS.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Trial completion:  MS200527_0108: DDI Study of Evobrutinib and Carbamazepine (clinicaltrials.gov) -  Aug 22, 2022   
    P1,  N=14, Completed, 
    These findings demonstrate a functional link between BTK activity and disease-relevant B cells and offer valuable insights into how next-generation BTK inhibitors could modulate the clinical course of patients with MS. Recruiting --> Completed
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment open:  EVOLUTION RMS1: Study of Evobrutinib in Participants With RMS (evolutionRMS 1) (clinicaltrials.gov) -  Jul 1, 2022   
    P3,  N=898, Recruiting, 
    The sequential combination of BTK inhibition with B cell depletion allowed the repopulation of B cells, while controlling their pro-inflammatory differentiation and activation. Active, not recruiting --> Recruiting
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment open:  Study of Evobrutinib in Participants With RMS (evolutionRMS 2) (clinicaltrials.gov) -  Jul 1, 2022   
    P3,  N=898, Recruiting, 
    Active, not recruiting --> Recruiting Active, not recruiting --> Recruiting
  • ||||||||||  Kesimpta (ofatumumab subcutaneous) / Novartis, Genmab
    TARGETING B CELLS IN MULTIPLE SCLEROSIS (ALEXANDRA TRIANTI) -  May 25, 2022 - Abstract #AUTO2022AUTO_257;    
    On the other hand, targeting B cell cytokines with the fusion protein atacicept paradoxically increased MS disease activity, probably by augmenting memory B cells. Finally, essentially all other approved therapies for MS, some of which have been designed to target T cells, have some effects on B cells that may contribute to their therapeutic activity.
  • ||||||||||  evobrutinib (M2951) / EMD Serono, tolebrutinib (SAR442168) / Sanofi
    Preclinical, Journal:  Bruton's tyrosine kinase inhibition in the treatment of preclinical models and multiple sclerosis. (Pubmed Central) -  Apr 7, 2022   
    Thus, the results of ongoing phase 2 and 3 studies with evobrutinib, fenobrutinib, and tolebrutinib in relapsing-remitting and progressive MS are eagerly awaited. This review article introduces the physiological role of BTK, summarizes the pre-clinical and trial evidence, and addresses the potential beneficial effects of BTK inhibition in MS.
  • ||||||||||  tamoxifen / Generic mfg.
    The Role of Human and Mouse BTK in Myeloid Cells ([VIRTUAL]) -  Mar 29, 2022 - Abstract #AAN2022AAN_4206;    
    The BTKi evobrutinib or vehicle was administered to MOG35-55 peptide-immunized C57BL6 mice starting three days after disease onset...BTK was inactivated by crossing mice carrying a floxable BTK allele with mice carrying the Tamoxifen (Tam)-inducible Cre-recombinase under Cx3CR1 promoter...BTK deletion significantly reduced disease severity, demyelination, and axonal damage, demonstrating a role for BTK in tissue-resident myeloid cells in experimental MS. ConclusionstttttttttOverall, these experiments demonstrate that human and mouse myeloid cells may represent a cellular target of BTK inhibitors and that BTK in long-lived myeloid cells supports the expression of neuroinflammation.
  • ||||||||||  tamoxifen / Generic mfg.
    The Role of Human and Mouse BTK in Myeloid Cells (Poster Hall) -  Mar 6, 2022 - Abstract #AAN2022AAN_3098;    
    The BTKi evobrutinib or vehicle was administered to MOG35-55 peptide-immunized C57BL6 mice starting three days after disease onset...BTK was inactivated by crossing mice carrying a floxable BTK allele 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 BTK inhibitors and that BTK in long-lived myeloid cells supports the expression of neuroinflammation.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    New P1 trial:  MS200527_0108: DDI Study of Evobrutinib and Carbamazepine (clinicaltrials.gov) -  Feb 20, 2022   
    P1,  N=18, Recruiting,