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


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  • ||||||||||  Review, Journal:  Bleeding by Bruton Tyrosine Kinase-Inhibitors: Dependency on Drug Type and Disease. (Pubmed Central) -  Apr 7, 2021   
    Remibrutinib, a novel highly selective covalent BTKi, is currently in clinical studies of autoimmune dermatological disorders...By focusing on their pharmacological properties, targeted disease, bleeding side effects and actions on platelets it attempts to clarify the mechanisms underlying bleeding. Specific platelet function tests in blood might help to estimate the probability of bleeding of newly developed BTKi.
  • ||||||||||  Review, Journal, Adverse events:  Comparative Analysis of BTK Inhibitors and Mechanisms Underlying Adverse Effects. (Pubmed Central) -  Mar 30, 2021   
    Next-generation inhibitors, acalabrutinib and zanubrutinib, are approved both in the United States and in Europe, and zanubrutinib also in China, while tirabrutinib is currently only registered in Japan...However, an increasing number of trials instead addresses autoimmunity and inflammation in multiple sclerosis, rheumatoid arthritis, pemphigus and systemic lupus erythematosus with the use of either irreversibly binding inhibitors, e.g., evobrutinib and tolebrutinib, or reversibly binding inhibitors, like fenebrutinib...Moreover, dermatological toxicities, diarrhoea, bleedings and invasive fungal infections often develop early after BTKi treatment initiation and subsequently subside. Conversely, cardiovascular AEs, like hypertension and various forms of heart disease, often persist.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Journal:  Inhibition of Bruton´s tyrosine kinase as a novel therapeutic approach in multiple sclerosis. (Pubmed Central) -  Mar 4, 2021   
    We searched PubMed or clinicaltrials.gov for the terms 'BTK inhibition' or 'Bruton´s Tyrosine Kinase' or 'anti-CD20' and 'Multiple Sclerosis' Expert opinion: BTK inhibition has shown effectiveness in preclinical models of CNS disease and MS clinical trials. Further studies are necessary to differentiate this approach from B cell depletion and to position it in the armamentarium of therapeutics.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment open:  MS200527_0063: Drug-drug Interaction Study of Evobrutinib With Midazolam in Healthy Participants (clinicaltrials.gov) -  Jan 21, 2021   
    P1,  N=18, Recruiting, 
    Further studies are necessary to differentiate this approach from B cell depletion and to position it in the armamentarium of therapeutics. Not yet recruiting --> Recruiting
  • ||||||||||  Arzerra (ofatumumab) / Novartis, Genmab, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    Review, Journal:  Targeting B cells to modify MS, NMOSD, and MOGAD: Part 2. (Pubmed Central) -  Jan 14, 2021   
    The safety profile of long-term B-cell depletion in MS, NMOSD, and MOGAD will be highlighted. Finally implications of the current coronavirus disease 2019 pandemic on the management of patients with these disorders and the use of B cell-depleting agents will be discussed.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment open:  MS200527_0059: Effect of Hepatic Impairment on M2951 (BTK Inhibitor) PK (clinicaltrials.gov) -  Oct 8, 2020   
    P1,  N=28, Recruiting, 
    Previous publication of these data: These data were presented for the first time at MS Virtual 2020: 8th Joint ACTRIMS/ECTRIMS Meeting, September 9–12, 2020. Not yet recruiting --> Recruiting
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Trial completion date, Trial termination:  MS200527-0018: A Phase II Study of M2951 in SLE (clinicaltrials.gov) -  Aug 27, 2020   
    P2,  N=480, Terminated, 
    No abstract available Trial completion date: Aug 2022 --> Mar 2020 | Active, not recruiting --> Terminated; Study is completed; primary analysis completed.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    [VIRTUAL] The Bruton’s tyrosine kinase inhibitor evobrutinib ameliorates meningeal inflammation in experimental autoimmune encephalomyelitis () -  Aug 25, 2020 - Abstract #MSDC2020MSDC_1390;    
    A significant decrease in B cells in areas of meningeal inflammation in the evobrutinib group compared to the vehicle group was noted. Also, astrocytosis in the adjacent cortex was reduced in the evobrutinib group compared with vehicle.Conclusions An amelioration of established meningeal inflammation, as assessed by imaging and pathological measures, in a relapsing–remitting EAE model was observed with evobrutinib treatment, suggesting the potential utility of this agent to target this phenomenon in MS patients.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    [VIRTUAL] T-bet+ B-cell development in MS: Association with Bruton’s Tyrosine Kinase activity and targeting by evobrutinib () -  Aug 16, 2020 - Abstract #MSDC2020MSDC_482;    
    P2
    Moreover, the relation between BTK activity and T-bet+ B-cell differentiation was assessed both ex vivo and in vitro.Methods We determined BTK and phosphorylated BTK (pBTK) levels in transitional, naive mature, class-switched and non class-switched B cells in blood from both treatment-naive patients with CIS, RRMS, SPMS and PPMS and healthy controls (HC; n=30 per group), as well as clinical MS responders and non-responders to natalizumab (pre- vs 1y post-treatment) using flow cytometry...T-bet and T-bet-related markers (CD21, CD11c) were only affected by evobrutinib in IFN-γ- and TLR9-stimulating naive B-cell cultures.Conclusions These data demonstrate that BTK is more activated in memory B cells from RRMS and SPMS patients and functionally related to pathogenic T-bet+ B-cell development. This study provides new mechanistic insights into how evobrutinib intervenes in human B-cell differentiation and can modulate the clinical course of MS.
  • ||||||||||  fenebrutinib (GDC-0853) / Roche
    [VIRTUAL] Fenebrutinib, a noncovalent, highly selective, long residence time investigational Btk inhibitor for the treatment of MS () -  Aug 16, 2020 - Abstract #MSDC2020MSDC_424;    
    Finally, in a preincubation-dilution assay, the Btk•FEN complex is very stable; FEN dissociates very slowly from Btk and shows a residence time of 18.3 hours bound to Btk.Conclusions The high selectivity and potency of FEN has the potential to be associated with fewer off-target adverse events and an improved MS therapeutic index compared with less selective Btk inhibitors. FEN’s long residence time bound to Btk may also improve the MS therapeutic index by mimicking the durable pharmacological inhibition of a covalent inhibitor but without the safety risks of covalent Btk inhibitors.
  • ||||||||||  Leustatin (cladribine) / J&J, Tecfidera (dimethyl fumarate) / Biogen, Mavenclad (cladribine) / EMD Serono
    Review, Journal:  Advances in oral immunomodulating therapies in relapsing multiple sclerosis. (Pubmed Central) -  Jul 10, 2020   
    The oral immunomodulator laquinimod did not reach the primary endpoint of reduction in confirmed disability progression in a phase 3 trial of patients with relapsing multiple sclerosis...This treatment scheme might lead to higher efficacy but also to new safety concerns. These sequential treatments were largely excluded in phase 2 and 3 trials; therefore, monitoring both short-term and long-term effects of sequential disease-modifying therapies in phase 4 studies, cohort studies, and registries will be necessary.
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment open:  EVOLUTION RMS1: Study of Evobrutinib in Participants With RMS (evolutionRMS 1) (clinicaltrials.gov) -  Jul 1, 2020   
    P3,  N=930, Recruiting, 
    Clinical investigation of evobrutinib is ongoing in several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. Not yet recruiting --> Recruiting
  • ||||||||||  evobrutinib (M2951) / EMD Serono
    Enrollment open:  Study of Evobrutinib in Participants With RMS (evolutionRMS 2) (clinicaltrials.gov) -  Jul 1, 2020   
    P3,  N=930, Recruiting, 
    Not yet recruiting --> Recruiting Not yet recruiting --> Recruiting
  • ||||||||||  evobrutinib (M2951) / EMD Serono, Rebif (human IFN-?-1a) / EMD Serono
    Enrollment change, Trial completion date, Trial termination, Trial primary completion date:  EVOLUTION MS1: Study of Evobrutinib in Participants With Relapsing Multiple Sclerosis (RMS) (clinicaltrials.gov) -  Jun 1, 2020   
    P3,  N=3, Terminated, 
    N=950 --> 3 | Trial completion date: Oct 2026 --> Apr 2020 | Recruiting --> Terminated | Trial primary completion date: Sep 2023 --> Apr 2020; Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0073. Consequently, this trial terminated early.
  • ||||||||||  evobrutinib (M2951) / EMD Serono, Rebif (human IFN-?-1a) / EMD Serono
    Enrollment change, Trial completion date, Trial termination, Trial primary completion date:  EVOLUTION MS2: Study of Evobrutinib in Participants With RMS (clinicaltrials.gov) -  May 31, 2020   
    P3,  N=1, Terminated, 
    N=950 --> 1 | Trial completion date: Jun 2023 --> May 2020 | Not yet recruiting --> Terminated | Trial primary completion date: Jun 2023 --> May 2020; Following analysis of open label extension (OLE) data from RMS phase 2 study (MS200527- 0086), it was determined that a change in active comparator warranted in phase 3 RMS comprised of trial MS200527-0074. Consequently, this trial terminated early.