- |||||||||| evobrutinib (M2951) / EMD Serono, tolebrutinib (SAR442168) / Sanofi
Bruton's Tyrosine Kinase Inhibitors in Multiple Sclerosis: A Meta-analysis With Reconstructed Individual Patient Data (McCormick Place West | Hall F; In-Person; Virtual) - Mar 5, 2026 - Abstract #AAN2026AAN_3889;
However, their efficacy and safety remain uncertain.Design/A literature search was conducted through PubMed, Scopus, and WOS to identify RCTs evaluating BTK inhibitors (Tolebrutinib; Evobrutinib) in MS. BTK inhibitors showed potential in reducing MRI lesions and disability progression, improving confirmed disability, and demonstrated acceptable safety profile; however, further studies are needed to confirm these findings.
- |||||||||| evobrutinib (M2951) / EMD Serono, Imbruvica (ibrutinib) / AbbVie, J&J
Journal: BTK-Inhibitor Loaded Polymeric Nanoparticles Alleviate Systemic Lupus Erythematosus by Targeting Elimination of Autoreactive BAFFRhigh B Cells. (Pubmed Central) - Jan 28, 2026
Notably, the BTEL nanoparticles could inhibit the survival and activation of B cells, and systemic administration of BTEL could alleviate the development of the lupus mouse model by decreasing the production of anti-dsDNA autoantibodies, along with reduced secretion of inflammatory cytokines and kidney damage, and without apparent side effects. These findings suggest the potential of BTEL in targeting autoreactive B cells, blocking signaling pathways, and improving the efficacy of BTK inhibitors, providing a promising therapeutic approach for SLE, while also reducing toxicity.
- |||||||||| evobrutinib (M2951) / EMD Serono
Bruton's Tyrosine Kinase Regulates Inflammation and Fibrosis in Primary Biliary Cholangitis (Convention Center: Hall DE 4392-4545 Posters) - Oct 7, 2025 - Abstract #AASLD2025AASLD_3412;
To confirm long-term results and determine their role in progressive MS, more phase III trials are necessary. These findings uncover a novel role for BTK in liver fibrosis and support its potential as a therapeutic target in PBC and chronic liver diseases.
- |||||||||| evobrutinib (M2951) / EMD Serono
Bruton's Tyrosine Kinase Inhibition as a Novel Multimodal Therapy for Alcohol-Associated Hepatitis (Convention Center: Hall DE 1481-1657 Posters) - Oct 7, 2025 - Abstract #AASLD2025AASLD_1610;
Alcohol-induced BTK activation occurs in parenchymal and immune cells in the liver and drives steatosis, inflammation, NLRP3 inflammasome activation, and NET formation in AH involving hepatocytes and immune cells. BTK inhibition in multiple cell types may serve as a promising therapeutic strategy for AH.
- |||||||||| evobrutinib (M2951) / EMD Serono
Journal: The contribution of BTK signaling in myeloid cells to neuroinflammation. (Pubmed Central) - Jul 3, 2025
We evaluated i) the impact of the BTK inhibitor (BTKi) evobrutinib on monocyte markers for activation, costimulation, adhesion and phagocytosis in peripheral blood mononuclear cell (PBMC) cultures from healthy and MS subjects; ii) the therapeutic effects and the action of evobrutinib on myeloid cell phenotype in the experimental autoimmune encephalomyelitis (EAE) model of MS; iii) the contribution of BTK in short-lived vs. long-lived myeloid cells to EAE expression via experiments with double transgenic mice allowing inducible inactivation of BTK in CX3CR1 expressing cells...However, conditional BTK deletion in short-lived or long-lived CX3CR1-positive cells did not reduce EAE severity. This functional evidence questions the real contribution of BTK expressing myeloid cells to experimental MS.
- |||||||||| evobrutinib (M2951) / EMD Serono, clemastine / Generic mfg.
Journal: Positive effect of evobrutinib in CNS remyelination models and lack of synergy with clemastine-A dose response study. (Pubmed Central) - Mar 24, 2025
In both experimental models tested no significative improvement on remyelination of co-treatment with evobrutinib plus clemastine was observed. While evobrutinib increased 1.59 fold the number of microglia/macrophages, in the presence of clemastine the number of innate immune cells was decreased by 0.39 fold, therefore counteracting the beneficial effect of microglia/macrophages on remyelination.
- |||||||||| evobrutinib (M2951) / EMD Serono, tolebrutinib (SAR442168) / Sanofi
Preclinical, Journal: Bruton Tyrosine Kinase Inhibition Decreases Inflammation and Differentially Impacts Phagocytosis and Cellular Metabolism in Mouse- and Human-derived Myeloid Cells. (Pubmed Central) - Sep 11, 2024
BTK inhibition resulted in an altered microRNA expression profile (i.e., decreased miR-155-5p and increased miR-223-3p), which is consistent with a decreased proinflammatory myeloid cell phenotype. In summary, these results provide further insights into the mechanism of action of BTK inhibitors in the context of immune-related diseases, while also highlighting important species-specific and cell-specific differences that should be considered when interpreting and comparing results between preclinical and human studies.
- |||||||||| evobrutinib (M2951) / EMD Serono
Journal, IO biomarker: The relation between BTK expression and iron accumulation of myeloid cells in multiple sclerosis. (Pubmed Central) - Aug 16, 2024
BTK inhibition of iron-laden cells dampened the expression of microglia-related inflammatory genes as well as iron-importers, whereas the iron-exporter ferroportin was upregulated. Our data suggest that BTK inhibition not only dampens the proinflammatory response but also reduces iron import and storage in activated microglia and macrophages with possible implications on microglial iron accumulation in chronic active lesions in MS.
- |||||||||| evobrutinib (M2951) / EMD Serono, Mavenclad (cladribine) / EMD Serono
Review, Journal: XVI Post-ECTRIMS Meeting: review of the new developments presented at the 2023 ECTRIMS Congress (II) (Pubmed Central) - Jul 8, 2024
The most recent research on the various treatment algorithms and their efficacy and safety in the management of the disease is reviewed. Finally, the most relevant data for cladribine and evobrutinib are presented, as well as future therapeutic strategies currently being investigated.
- |||||||||| evobrutinib (M2951) / EMD Serono, tolebrutinib (SAR442168) / Sanofi, fenebrutinib (GDC-0853) / Roche
Journal: Bruton tyrosine kinase inhibitors in multiple sclerosis: evidence and expectations. (Pubmed Central) - Apr 29, 2024
Inhibition of BTK has emerged as a promising therapeutic approach to target the CNS-compartmentalized inflammation. Results from phase 3 clinical trials will shed light on differences in efficacy and safety of BTK inhibitors and its potential role in the future MS landscape.
- |||||||||| evobrutinib (M2951) / EMD Serono
Trial completion date, Trial termination: Study of Evobrutinib in Participants With RMS (evolutionRMS 2) (clinicaltrials.gov) - Apr 29, 2024
P3, N=1124, Terminated,
Results from phase 3 clinical trials will shed light on differences in efficacy and safety of BTK inhibitors and its potential role in the future MS landscape. Trial completion date: Jun 2026 --> Mar 2024 | Active, not recruiting --> Terminated; Primary analysis of the RMS phase 3 study (MS200527_0082) resulted in the early termination of the study.
- |||||||||| evobrutinib (M2951) / EMD Serono
Trial completion date, Trial termination: EVOLUTION RMS1: Study of Evobrutinib in Participants With RMS (evolutionRMS 1) (clinicaltrials.gov) - Apr 28, 2024
P3, N=1124, Terminated,
Trial completion date: Jun 2026 --> Mar 2024 | Active, not recruiting --> Terminated; Primary analysis of the RMS phase 3 study (MS200527_0082) resulted in the early termination of the study. Trial completion date: Jun 2026 --> Mar 2024 | Active, not recruiting --> Terminated; Primary analysis of the RMS phase 3 study (MS200527_0080) resulted in the early termination of the study.
- |||||||||| evobrutinib (M2951) / EMD Serono
Trial completion date, Trial termination: MS200527-0086: A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis (clinicaltrials.gov) - Apr 26, 2024
P2, N=267, Terminated,
Trial completion date: Jun 2026 --> Mar 2024 | Active, not recruiting --> Terminated; Primary analysis of the RMS phase 3 study (MS200527_0080) resulted in the early termination of the study. Trial completion date: Feb 2025 --> Apr 2024 | Active, not recruiting --> Terminated; Results from the EVOLUTION clinical trials showed evobrutinib did not meet its primary endpoint of annualized relapse rate for up to 156 weeks compared to oral teriflunomide in both studies.
- |||||||||| evobrutinib (M2951) / EMD Serono
Journal: BTK inhibition limits microglia-perpetuated CNS inflammation and promotes myelin repair. (Pubmed Central) - Apr 24, 2024
Additionally, in a model of toxic demyelination, evobrutinib-mediated BTK inhibition promoted the clearance of myelin debris by microglia, leading to an accelerated remyelination. These findings highlight that BTK inhibition has the potential to counteract underlying chronic progression of MS.
- |||||||||| Mavenclad (cladribine) / EMD Serono
Journal: Update and Application of a Deep Learning Model for the Prediction of Interactions between Drugs Used by Patients with Multiple Sclerosis. (Pubmed Central) - Jan 26, 2024
We also obtained numerous potential interactions for Bruton's tyrosine kinase inhibitors that are in clinical development for MS, such as evobrutinib (n = 434 DDIs)...We demonstrate that deep learning techniques can exploit chemical structure similarity to accurately predict DDIs and DFIs in patients with MS. Our study specifies drug pairs that potentially interact, suggests mechanisms causing adverse drug effects, informs about whether interacting drugs can be replaced with alternative drugs to avoid critical DDIs and provides dietary recommendations for MS patients who are taking certain drugs.
- |||||||||| evobrutinib (M2951) / EMD Serono, Mavenclad (cladribine) / EMD Serono
Review, Journal: 15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II) (Pubmed Central) - Jul 9, 2023
It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.
- |||||||||| evobrutinib (M2951) / EMD Serono
Review, Journal: Bruton's tyrosine kinase as a promising therapeutic target for multiple sclerosis. (Pubmed Central) - Jun 14, 2023
This reflects the emerging concept that the underlying pathophysiology of chronic progressive MS differs from that of relapsing-remitting MS. Understanding the CNS intrinsic process in more detail provides novel therapeutic targets, and one of these may be the inhibition of the enzyme BTK.
- |||||||||| Brukinsa (zanubrutinib) / BeiGene
Preclinical, Journal: Anticancer effect of zanubrutinib in HER2-positive breast cancer cell lines. (Pubmed Central) - May 1, 2023
Small molecule Bruton's tyrosine kinase (BTK) inhibitors have been developed for the treatment of various haemato-oncological diseases, and ibrutinib was approved as the first BTK inhibitor for anticancer therapy in 2013...Based on their similar kinase selectivity profiles, we investigated the anticancer effect of zanubrutinib, evobrutinib, tirabrutinib and acalabrutinib in different BCa cell lines and sought to determine whether it is linked with targeting the epidermal growth factor receptor family (ERBB) pathway...Zanubrutinib effectively inhibits the phosphorylation of proteins in the ERBB signalling cascade, including the downstream kinases Akt and ERK, which mediate key signals ensuring the survival and proliferation of cancer cells. We thus propose zanubrutinib as another suitable candidate for repurposing in HER2-amplified solid tumours.
- |||||||||| evobrutinib (M2951) / EMD Serono
IN VIVO BRUTON (S403 - McCormick Place) - Mar 23, 2023 - Abstract #DDW2023DDW_5832;
Some mice received oral gavage of Evobrutinib, a BTK inhibitor (BTKi) or DMSO from day7 to day10... Our findings define a novel role of BTK in regulating CD84 phosphorylation and granulopoiesis that could be harnessed to address pressing therapeutic needs in AH.
- |||||||||| evobrutinib (M2951) / EMD Serono
Trial completion, Trial completion date, Trial primary completion date: MS200527_0091: Study Comparing Pharmacokinetics of Different Formulations of Evobrutinib in Healthy Participants (clinicaltrials.gov) - Mar 22, 2023
P1, N=58, Completed,
Our findings define a novel role of BTK in regulating CD84 phosphorylation and granulopoiesis that could be harnessed to address pressing therapeutic needs in AH. Recruiting --> Completed | Trial completion date: Aug 2022 --> Feb 2023 | Trial primary completion date: Aug 2022 --> Feb 2023
- |||||||||| tolebrutinib (SAR442168) / Sanofi
Comparative CNS Pharmacology of Tolebrutinib Versus Other BTK Inhibitor Candidates for Treating MS (Both in-person and online) - Mar 12, 2023 - Abstract #AAN2023AAN_4366;
Conclusions Next-generation drug candidates in MS must achieve pharmacologically-relevant concentrations in the CNS to address the existing treatment gap. In these NHP experiments, tolebrutinib was the only BTK inhibitor to show bioactive CSF levels, adding to the evidence that tolebrutinib has potential to slow disability accumulation via modulating neuroinflammation.
- |||||||||| evobrutinib (M2951) / EMD Serono
Efficacy and Safety of the Bruton (Both in-person and online) - Mar 12, 2023 - Abstract #AAN2023AAN_2290;
P2
Conclusions The pre- and post-switch ARR data support that BID dosing (75mg fasted, comparable to 45mg BID fed in Phase III) provides maximal efficacy on clinical endpoints. Evobrutinib, over 3.5 years in the OLE, continues to show maintained treatment benefits and acceptable tolerability, with no new safety signals.
- |||||||||| evobrutinib (M2951) / EMD Serono
The Bruton (Both in-person and online) - Mar 12, 2023 - Abstract #AAN2023AAN_2286;
The limited effect of anti-CD20 treatment confirms the insufficient disease inhibition potential of antibody-based therapies when targeting intrathecal B cells. These findings support the notion that evobrutinib targets persistent neuroinflammation in MS.
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