^
    2d
    Involvement of Btk in Cardiovascular Disease and Its Therapeutic Targeting. (PubMed, Circulation)
    First-generation BTKi such as ibrutinib demonstrate antithrombotic efficacy but are limited by off-target effects, including bleeding and atrial fibrillation. Second- and third-generation inhibitors (eg, acalabrutinib, zanubrutinib, and pirtobrutinib) show enhanced selectivity, reducing cardiovascular toxicity in patients with B-cell malignancies. Highly selective BTKi (fenebrutinib and remibrutinib) do not show bleeding in clinical trials of various autoimmune disorders, and covalent selective BTKi applied at low dosage are expected to selectively inhibit Btk in platelets without bleeding side effects. Preclinical data and early observations from compassionate use in patients with atypical autoimmune thrombosis highlight the potential of BTKi as selective antithrombotic agents beyond traditional therapies. This review conceptualizes and underscores Btk's pivotal role at immune-thrombosis interfaces in atherothrombosis, advocating for precision medicine approaches and innovative platforms to unlock its full therapeutic potential in cardiovascular disease management.
    Review • Journal
    |
    NLRP3 (NLR Family Pyrin Domain Containing 3)
    |
    Imbruvica (ibrutinib) • Brukinsa (zanubrutinib) • Calquence (acalabrutinib) • Jaypirca (pirtobrutinib) • Rhapsido (remibrutinib) • fenebrutinib (RG7845)
    5ms
    FENerations1: A Pharmacokinetics (PK), Pharmacodynamics (PD), Safety and Tolerability Study of Fenebrutinib in Children and Adolescents With Relapsing Multiple Sclerosis (RMS) (clinicaltrials.gov)
    P2, N=12, Recruiting, Hoffmann-La Roche
    New P2 trial
    |
    fenebrutinib (RG7845)
    8ms
    FENhance 2: Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS) (clinicaltrials.gov)
    P3, N=751, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Nov 2025 --> Jul 2027
    Trial completion date
    |
    fenebrutinib (RG7845)
    9ms
    FENhance: A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS) (clinicaltrials.gov)
    P3, N=746, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Nov 2025 --> Nov 2027 | Trial primary completion date: Oct 2025 --> Jan 2026
    Trial completion date • Trial primary completion date
    |
    fenebrutinib (RG7845)
    9ms
    FENtrepid: A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis (clinicaltrials.gov)
    P3, N=985, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Dec 2026 --> Jul 2027 | Trial primary completion date: Jan 2026 --> Sep 2025
    Trial completion date • Trial primary completion date
    |
    Ocrevus (ocrelizumab) • fenebrutinib (RG7845)
    almost2years
    FENhance: A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS) (clinicaltrials.gov)
    P3, N=746, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    fenebrutinib (RG7845)
    2years
    Network-Based In Silico Analysis of New Combinations of Modern Drug Targets with Methotrexate for Response-Based Treatment of Rheumatoid Arthritis. (PubMed, J Pers Med)
    New game-changing drugs including Mavrilimumab, Iguratimod, Upadacitinib, Fenebrutinib, and nanoparticles may be crucial in controlling symptoms in poorly managed RA patients. Emerging therapeutic targets like Toll-like 4 receptors, NLRP3 inflammasome complexes, and mesenchymal stem cells can further transform RA therapy.
    Review • Journal
    |
    TYMS (Thymidylate Synthetase) • SYK (Spleen tyrosine kinase) • NLRP3 (NLR Family Pyrin Domain Containing 3)
    |
    Rituxan (rituximab) • methotrexate • hydroxychloroquine • Actemra IV (tocilizumab) • fenebrutinib (RG7845) • leflunomide • mavrilimumab (KPL-301)
    2years
    FENhance 2: Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS) (clinicaltrials.gov)
    P3, N=751, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    NEFL (Neurofilament Light Chain)
    |
    fenebrutinib (RG7845)
    over2years
    Discovery of Novel Bruton's Tyrosine Kinase PROTACs with Enhanced Selectivity and Cellular Efficacy. (PubMed, J Med Chem)
    Here, we disclose the discovery and in vitro characterization of BTK PROTACs based on the selective BTK inhibitor GDC-0853 and the cereblon recruitment ligand pomalidomide. PTD10 is a highly potent BTK degrader (DC 0.5 nM) that inhibited cell growth and induced apoptosis at lower concentrations than the two parent molecules, as well as three previously reported BTK PROTACs, and had improved selectivity compared to ibrutinib-based BTK PROTACs.
    Journal
    |
    BTK (Bruton Tyrosine Kinase) • CRBN (Cereblon)
    |
    Imbruvica (ibrutinib) • pomalidomide • fenebrutinib (RG7845)
    over3years
    Novel BTK Mutations Conferring Resistance to Non-Covalent BTK Inhibitors and Alternative Treatment Strategy (ASH 2022)
    Here,we generated and comprehensively characterized BTK and PLCG2 mutations conferring resistance to ibrutinib and five different non-covalent BTKi namely pirtobrutinib (LOXO-305), vecabrutinib (SNS-062), nemtabrutinib (ARQ-531), fenebrutinib (GDC-0853), and RN-486. We also found that cells harboring these novel BTK mutations showed differential sensitivity to the covalent vs. non-covalent BTKi. We further demonstrate the potential of venetoclax as follow up treatment upon resistance to non-covalent BTKi.
    IO biomarker
    |
    PLCG2 (Phospholipase C Gamma 2)
    |
    PLCG2 mutation • BTK mutation • BTK L845F • PLCG2 L845F
    |
    Venclexta (venetoclax) • Imbruvica (ibrutinib) • Jaypirca (pirtobrutinib) • vecabrutinib (SNS-062) • RN486 • fenebrutinib (RG7845) • nemtabrutinib (MK-1026)