{"id":6851,"date":"2024-12-06T13:03:54","date_gmt":"2024-12-06T12:03:54","guid":{"rendered":"https:\/\/beigen.vipdev.lndo.site\/us\/?post_type=compound&p=6851"},"modified":"2025-10-20T16:57:56","modified_gmt":"2025-10-20T14:57:56","slug":"zanubrutinib","status":"publish","type":"compound","link":"https:\/\/beonemedaffairs.com\/us\/compound\/6851\/zanubrutinib\/","title":{"rendered":"Zanubrutinib"},"content":{"rendered":"","protected":false},"template":"","meta":{"_acf_changed":false,"editor_notices":[]},"post-tag":[542],"class_list":["post-6851","compound","type-compound","status-publish","hentry","post-tag-zanubrutinib","disease_state-b-cell-malignancies","disease_state-chronic-lymphocytic-leukemia","disease_state-diffuse-large-b-cell-lymphoma","disease_state-follicular-lymphoma","disease_state-hematologic-malignancies","disease_state-mantle-cell-lymphoma","disease_state-marginal-zone-lymphoma","disease_state-small-lymphocytic-lymphoma","disease_state-waldenstroms-macroglobulinemia","molecule-zanubrutinib"],"acf":{"header_text":"Zanubrutinib is a next-generation Bruton\u2019s tyrosine kinase inhibitor (BTKi) designed for selectivity, potency, and bioavailability.","summary":"Zanubrutinib is a next-generation Bruton\u2019s tyrosine kinase inhibitor (BTKi) designed for selectivity, potency, and bioavailability.","tags":[542],"text":"","approval_status_for_filter":"approved","accordion_presentation":"expanded","overview":"Zanubrutinib is a potent and highly selective small molecule inhibitor of Bruton\u2019s tyrosine kinase (BTK), with demonstrated near complete BTK occupancy in peripheral blood mononuclear cells (PBMCs).1<\/sup> It has exposure coverage above its IC50<\/sub> during the entire dose interval for both BID and QD dosing schedules.2<\/sup>\r\n\r\nZanubrutinib is currently being evaluated in over 35 trials across 29 countries. In head-to-head clinical trials, zanubrutinib demonstrated a more favorable safety profile with fewer cardiovascular toxicities than ibrutinib.\u00a0 Zanubrutinib\u2019s non-cardiac safety profile is consistent with that reported for other BTKis.3,4<\/sup> Zanubrutinib is the only BTKi with proven superiority of PFS vs ibrutinib in the ALPINE trial, which included high-risk relapsed\/refractory chronic lymphocytic leukemia (CLL) patients with del(17p)\/TP53<\/em> and uIGHV.3<\/sup>\r\n\r\nZanubrutinib combination studies include sonrotoclax (BCL2 inhibitor), tislelizumab (anti-PD-1 mAb), BGB-10188 (PI3K\u03b4 inhibitor), obinutuzumab (anti-CD-20 mAb), rituximab (anti-CD-20 mAb), lenalidomide + rituximab, and venetoclax (BCL2 inhibitor).\r\n\r\nReferences<\/strong>\r\n
    \r\n \t
  1. Tam, C. S. et al. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood<\/em> 2019;134:851\u2013859.<\/li>\r\n \t
  2. Tam, C. S., Ou, Y. C., Trotman, J. & Opat, S. Clinical pharmacology and PK\/PD translation of the second-generation Bruton\u2019s tyrosine kinase inhibitor, zanubrutinib. Expert Rev. Clin. Pharmacol<\/em> 2021;14(11):1329-1344.<\/li>\r\n \t
  3. Brown, J. R. et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R\/R CLL\/SLL: Final comparative analysis of ALPINE. Blood<\/em> 2024; blood.2024024667.<\/li>\r\n \t
  4. Dimopoulos, M. A, et al. Zanubrutinib versus ibrutinib in symptomatic Waldenstr\u00f6m macroglobulinemia: Final analysis from the randomized phase III ASPEN study. J. Clin. Oncol. 2023;41(33):5099-5106.<\/li>\r\n<\/ol>","mechanism_of_action":"Bruton\u2019s tyrosine kinase (BTK) is a component of the B-cell receptor (BCR) signaling pathway and is an important regulator of cell proliferation and cell survival in various B cell malignancies including chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL\/SLL), Waldenstr\u00f6m\u2019s macroglobulinemia (WM) and marginal zone lymphoma (MZL). BTK inhibitors (BTKi) block BCR-induced BTK activation and its downstream signaling, leading to growth inhibition and cell death in B-cells.1<\/sup>\r\n\r\nZanubrutinib is an orally active inhibitor that covalently binds cysteine 481 in the adenosine triphosphate (ATP) binding pocket of BTK leading to irreversible inactivation of the enzyme.2<\/sup> Zanubrutinib was designed to minimize off-target inhibition of TEC and EGFR family kinases. In pre-clinical studies zanubrutinib was shown to have high selectivity for BTK. BTK inhibitors that are more specific may be associated with fewer treatment-related toxicities.2<\/sup>\r\n\r\n\"\"\r\n\r\nReferences <\/strong>\r\n
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    1. Pal Singh, S., Dammeijer, F. & Hendriks, R. W. Role of Bruton\u2019s tyrosine kinase in B cells and malignancies. Mol. Cancer<\/em> 2018;17:57.<\/li>\r\n \t
    2. Tam, C. S. et al.<\/em> Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood<\/em> 2019;134:851\u2013859.<\/li>\r\n<\/ol>","approval_status":"Zanubrutinib is indicated for the treatment of adult patients with:\r\n