{"entity":{"id":"zanubrutinib","kind":"drug","name":"Zanubrutinib","aka":[],"tldr":"Zanubrutinib is the only BTK blocker to beat ibrutinib on both efficacy and safety in a head-to-head trial. It is now the most prescribed BTK inhibitor in CLL.","summary":"ALPINE (relapsed CLL): PFS superior to ibrutinib (HR 0.65) with less atrial fibrillation; SEQUOIA (frontline): PFS superior to bendamustine-rituximab, 5-year PFS 72% in del(17p); SEQUOIA arm D (zanubrutinib + venetoclax) uMRD ~60%. Approved in CLL January 2023. Also MCL, Waldenström, MZL, follicular lymphoma. BeOne is testing zanubrutinib + sonrotoclax (CELESTIAL-TNCLL) and the BTK degrader BGB-16673 as successors.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Zanubrutinib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Zanubrutinib"}],"tags":[],"related":[],"cancers":["cll","dlbcl","marginal-zone-lymphoma","cll-treatment-naive"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["btk"],"drugs":[],"companies":["beone"],"institutions":[],"pathways":[],"terms":[],"trials":["alpine","sequoia","celestial-tncll","nct04002297","nct06742996","nct05100862","nct06697184","nct07277231","nct06634589","nct04170283","nct06375733","nct04662255","nct06637501","nct05952037"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Brukinsa","modality":"Small-molecule covalent BTK inhibitor (second generation)","mechanism":"Covalent BTK inhibitor with sustained near-complete BTK occupancy in lymph nodes and fewer off-target kinases than ibrutinib.","approvals":[{"region":"US","year":2019,"indication":"Relapsed MCL (accelerated)"},{"region":"US","year":2023,"indication":"CLL/SLL, all lines (SEQUOIA, ALPINE)"}],"mechanismSteps":["Twice-daily dosing keeps BTK occupancy >95% in nodes throughout the day","BCR signalling and CXCR4-mediated homing are blocked","CLL cells exit protective niches and die","Lower EGFR/ITK inhibition means fewer cardiac and bleeding events"],"dosing":{"route":"Oral","schedule":"160 mg twice daily or 320 mg once daily, continuously","monitoring":"Infections, cytopenias, bleeding, atrial fibrillation (lower than ibrutinib), hypertension","source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Brukinsa"},"toxicity":[{"event":"Atrial fibrillation/flutter","anyGradePct":5.2,"source":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Brukinsa","note":"ALPINE vs 13.3% ibrutinib"},{"event":"Neutropenia","grade3PlusPct":16},{"event":"Hypertension","anyGradePct":23},{"event":"Upper respiratory infection","anyGradePct":27}],"access":[],"regulatoryEvents":[{"date":"2019-11-14","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 6.8 years later, when the FDA's table was read.","indication":"Treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy."},{"date":"2021-09-14","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 5.0 years later, when the FDA's table was read.","indication":"Treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen"},{"date":"2023-01-19","type":"approval","region":"US","note":"CLL/SLL","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2024-03-07","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 2.5 years later, when the FDA's table was read.","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zanubrutinib-relapsed-or-refractory-follicular-lymphoma","indication":"Adult patients with relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy"},{"date":"2025-06-10","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 1.3 years later, when the FDA's table was read.","indication":"Formulation: Treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy."},{"date":"2025-06-10","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 1.3 years later, when the FDA's table was read.","indication":"Formulation: Treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen."},{"date":"2025-06-10","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint; the confirmatory requirement was still open 1.3 years later, when the FDA's table was read.","indication":"Formulation: Treatment of adult patients with relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy."}]},"route":"/drugs/zanubrutinib/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic leukaemia, first treatment","route":"/cancers/cll-treatment-naive/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"malt-lymphoma","kind":"cancer","name":"Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)","route":"/cancers/malt-lymphoma/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-lymphoma/"},{"id":"nodal-marginal-zone-lymphoma","kind":"cancer","name":"Nodal marginal zone 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(MCL)","route":"/trials/nct04662255/"}],"term":[{"id":"btki-bcl2i-resistance-mutations","kind":"term","name":"BTK C481S, PLCG2 and BCL2 G101V resistance mutations","route":"/terms/btki-bcl2i-resistance-mutations/"},{"id":"cll-ipi","kind":"term","name":"CLL-IPI (chronic lymphocytic leukaemia prognostic index)","route":"/terms/cll-ipi/"},{"id":"mipi","kind":"term","name":"MIPI (Mantle Cell Lymphoma International Prognostic Index)","route":"/terms/mipi/"},{"id":"myd88-l265p","kind":"term","name":"MYD88 L265P and CXCR4 mutations","route":"/terms/myd88-l265p/"},{"id":"richter-transformation","kind":"term","name":"Richter transformation","route":"/terms/richter-transformation/"},{"id":"tki-term","kind":"term","name":"Tyrosine kinase inhibitor (TKI)","route":"/terms/tki-term/"},{"id":"lymphoma-tx-uk-access","kind":"term","name":"What the NHS in England funds for lymphoma, appraisal by 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