Ibrutinib

SAN CARLOS, Calif.--(BUSINESS WIRE)--BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology company, reaffirms its position as the leader in chronic lymphocytic leukemia (CLL) innovation by showcasing the depth, quality, and momentum of its hematology portfolio at the 67th ASH Annual Meeting and Exposition in Orlando, Florida. The totality of BeOne’s ASH data reinforce BRUKINSA® (zanubrutinib) as the foundational Bruton’s tyrosine kinase inhibitor (BTKi) of choice. “At ASH 2025, we will present new data from across our CLL franchise, highlighting both the strength of BRUKINSA and the potential of BGB-16673,” said Amit Agarwal, M.D., Ph.D., Chief Medical Officer, Hematology, BeOne. “Long-term data are the gold standard in CLL, and BRUKINSA continues to deliver the high levels of durable progression-free and overall survival that patients and physicians should demand from a BTK inhibitor. BGB-16673, the most advanced BTK degrader in the clinic with over 800 patients dosed to date, potentially represents the next wave of foundational innovation in oncology.” BRUKINSA continues to demonstrate unprecedented long-term efficacy with a favorable safety profile over more than six years of follow-up in treatment-naïve CLL/SLL. In SEQUOIA (NCT03336333), a randomized, multicenter, global Phase 3 trial, BRUKINSA maintained progression-free survival (PFS) superiority versus bendamustine plus rituximab (BR) with an estimated 74% PFS at six years in treatment-naïve CLL or small lymphocytic lymphoma (SLL) compared with 32% PFS for BR. Highlights include: COVID-19 adjusted PFS rates were 77% (95% CI, 70.1-81.8) for BRUKINSA and 33% (95% CI, 25.5-40.4) for BR. The overall survival (OS) at 72 months was 84% for BRUKINSA and 80% with BR. After adjusting for COVID-19, the OS rates were 88% and 82%, respectively. In patients with del(17p), the six-year PFS was 64% (65% after COVID-19 adjustment) and the 72-month OS was 83%. The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified. “SEQUOIA’s longer follow-up strengthens the evidence for continuous zanubrutinib use,” said Constantine Tam, M.B.B.S., M.D., Head of Lymphoma Service at Alfred Health and Professor of Haematology at Monash University. “Patients continued to show durable disease control and consistent safety across study arms, meaningfully raising the bar for CLL patients, including those with harder-to-treat CLL.” In the overall patient population, in which 58% of patients had del(17p) and/or TP53 mutation, the median PFS was not reached; the 36-month PFS rate was 87%. The 36-month PFS rate for patients with del(17p) and/or TP53 mutation was 87% and for patients without del(17p) and TP53 mutation was 89%. A total of 42 patients completed the BRUKINSA plus venetoclax combination and continued BRUKINSA monotherapy. At 12 months following the combination period, peripheral blood undetectable minimal residual disease (uMRD) was maintained in 100% (18/18) of patients without del(17p) and TP53 . At 18 months following the combination period, uMRD was maintained in 92% (22/24) of patients with del(17p) and/or TP53 mutation. The safety profile of BRUKINSA plus venetoclax was generally tolerable and no unexpected safety signals were identified. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ® ) now recommend zanubrutinib plus venetoclax as a preferred first-line regimen for CLL/SLL. New patient-reported outcomes data in R/R CLL suggest BRUKINSA may offer a more manageable side effect profile. Up to six-years of follow-up data support BRUKINSA’s foundational role in CLL/SLL as the only BTK inhibitor with enduring PFS and long-term benefit over another BTK inhibitor. ALPINE (NCT03734016) is a global, randomized, open-label, multicenter, Phase 3 study of BRUKINSA versus ibrutinib in patients with R/R CLL/SLL who received ≥1 prior systemic therapy. Highlights include: This study is among the first analyses of patients with CLL/SLL to demonstrate a statistically and clinically meaningful association between longitudinal symptom deterioration and disease progression using joint modeling. Deterioration in patient-reported fatigue, insomnia, and nausea/vomiting emerged as strong symptomatic indicators of disease progression. Compared with ibrutinib, patients on BRUKINSA showed reduced risk of symptom deterioration associated with earlier disease progression. The analysis showed that patients on BRUKINSA had lower odds of symptom worsening for nausea/vomiting, fatigue, pain, and insomnia. With up to 73.5 months of follow-up, the median PFS for all patients was a striking 52.5 months; the 60-month PFS rate was 47.3% (50.4% adjusted for COVID-19). These results redefine what is expected for this patient population. Among patients with del(17p), the median PFS was 49.9 months; the 60-month PFS rate was 38.2% (40.5% adjusted for COVID-19). With longer follow-up, the prevalence of most adverse events of special interest remained stable year-over-year. BGB-16673 (BTK degrader) clinical data demonstrates rapid, robust and deepening responses in patients with heavily pretreated R/R CLL/SLL, including those with prior BTKi treatment and mutations that confer resistance to BTK inhibitors. (Oral Presentation: 85) Updated results from CaDAnCe-101 (NCT05006716), an ongoing open-label, Phase 1/2 study evaluating BGB-16673 monotherapy in patients with B-cell malignancies, showed responses across R/R CLL/SLL patient types, including those who had previously been treated with BTK inhibitors, BCL2 inhibitors, noncovalent BTK inhibitors, and those with BTK inhibitor resistance mutations. Highlights include: With a median follow-up of 19.8 months, 54.4% of patients remain on treatment. Across all doses, ORR was 85.3% and CR/CR with incomplete count recovery (CRi) rate was 2.9% with responses deepening over time. In the group of patients dosed at the recommended phase 2 dose (RP2D; 200 mg QD), ORR was 94.4%. In the patients with prior covalent BTK inhibitor, BCL2i, and noncovalent BTK inhibitor treatment, ORR was 75.0%. In the group of patients dosed at the recommended phase 2 dose (RP2D; 200 mg QD), ORR was 94.4%. In the patients with prior covalent BTK inhibitor, BCL2i, and noncovalent BTK inhibitor treatment, ORR was 75.0%. The 12- and 18-month PFS rates were 73.5% and 65.9% respectively. BGB-16673 was generally well tolerated in this heavily pretreated population with no treatment-related deaths and no new toxicities identified with a median treatment duration of 13.6 months. For more information about our presence at the 2025 ASH Annual Meeting and Exposition, please visit our meeting hub: congress.beonemedicines.com. About Chronic Lymphocytic Leukemia Chronic lymphocytic leukemia (CLL) is a life-threatening cancer of adults. It is a type of mature B-cell malignancy in which abnormal leukemic B lymphocytes (a type of white blood cells) arise from the bone marrow and flood peripheral blood, bone marrow, and lymphoid tissues.1,2 CLL is the most common type of leukemia in adults, accounting for about one-third of new cases.2,3 About BGB-16673 BGB-16673 is a potential first-in-class Bruton’s tyrosine kinase (BTK) protein degrader and is the most advanced protein degrader in the clinic, with nearly 800 patients dosed to date in an extensive global clinical development program. This program includes three randomized Phase 3 trials in R/R CLL, including the head-to-head Phase 3 trial versus pirtobrutinib, which began enrolling in Q4 2025. Originating from BeOne’s chimeric degradation activation compound (CDAC) platform, BGB-16673 is designed to promote the degradation, or breakdown, of both wildtype and mutant forms of BTK, including those that commonly result in resistance to BTK inhibitors in patients who experience progressive disease. The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to BGB-16673 for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), and adult patients with R/R mantle cell lymphoma (MCL). Additionally, the European Medicines Agency (EMA) granted BGB-16673 PRIority MEdicines (PRIME) designation for the treatment of patients with Waldenstrom’s macroglobulinemia (WM) previously treated with a BTK inhibitor. About BRUKINSA® (zanubrutinib) BRUKINSA is an orally available, small molecule inhibitor of Bruton’s tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues. BRUKINSA has the broadest label globally of any BTK inhibitor and is the only BTK inhibitor to provide the flexibility of once or twice daily dosing. BRUKINSA is also the only BTK inhibitor to demonstrate superiority to another BTK inhibitor in a Phase 3 study. The global BRUKINSA clinical development program includes about 7,100 patients enrolled in 30 countries and regions across more than 35 trials. BRUKINSA is approved in more than 75 markets, and more than 247,000 patients have been treated globally. Select Important Safety Information Serious adverse reactions, including fatal events, have occurred with BRUKINSA, including hemorrhage, infections, cytopenias, second primary malignancies, cardiac arrhythmias, and hepatotoxicity (including drug-induced liver injury). In the pooled safety population (N=1729), the most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA were neutrophil count decreased (51%), platelet count decreased (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%). Please see full U.S. Prescribing Information including U.S. Patient Information. The information provided in this press release is intended for a global audience. Product indications vary by region. About BeOne BeOne Medicines is a global oncology company domiciled in Switzerland that is discovering and developing innovative treatments that are more accessible to cancer patients worldwide. With a portfolio spanning hematology and solid tumors, BeOne is expediting development of its diverse pipeline of novel therapeutics through its internal capabilities and collaborations. With a growing global team of nearly 12,000 colleagues spanning six continents, the Company is committed to radically improving access to medicines for far more patients who need them. To learn more about BeOne, please visit www.beonemedicines.com and follow us on LinkedIn, X, Facebook and Instagram. Forward-Looking Statement This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the potential benefits of BRUKINSA and BGB-16673; and BeOne’s plans, commitments, aspirations and goals under the caption “About BeOne.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeOne’s ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeOne’s ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeOne's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeOne’s reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeOne’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products; BeOne’s ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; and those risks more fully discussed in the section entitled “Risk Factors” in BeOne’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeOne’s subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeOne undertakes no duty to update such information unless required by law. To access BeOne media resources, please visit our Newsroom. 1 National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ)–Patient Version. Accessed November 2024. https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq. 2 American Cancer Society. What is Chronic Lymphocytic Leukemia? Updated May 10, 2018. Accessed November 2024. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/what-is-cll.html. 3 American Cancer Society. Key Statistics for Chronic Lymphocytic Leukemia. Updated July 1, 2024. Accessed November 2024. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/key-statistics.html.

▎Armstrong2025年12月6-9日，美国血液学会年会（ASH）在美国佛罗里达州奥兰多举办，乐普生物CD20 ADC新药MRG001+BTK抑制剂奥布替尼联合治疗DLBCL的二期临床最新数据将在此次大会上报告。截至2025年8月31日，该II期研究共入组26例R/R DLBCL患者，所有患者均接受过至少1线标准治疗失败，80.8%的患者接受过2线及以上治疗，既往治疗线数中位数为3线（1-10线）。21例疗效可评估患者中，总缓解率（ORR）达66.7%，其中5例（23.8%）实现完全缓解（CR）、9例（42.9%）实现部分缓解（PR），疾病控制率（DCR）为85.7%。mPFS为13.1个月，mOS尚未达到。关键高危亚组疗效显著，既往接受抗CD3/CD20双特异性抗体治疗的5例患者2例达到CR、2例达到PR，1例SD，ORR为80.0%，DCR为100%；2例接受过CAR-T治疗的患者1例达到CR、1例达到PR，ORR为100.0%；7例巨块型病变患者ORR为42.9%，DCR为71.4%。安全性方面，18例（69.2%）患者出现3/4级治疗相关不良事件（TRAEs），最常见的副作用为中性粒细胞减少（76.9%），白细胞计数减少（69.2%），贫血（57.7%），血小板计数减少（53.8%），低钾血症（46.2%），淋巴细胞计数减少（38.5%）AST升高（34.6%），ALT升高（23.1%），经对症治疗后均可痊愈，无副作用导致的停药或死亡。DLBCL为最常见的非霍奇金淋巴瘤（NHL），占比约40-50%，中国2024年新发病例19万例。根据CSCO2025年指南，一线治疗以R-CHOP、Pola-R-CHP为主，有效率较高，但仍有40-50%的患者会出现难治性复发（R/R）疾病，R/R DLBCL的治疗选择包括CD3/CD20双抗、CD19单抗联合来那度胺、利妥昔单抗联合化疗等。DLBCL市场潜力巨大，且仍存在严重的未满足临床需求。罗氏CD79b ADC 2024年销售额14.63亿美元，今年前三季度销售额13.68亿美元。BTK抑制剂如伊布替尼、泽布替尼等单药治疗R/R DLBCL的疗效有限，ORR为29.3-26.8%，需要以基因分型精准选择患者（如Phoenix研究中年轻MCD/N1基因亚型）。当前BTK抑制剂在DLBCL适应症上的研究重点，已从单药探索转向与抗体偶联药物（ADC）、双特异性抗体的多维联合，通过作用机制互补，实现对肿瘤细胞的全面打击。MRG001-C002研究早期数据的读出，充分验证了这一联合治疗方案的潜力。CD3/CD20为R/R DLBCL领域的另一类重要药物，罗氏的格非妥单抗已在三线及以上R/R DLBCL适应症中获批，并同步向前线进行探索。STARGALO研究显示，格非妥单抗联合GemOx相对于R-GemOx的获益显著，中位OS（25.5个月 vs. 12.9个月；HR 0.62）、中位PFS（13.8个月 vs. 3.6个月；HR 0.40）和ORR率（68.3% vs 40.7%）更优，已在欧盟获批用于二线治疗，在美国二线治疗则因为美国入组人数少未获批准。可以看到，MRG001+BTK联合治疗取得了极具潜力的疗效数据，有望解决BTK抑制剂单药疗效不足的缺点，且相比于当前二线治疗的疗效有显著提升（非头对头）。更重要的，MRG001+BTK联合治疗对于CD3/CD20双抗耐药的4例患者仍有100%的ORR，有望为难治性R/R DLBCL患者带来更多治疗选择。总结乐普生物正在不断巩固其ADC领域的地位，前不久维贝柯妥塔单抗获批上市，成为全球首款EGFR ADC，在国际化方面，乐普生物MRG007为首款完成授权出海合作的CDH17 ADC，在胃肠道肿瘤领域的布局也进入加速发展阶段。在实体瘤ADC不断取得临床突破并进入商业化阶段的同时，血液瘤ADC也终于迎来临床突破，CD20 ADC有望为DLBCL这一血液瘤大瘤种带来全新的治疗选择，一方面与BTK抑制剂联合治疗可显著增强疗效，另一方面可以突破CD3/CD20双抗和CAR-T耐药，有望成为DLBCL领域又一款基石产品。Armstrong技术全梳理系列GPRC5D靶点全梳理；CD40靶点全梳理；CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向；Claudin 6靶点全梳理；Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇；CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理；Ambrx技术全梳理；Vir Biotech技术全梳理；Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理；Momenta技术全梳理；NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。