BeOne Medicines Presents New SEQUOIA Study Results Reinforcing BRUKINSA’s Differentiated Profile with or without Venetoclax in Frontline CLL at ASCO 2025

(BUSINESS WIRE)--BeOne Medicines Ltd. (NASDAQ: ONC; HKEX: 06160; SSE: 688235), a global oncology company, today will present new data from the Arm C and D cohorts of the pivotal, global Phase 3 SEQUOIA trial of BRUKINSA^® (zanubrutinib). The findings underscore the strong and consistent efficacy of BRUKINSA across CLL patient types, including high-risk mutation status. These data will be presented in two rapid oral presentations at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL.

Data from the Arm D of SEQUOIA demonstrate that treatment with BRUKINSA plus venetoclax has the potential to drive progression-free survival and overall deep and durable responses across the frontline CLL patient spectrum, including patients with high-risk mutational status. The best undetectable minimal residual disease (uMRD) rate in peripheral blood at a sensitivity level 10^-4 was 59%. These efficacy responses observed in Arm D, despite the high proportion of high-risk patients enrolled, are in line with recent fixed-duration studies in fitter, healthier patient populations. Additionally, 11 patients in Arm D were able to discontinue treatment early due to meeting uMRD-guided stopping criteria, and 9 patients remain in ongoing clinical remission with sustained uMRD (1 patient discontinued study while in clinical remission), allowing them to remain treatment-free. In patients without del(17p) and TP53 mutations, 43% achieved uMRD by cycle 16 and 60% by cycle 28. These data were published today in the Journal of Clinical Oncology.

“While many first-line CLL studies have excluded patient populations with high-risk disease features, BeOne included those patients in SEQUOIA,” said Lai Wang, Ph.D., Global Head of R&D at BeOne. “Nearly 88% of patients with del(17p) and /or TP53 treated with BRUKINSA plus venetoclax remain progression-free at 36 months, which represents an unprecedented outcome for a doublet regimen in this difficult-to-treat patient population. These new SEQUOIA data reinforce BRUKINSA’s versatility across the spectrum of CLL patients and reflect BeOne’s commitment to progressing a pipeline built to meet unmet patient needs and elevate the standard of care.”

Arm D Highlights (Abstract 7009)
SEQUOIA Arm D investigated BRUKINSA plus venetoclax in 114 patients with treatment-naïve (TN) CLL / small lymphocytic lymphoma (SLL) with or without del(17p) and/or TP53 high-risk mutations. At a median follow-up of 31.2 months, the combination induced a high 24-month progression-free survival (PFS) rate of 92% (95% CI, 85-96%) and an impressive overall response rate (ORR) of 97%. The 24-month overall survival (OS) rate was 96% (95% CI, 90%-98%). Of those patients with del(17p) and/or TP53 mutations, 94% were progression-free at 24 months and 87.6% were progression-free at 36 months.

The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified.

“The zanubrutinib and venetoclax combination achieved deep, durable responses across risk groups, including patients with TP53 mutations, with a generally manageable safety profile. Notably, several patients were able to discontinue treatment and maintain remission, highlighting the potential for time-limited therapy with meaningful disease control,” said Mazyar Shadman, M.D., M.P.H., Associate Professor and Innovators Network Endowed Chair, Medical Director, Cellular Immunotherapy and the Bezos Family Immunotherapy Clinic at Fred Hutch Cancer Center. “Generating data to inform future CLL treatment strategies that allow for both continuous therapy and planned time off treatment is essential, particularly for high-risk patients who are the most likely to succumb to this disease.”

Arm C Highlights (Abstract 7011)
Arm C of the SEQUOIA study investigated BRUKINSA monotherapy in patients with TN CLL / SLL and del(17p) mutations and is the largest prospective cohort of CLL/SLL patients with del(17p). At a median follow-up of over 5.5 years (65.8 months), most patients remained progression-free. Notably, at 60 months, 72.2% of patients who received BRUKINSA remained progression-free (95% CI, 62.4, 79.8). When adjusted for the impact of the COVID-19 pandemic, 73.0% of patients in the cohort remained progression-free (95% CI, 63.3, 80.6) at 60 months. The 60-month OS rate was 85.1% (95% CI, 76.9, 90.6) and 87.0% (95% CI, 79.0, 92.1) when adjusted for COVID-19. At the time of data cut-off, the ORR was 97.3%, and 62.2% of patients were still receiving treatment with BRUKINSA.

The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified.

For additional information about our presence at the 2025 ASCO Annual Meeting, 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 Approximately 20,700 new cases of CLL will be diagnosed in the U.S. in 2024.³

About 50% of CLL patients have high-risk genetic features – including del(17p), TP53 or unmutated IGHV – that may limit the effectiveness of some treatments (e.g. chemotherapy) and increase the likelihood of disease progression.^4,5

About SEQUOIA
SEQUOIA (NCT03336333) is a randomized, multicenter, global Phase 3 trial designed to evaluate the efficacy and safety of BRUKINSA in patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The trial consists of three cohorts:

• Cohort 1 (n=479): randomized 1:1 to receive BRUKINSA (n=241) or bendamustine plus rituximab (n=238) until disease progression or unacceptable toxicity, in patients not harboring del(17p); data from this group comprise the primary endpoint;
• Cohort 2/Arm C (n=110): patients with del(17p) receiving BRUKINSA as a monotherapy; and
• Cohort 3/Arm D (n=114): 66 patients with del(17p) and/or pathogenic TP53 mutation and 47 patients without del(17p) or TP53 were enrolled, with 110 patients receiving BRUKINSA in combination with venetoclax.

The results of Cohort 1 of the SEQUOIA study led to the regulatory approval of BRUKINSA monotherapy in the treatment of TN CLL in many countries across the world, including approvals by the U.S. Food and Drug Administration and the European Medicines Agency. The primary endpoint of the trial is progression-free survival (PFS), as assessed by an independent review committee (IRC). Secondary endpoints include investigator-assessed PFS, IRC- and investigator-assessed overall response rate (ORR), overall survival (OS), and safety, as well as PFS and ORR in patients with del(17p).

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. Additionally, 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 200,000 patients have been treated globally.

U.S. Indications and Important Safety Information for BRUKINSA (zanubrutinib)

INDICATIONS

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with:

• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• Waldenström’s macroglobulinemia (WM).
• Mantle cell lymphoma (MCL) who have received at least one prior therapy.
• Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen.
• Relapsed or refractory follicular lymphoma (FL), in combination with obinutuzumab, after two or more lines of systemic therapy.

The MCL, MZL and FL indications are approved under accelerated approval based on overall response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhage has occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with BRUKINSA in clinical trials, with fatalities occurring in 0.2% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 32% of patients.

Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Coadministration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days before and after surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA. Grade 3 or higher infections occurred in 26% of patients, most commonly pneumonia (7.9%), with fatal infections occurring in 3.2% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jirovecii pneumonia, and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (21%), thrombocytopenia (8%) and anemia (8%) based on laboratory measurements, developed in patients treated with BRUKINSA. Grade 4 neutropenia occurred in 10% of patients, and Grade 4 thrombocytopenia occurred in 2.5% of patients.

Monitor complete blood counts regularly during treatment and interrupt treatment, reduce the dose, or discontinue treatment as warranted. Treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 14% of patients treated with BRUKINSA. The most frequent second primary malignancy was non-melanoma skin cancers (8%), followed by other solid tumors in 7% of the patients (including melanoma in 1% of patients) and hematologic malignancies (0.7%). Advise patients to use sun protection and monitor patients for the development of second primary malignancies.

Cardiac Arrhythmias

Serious cardiac arrhythmias have occurred in patients treated with BRUKINSA. Atrial fibrillation and atrial flutter were reported in 4.4% patients treated with BRUKINSA, including Grade 3 or higher cases in 1.9% of patients. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.3% of patients.

Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort), manage appropriately, and consider the risks and benefits of continued BRUKINSA treatment.

Hepatotoxicity, Including Drug-Induced Liver Injury

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including BRUKINSA.

Evaluate bilirubin and transaminases at baseline and throughout treatment with BRUKINSA. For patients who develop abnormal liver tests after BRUKINSA, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold BRUKINSA. Upon confirmation of DILI, discontinue BRUKINSA.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for 1 week after the last dose. Advise men to avoid fathering a child during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

The most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA (N=1729) are decreased neutrophil count (51%), decreased platelet count (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with strong or moderate CYP3A inducers. Dose adjustment may be recommended with moderate CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

Please see full U.S. Prescribing Information including U.S. Patient Information.

About BeOne
BeOne Medicines is a global oncology company domiciled in Switzerland that is discovering and developing innovative treatments that are more affordable and 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 more than 11,000 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 Statements
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 BeOne’s ability to deliver advanced and effective treatments for a broad range of cancer patients; BRUKINSA’s role across CLL patients; the ability of BeOne’s pipeline to meeting evolving patient needs and elevate the standard of care; and BeOne’s plans, commitments, aspirations, and goals under the heading “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 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.

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