FDA Approves Label Update for BRUKINSA® (zanubrutinib) in Chronic Lymphocytic Leukemia (CLL)

U.S. label update includes superior progression-free survival results from the Phase 3 ALPINE head-to-head trial of BRUKINSA versus IMBRUVICA^® (ibrutinib) in Relapsed or Refractory CLL

ALPINE is the only Phase 3 Bruton’s tyrosine kinase (BTK) inhibitor trial to demonstrate superiority versus IMBRUVICA

BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.–(BUSINESS WIRE)–$BGNE #BeiGene–BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, today announced the U.S. Food and Drug Administration (FDA) has approved a label update for BRUKINSA^® (zanubrutinib) to include superior progression-free survival (PFS) results from the Phase 3 ALPINE trial comparing BRUKINSA against IMBRUVICA^® (ibrutinib) in previously treated patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL).

“The ALPINE trial is the first and only study to demonstrate PFS superiority in a head-to-head comparison versus ibrutinib in CLL,” said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. “BRUKINSA was approved in the U.S. for CLL at the beginning of 2023, and we submitted additional data from the ALPINE PFS analysis supporting it as the BTK inhibitor of choice in CLL, solidifying it as an important treatment option for patients. When making treatment decisions, it is critical that physicians and patients understand the totality of data supporting BRUKINSA’s robust efficacy and differentiated safety in CLL.”

The updated label is based on a prespecified analysis of the ALPINE trial, which demonstrated superior efficacy and a favorable cardiac safety profile for BRUKINSA versus ibrutinib in patients with R/R CLL and was presented in a late-breaking session at the 64th Annual American Society for Hematology (ASH) Meeting and Exposition and published simultaneously in The New England Journal of Medicine. The updated label includes data at a median follow-up of 31 months, in which BRUKINSA demonstrated superior PFS compared with ibrutinib in patients with R/R CLL (HR: 0.65 [95% CI, 0.49-0.86] P=.0024, for both investigator and independent review committee). Additionally, BRUKINSA demonstrated a favorable cardiac safety profile with significantly lower rates of atrial fibrillation/flutter (5.2% vs. 13.3%) and zero deaths due to cardiac disorders with BRUKINSA versus six with ibrutinib (0% vs. 1.9%).

Please see Important Safety Information below.

At the recent 65th Annual ASH Meeting and Exposition, BeiGene presented extended follow-up data from the ALPINE trial at a median follow-up of 39 months. The data demonstrate that BRUKINSA continues to show sustained PFS benefit versus ibrutinib (HR: 0.68 [95% CI, 0.53-0.86] P=0.0011) among R/R CLL patients receiving more than three years of treatment, with durable PFS benefits observed across subgroups, including patients with 17p deletion or TP53 mutation (HR: 0.52 [95% CI, 0.33-0.83] P=0.0047). PFS benefit is consistent across multiple sensitivity analyses, demonstrating that PFS advantage with BRUKINSA was primarily driven by efficacy and not tolerability. The overall safety and tolerability profile was consistent with previous ALPINE analyses, including persistently lower rates of cardiovascular events reported with BRUKINSA. The most commonly reported treatment emergent adverse events (≥20%) with BRUKINSA were COVID-19-related, neutropenia, hypertension, and upper respiratory tract infection.

BRUKINSA is approved in more than 65 countries, including the U.S., China, EU, Great Britain, Canada, Australia, South Korea, and Switzerland, in selected indications and under development for additional indications globally. In the U.S., BRUKINSA is approved for the treatment of adult patients with CLL or small lymphocytic lymphoma, Waldenström’s macroglobulinemia, mantle cell lymphoma who have received at least one prior therapy, and relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20-based regimen. The global BRUKINSA development program includes more than 5,000 subjects enrolled to date in 29 countries and regions.

About Chronic Lymphocytic Leukemia (CLL)

A life-threatening cancer of adults, CLL 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.^i,ii CLL is the most common type of leukemia in adults, accounting for about one-quarter of new cases of leukemia.^ii,iii Approximately 18,740 new cases of CLL will be diagnosed in the United States in 2023.ⁱⁱⁱ

About BRUKINSA^® (zanubrutinib)

BRUKINSA is a 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.

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

The MCL and MZL indications are approved under accelerated approval based on overall response rate. 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 monotherapy. Grade 3 or higher hemorrhage, including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 3.6% of patients treated with BRUKINSA monotherapy in clinical trials, with fatalities occurring in 0.3% of patients. Bleeding of any grade, excluding purpura and petechiae, occurred in 30% 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 pre- and post-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 monotherapy. Grade 3 or higher infections occurred in 24% of patients, most commonly pneumonia (11%), with fatal infections occurring in 2.9% of patients. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci 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 (22%), thrombocytopenia (8%) and anemia (7%) based on laboratory measurements, developed in patients treated with BRUKINSA monotherapy. Grade 4 neutropenia occurred in 11% of patients, and Grade 4 thrombocytopenia occurred in 2.8% 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 13% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was non-melanoma skin cancer reported in 7% of patients. Other second primary malignancies included malignant solid tumors (5%), melanoma (1.2%), and hematologic malignancies (0.5%). 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 3.7% of 1550 patients treated with BRUKINSA monotherapy, including Grade 3 or higher cases in 1.7% 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 0.2% 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.

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

In this pooled safety population, the most common adverse reactions, including laboratory abnormalities, in ≥30% of patients who received BRUKINSA (N=1550) included decreased neutrophil count (42%), upper respiratory tract infection (39%), decreased platelet count (34%), hemorrhage (30%), and musculoskeletal pain (30%).

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 and U.S. Patient Information.

About BeiGene

BeiGene is a global biotechnology company that is discovering and developing innovative oncology treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn and X (formerly known as Twitter).

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 whether BRUKINSA is the BTK inhibitor of choice in CLL and its importance as a treatment option for patients; the efficacy and safety profile of BRUKINSA for patients with CLL; and BeiGene’s plans, commitments, aspirations, and goals under the heading “About BeiGene.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene’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; BeiGene’s ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene’s ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene’s reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its 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 BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene’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 BeiGene undertakes no duty to update such information unless required by law.

IMBRUVICA^® is a registered trademark of Pharmacyclics LLC and Janssen Biotech, Inc.

i National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ)–Patient Version. Accessed November 2023. https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq.

ii American Cancer Society. What is Chronic Lymphocytic Leukemia? Updated May 10, 2018. Accessed November 2023. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/what-is-cll.html.

iii American Cancer Society. Key Statistics for Chronic Lymphocytic Leukemia. Updated January 12, 2023. Accessed November 2023. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/key-statistics.html.

 

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