Mature B-Cell Neoplasm

SAN DIEGO — Some of the biggest names in BTK inhibitors presented updated datasets at the American Society of Hematology annual meeting this weekend, most notably AstraZeneca and Eli Lilly. AstraZeneca and Eli Lilly outlined how their drugs Calquence and Jaypirca can help patients with chronic lymphocytic leukemia (CLL). Individuals live with CLL chronically, unlike more aggressive cancers like acute lymphoblastic leukemia or multiple myeloma, and if they relapse often have other effective drugs to turn to. In addition, BeiGene reported five-year follow-up data for its drug Brukinsa in first-line CLL. Mehrdad Mobasher, BeiGene’s chief medical officer in hematology, said the follow-up is “one of the most important” updates for Brukinsa at the medical meeting, as it shows sustained efficacy following the drug’s approval in CLL last January. AstraZeneca this weekend expanded on its Phase 3 win from July for fixed-dose Calquence regimens in first-line CLL, combining the drug with AbbVie and Roche’s Venclexta, with or without Roche’s Gazyva. Researchers tested the regimens in 867 patients, randomizing them 1-to-1-to-1 against Rituxan plus chemo. Both regimens met the primary endpoint of progression-free survival, with the triple regimen of Calquence, Venclexta and Gazyva lowering patients’ risk of disease progression or death by 58% and achieving a progression-free survival (PFS) rate of 83.1% after 36 months of treatment. The Calquence and Venclexta combo reported a PFS of 76.5%, reducing disease progression or death by 35%, and the control group achieved a 65.5% PFS rate. Both results were statistically significant. AstraZeneca also conducted analyses that excluded deaths in the trial that were a result of Covid-19, since the company was enrolling patients during the height of the pandemic. When those deaths were excluded, the triple regimen reduced patients’ risk of disease progression or death by 74%, and the double regimen by 29%. Susan Galbraith, AstraZeneca’s EVP of oncology R&D, declined to comment on the company’s regulatory plans. But she told Endpoints News that she doesn’t believe it will be difficult to market the drug since patients and physicians are already familiar with all three therapies. “We have it established with both community oncologists, as well as physicians who are in academic centers,” Galbraith said. “I don’t think it will be difficult to drive uptake of this.” Galbraith added she thinks it will be mostly new CLL patients who end up taking the regimens, rather than those who have been taking Calquence already without Venclexta. Calquence is currently approved in CLL as a monotherapy and in combination with Gazyva. Eli Lilly’s third-generation BTK inhibitor Jaypirca bested investigators’ choice treatments in previously treated CLL and small lymphocytic leukemia (SLL), meeting the primary endpoint in a confirmatory trial. In the Phase 3 BRUIN CLL-321 study, Jaypirca reduced patients’ risk of relapse, disease or death by 46% compared to two regimens consisting of either idelalisib plus rituximab or bendamustine plus rituximab. The drug won accelerated approval last December in patients who’ve been treated with at least two prior therapies, including one other BTK inhibitor and a BCL-2 inhibitor. Lilly Oncology president Jacob Van Naarden said the company will file with the FDA for full approval “soon.” “We almost doubled the progression-free survival in the clinical trial,” chief medical officer David Hyman told Endpoints . At a median follow-up of 19 months, median progression-free survival in the Jaypirca arm was 14 months compared with 8.7 months in the control arm, as assessed by an independent review committee. Van Naarden said this was the first randomized Phase 3 CLL trial in patients who previously received a BTK inhibitor. The results, he said, could potentially make the case for Jaypirca’s use in earlier settings. “In real clinical practice, most patients start with a covalent BTK inhibitor, they eventually relapse. They get a venetoclax-based regimen, they eventually relapse, and then they’re getting pirtobrutinib,” Van Naarden said ahead of Lilly’s data release. “The data we’re presenting tomorrow raise the question of whether or not pirto should be used before venetoclax in certain patients or not.” While there wasn’t a statistically significant difference between the Jaypirca and control arms in overall survival, Van Naarden and Hyman said the data were confounded by high degrees of crossover. Patients in the control arm were allowed to switch to Jaypirca after seeing disease progression, and a majority of them (76%) did. Lilly reported that multiple analyses adjusting for the crossover effect showed trends in favor of Jaypirca. “We never, ever powered or contemplated this study to be designed to demonstrate a survival benefit,” Hyman said. “In CLL, basically all of the things that we do are based on progression-free survival.” BeiGene touted a “deepening of responses” in five-year follow-up data for its BTK inhibitor Brukinsa in CLL or SLL. At a median follow-up of 61.2 months, Brukinsa reduced first-line patients’ risk of disease progression or death by 71% compared to a combination of the cancer drugs bendamustine and Rituxan, BeiGene said at ASH. The results are from the Phase 3 SEQUOIA study, which helped support Brukinsa’s approval in CLL last year. “Efficacy is sustained. Responses are getting deeper,” BeiGene’s Mobasher told Endpoints. “Brukinsa has now proven to be the best-in-class BTK inhibitor.” BeiGene is also studying Brukinsa in combination with its experimental BCL2 inhibitor sonrotoclax. The company reported updated Phase 1/1b results at this year’s ASH suggesting the combination was well-tolerated and achieved a 99% overall response rate in patients with mature B-cell malignancies at a median follow-up of 19.4 months. The Brukinsa sonrotoclax combination is currently in an ongoing fixed-duration Phase 3 study, which started last year and is “enrolling extremely well,” Mobasher said.

SAN MATEO, Calif.--( BUSINESS WIRE )--BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to BGB-16673, an orally available investigational Bruton’s tyrosine kinase (BTK) targeting chimeric degradation activation compound (CDAC), for adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have been previously treated with at least two prior lines of therapy, including BTK inhibitor (BTKi) and B-cell lymphoma 2 (BCL2) inhibitor. The FDA’s Fast track designation is aimed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to patients earlier. “When disease progression for patients on BTK inhibitors occurs, there is a need for BTK-targeting agents with a different mode of action given the centrality of this pathway in CLL/SLL. BTK-protein degradation with our BTK CDAC (BGB-16673) may address this unmet need,” said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology. “The FDA’s Fast Track Designation supports our goal of efficiently developing BGB-16673 for these patients, the first investigational drug from our CDAC platform. We believe BGB-16673 strengthens our hematology leadership and complements BRUKINSA (zanubrutinib), the backbone for our investigational hematology pipeline. BGB-16673 is the most advanced BTK degrader in the clinic and is well-suited to become an important therapy for patients progressing after BTKi who have limited options.” The designation was requested based on the potential for BGB-16673 to address an unmet medical need for patients CLL/SLL whose disease has progressed. Data from ongoing first-in-human Phase 1/2 ( NCT05006716 ) presented at the European Hematology Association 2024 Hybrid Congress in June highlighted the tolerable safety and promising efficacy in heavily pretreated patients with R/R CLL/SLL. More than 300 patients have been treated to date in 15 countries across the BGB-16673 global clinical development program. About Chronic Lymphocytic Leukemia A life-threatening cancer of adults, chronic lymphocytic leukemia (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. 1,2 CLL is the most common type of leukemia in adults, accounting for about one-third of new cases of leukemia. 2,3 Approximately 20,700 new cases of CLL will be diagnosed in the U.S. in 2024. 3 About BGB-16673 BGB-16673 is an orally available Bruton’s tyrosine kinase (BTK) targeting chimeric degradation activation compound (CDAC) designed to induce degradation of wildtype and multiple mutant forms of BTK, including those that commonly confer resistance to BTK inhibitors in patients who experience progressive disease. About BeiGene BeiGene is a global oncology company that is discovering and developing innovative 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. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn , X (formerly known as Twitter), 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 the ability of BGB-16673 to fulfill an unmet medical need; BeiGene’s ability to efficiently develop BGB-16673; whether BGB-16673 becomes an important therapy for patients progressing after BTKi who have limited options; 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; BeiGene’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 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. To access BeiGene media resources, please visit our News & Media site. 1 National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ)–Patient Version. Accessed November 2023. 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 2023. 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 August 2024. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/key-statistics.html .

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)-- 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 pro 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 pro 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 pro 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 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 pro 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. . ii American Cancer Society. What is Chronic Lymphocytic Leukemia? Updated May 10, 2018. Accessed November 2023. . iii American Cancer Society. Key Statistics for Chronic Lymphocytic Leukemia. Updated January 12, 2023. Accessed November 2023. .