On May 14, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported it will share new data from its hematology portfolio and pipeline at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress (EHA2024) in Madrid, Spain, June 13-16, 2024 (Press release, BeiGene, MAY 14, 2024, View Source [SID1234643210]). BeiGene has 28 abstracts accepted at EHA (Free EHA Whitepaper)2024, with four scheduled for oral presentations.
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"As part of our dedication to bringing high-quality therapies to patients around the world, our presentations at EHA (Free EHA Whitepaper)2024 underscore our continued commitment to expanding our hematology portfolio and our efforts to build on the success of BRUKINSA’s unique clinical profile across multiple B-cell malignancies," said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. "The data highlight the potential of our differentiated investigational BCL2 inhibitor, sonrotoclax, as a monotherapy and in combination regimens, and the promise of BTK degradation to address the unmet needs of patients facing certain blood cancers."
New Data Expand Evidence Base for BRUKINSA (zanubrutinib)
Oral presentation of new data from an arm of the SEQUOIA study in patients with high-risk treatment-naïve (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with del(17p) and/or TP53 mutation treated with BRUKINSA and venetoclax, demonstrating strong efficacy and favorable safety (Abstract S160)
Oral presentation sharing the results of an adverse event (AE) based economic analysis comparing BRUKINSA with acalabrutinib; in terms of AE management, BRUKINSA was cost-saving and associated with quality of life benefits compared to acalabrutinib (Abstract S333)
Presentation of a post hoc analysis evaluating the risk of developing hypertension among ALPINE trial participants with relapsed or refractory (R/R) CLL/SLL, which demonstrated patients in the ibrutinib arm initiated new and/or a new class of anti-hypertensive medications more frequently than patients in the BRUKINSA arm (Abstract P1836)
Results of an intra-patient comparative analysis from ROSEWOOD study of BRUKINSA plus obinutuzumab in patients with R/R follicular lymphoma (FL), supporting the efficacy benefit of the combination in this patient population (Abstract P1143)
Multiple additional presentations featuring patient-reported outcomes and real-world differentiation of BRUKINSA among BTK inhibitors
Emerging Data Demonstrate Hematology Pipeline Strengths
Oral presentation of a Phase 1 study of BeiGene’s novel BCL2 inhibitor sonrotoclax (BGB-11417) in combination with BRUKINSA, demonstrating deep and durable responses with a tolerable safety profile in patients with R/R CLL/SLL; the combination of sonrotoclax with backbone therapy BRUKINSA is being evaluated in the randomized Phase 3 CELESTIAL study (NCT06073821) in patients with TN CLL (Abstract S156)
Poster presentation of Phase 1a/1b open-label dose escalation and expansion study of sonrotoclax in combination with BRUKINSA in R/R mantle cell lymphoma (MCL), showing the combination was generally well tolerated and demonstrated promising efficacy, including high rate of deep and durable responses (Abstract P1112)
Additional presentations highlighting Phase 1 results for sonrotoclax, demonstrating encouraging response rates, durable responses and manageable safety profiles spanning multiple indications across B-cell and myeloid malignancies, including:
As monotherapy in R/R Waldenström’s macroglobulinemia (Abstract P1110)
In combination with azacitidine in both TN and R/R acute myeloid leukemia (Abstracts P538 and P562)
In combination with dexamethasone in R/R multiple myeloma harboring t(11;14) (Abstract P898)
Oral presentation of data from the ongoing, first-in-human Phase 1/2 study of BeiGene’s Bruton tyrosine kinase (BTK) degrader BGB-16673, highlighting tolerable safety and promising efficacy in heavily pretreated patients with R/R CLL/SLL (NCT05006716); BGB-16673, which induces BTK degradation, is the first investigational drug from BeiGene’s chimeric degradation activation compound (CDAC) platform (Abstract S157)
Additional data from the Phase 1/2 study of BTK CDAC BGB-16673, demonstrating a tolerable safety profile and preliminary efficacy in heavily pretreated patients with different types of non-Hodgkin lymphoma, including those with BTKi-resistant disease (Abstract P1119)
BeiGene Presentations During EHA (Free EHA Whitepaper)2024
Abstract Title
Abstract #
Presentation Type
Presenting Author
BTK CDAC (investigational compound)
Preliminary efficacy and safety of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients with relapsed or refractory (R/R) CLL/SLL: Results from the phase 1 BGB-16673-101 study
S157
Oral
R. Parrondo
Preliminary efficacy and safety of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients with relapsed or refractory (R/R) indolent NHL: Results from the phase 1 BGB-16673-101 study
P1119
Poster
C. Cheah
Sonrotoclax (investigational compound)
Results from the phase 1 study of the novel BCL2 inhibitor sonrotoclax (sonro) in combination with zanubrutinib (zanu) for relapsed/refractory (R/R) CLL/SLL show deep and durable responses
S156
Oral
S. Opat
Combination treatment with novel BCL-2 inhibitor sonrotoclax (BGB-11417) and zanubrutinib induces high rate of complete remission for patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL)
P1112
Poster
C. Tam
Safety and efficacy results of a phase 1 study of the novel BCL2 inhibitor sonrotoclax (BGB-11417) for relapsed/refractory Waldenström’s macroglobulinemia
P1110
Poster
C Cheah
Preliminary safety and antileukemic activity of sonrotoclax (BGB-11417), a potent and selective BCL2 inhibitor, in treatment-naive patients with acute myeloid leukemia
P538
Poster
S. Tan
Preliminary safety and antileukemic activity of sonrotoclax (BGB-11417), a potent and selective BCL2 inhibitor, in patients with relapsed/refractory acute myeloid leukemia
P562
Poster
P. Montesinos
Sonrotoclax plus dexamethasone is tolerable and demonstrates antimyeloma activity in patients with relapsed/refractory (R/R) multiple myeloma harboring t(11;14)
P898
Poster
B. Dhakal
BGB-11417-203, an ongoing, phase 2 study of sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, in patients with Waldenström macroglobulinemia
PB2954
Online abstract
J. Matous
CELESTIAL-TN CLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naive (TN) CLL
PB2540
Online abstract
P. Patten
Zanubrutinib
Combination of zanubrutinib + venetoclax for treatment-naive (TN) CLL/SLL with del(17p) and/or TP53: Preliminary results from SEQUOIA arm D
S160
Oral
P. Ghia
Intra-patient comparative analysis of zanubrutinib plus obinutuzumab efficacy in relapsed/refractory follicular lymphoma using the Growth Modulation Index
P1143
Poster
K. Bouabdallah
Risk of hypertension in patients with CLL/SLL who participated in ALPINE: A post hoc analysis
P1836
ePoster
W. White
Risk of new-onset hypertension in newly diagnosed chronic lymphocytic leukemia patients treated with Bruton tyrosine kinase inhibitors: A real-world study using the Symphony Health Solutions database
P1847
ePoster
W. White
Zanubrutinib vs. acalabrutinib in B-cell malignancies: an adverse event-based economic analysis
S333
Oral
T. Munir
Efficacy of zanubrutinib versus acalabrutinib in the treatment of relapsed or refractory chronic lymphocytic leukemia (R/R CLL): A matching-adjusted indirect comparison (MAIC)
P700
Poster
M. Shadman
Efficacy and safety of zanubrutinib vs. venetoclax+ibrutinib in the treatment-naïve (TN) chronic lymphocytic leukemia (CLL): A matching-adjusted indirect comparison (MAIC)
P702
Poster
T. Munir
Matching-adjusted indirect comparison (MAIC) of zanubrutinib versus real-world chemoimmunotherapy (CIT) or chemotherapy (chemo) in relapsed/refractory marginal zone lymphoma (R/R MZL)
P1123
Poster
R. Walewska
Indirect comparison of efficacy of zanubrutinib versus acalabrutinib in the treatment of relapsed/refractory mantle cell lymphoma
P2058
ePoster
B. Shah
Comparative efficacy of Bruton tyrosine kinase inhibitors in the treatment of relapsed/refractory chronic lymphocytic leukemia: A network meta-analysis
P701
Poster
M. Shadman
Zanubrutinib vs other Bruton’s tyrosine kinase inhibitors in relapsed/refractory chronic lymphocytic leukemia: A multilevel network meta-regression
P698
Poster
M. Shadman
Patient-reported outcome (PRO)–based recurrent symptomatic deterioration predicts disease progression: Results from the ALPINE trial
P1834
ePoster
J. Brown
Real-world comparative effectiveness of covalent Bruton tyrosine kinase inhibitors (cBTKi) among patients with relapsed/refractory mantle cell lymphoma (R/R MCL)
P1139
Poster
T. Phillips
Real-world treatment switching and sequencing to next line of therapy of zanubrutinib, acalabrutinib, and ibrutinib in CLL/SLL
P697
Poster
J. Pinilla-Ibarz
Real-world Bruton tyrosine kinase inhibitor treatment patterns and outcomes among patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in US community oncology practices
P685
Poster
J. Hou
Real-world evaluation of treatment pattern, time to next treatment, healthcare resource utilization, and cost of care in follicular lymphoma
P1124
Poster
S. Gaballa
Real-world adherence and healthcare resource utilization of Bruton tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma
P2045
ePoster
B. Shah
Recent patterns of care with BTK inhibitors and distribution of social determinants of health among patients with CLL/SLL in the US community setting
PB2546
Online abstract
D. Andorsky
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.
About Sonrotoclax (BGB-11417)
Sonrotoclax is an investigational small molecule B-cell lymphoma 2 (BCL2) inhibitor. It belongs to a class of BCL2 homology 3 (BH3) mimetics, and preclinical and IND-enabling studies have demonstrated potent activity and high selectivity of sonrotoclax against the antiapoptotic protein BCL2. Sonrotoclax is more potent and selective for BCL2 relative to BCLxL than venetoclax and shows the potential to overcome common BCL2 resistance mutations.
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.
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.
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.
This information is intended for a global audience. Product indications vary by region.