Sonrotoclax

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 it will share new data across a range of B-cell malignancies and assets, including best-in-class Bruton’s tyrosine kinase (BTK) inhibitor BRUKINSA ® (zanubrutinib), at the 66 th ASH Annual Meeting and Exposition in San Diego, December 7-10. BeiGene has 21 abstracts accepted at ASH 2024, with four selected for oral presentation. “In the five years since its initial approval, BRUKINSA has become a standard of care for patients facing many B-cell malignancies, and our data featured at ASH demonstrated how long-term follow-up of treatment with BRUKINSA elicited deep and durable responses, including in patients with chronic lymphocytic leukemia and Waldenström’s macroglobulinemia,” said Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. “BRUKINSA is just the starting point – pipeline data for our BTK degrader BGB-16673 and BCL2 inhibitor sonrotoclax showcase our continued leadership across the hematology landscape and our commitment to bringing innovative medicines to as many people with cancer as possible.” Presentations Highlight Sustained Progression-Free Survival and Deepening Durable Responses for Patients Treated with BRUKINSA in Treatment-Naïve and Relapsed/Refractory (R/R) Settings Five-year follow-up results from Cohort 1 of the Phase 3 SEQUOIA study showed sustained progression-free survival (PFS) benefit with BRUKINSA in patients with treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), with no new safety signals observed. Results from the LTE (long-term extension rollover) study of patients with treatment-naïve and R/R CLL also showed that treatment with BRUKINSA as a single agent or as an investigational treatment in combination with obinutuzumab achieved high overall and complete response rates. With a median follow-up of up to 6.5 years, the responses were sustained, and no new safety signals were observed. Results from an LTE study of patients with Waldenström macroglobulinemia (WM) from the Phase 3 ASPEN study, with a median follow-up of up to 5.8 years, demonstrated that treatment with BRUKINSA monotherapy remained durable and the safety/tolerability profile remained favorable. Data from a Phase 2 study showed patients with prior intolerance to acalabrutinib were able to safely and effectively switch to BRUKINSA, with the majority of patients not experiencing recurrence of prior acalabrutinib-intolerance events while maintaining or deepening responses. Pipeline Data Show Early Safety and Efficacy Across Multiple B-cell Malignancies First-in-human Phase 1/2 CaDAnCe-101 presentations (two oral, one poster) highlighted generally manageable safety and promising efficacy results for BTK degrader, BGB-16673, in patients with R/R CLL/SLL, WM, and R/R indolent non-Hodgkin’s lymphoma. BGB-16673, which induces BTK degradation, is the first and most advanced asset from BeiGene’s chimeric degradation activation compound (CDAC) platform. Oral presentation of the BGB-11417-101 Phase 1 study demonstrated B-cell lymphoma 2 (BCL2) inhibitor sonrotoclax in combination with BRUKINSA continued to show promising efficacy and was generally well-tolerated in patients with treatment-naïve CLL/SLL; this combination is being evaluated in the Phase 3 CELESTIAL-TNCLL study ( NCT06073821 ). BeiGene Presentations During ASH 2024 Abstract Title Presentation Details Lead Author BRUKINSA Prospective patient preference study for Bruton tyrosine kinase inhibitor (BTKi) treatment attributes and factors affecting patient shared decision-making CLL/SLL in the USA Publication #2265 Poster Dec. 7, 5:30-7:30 p.m. S. Ailawadhi Real-world Bruton tyrosine kinase inhibitor (BTKi) utilization and clinical outcomes among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) Publication #2353 Poster Dec. 7, 5:30-7:30 p.m. J. Hou Long-term clinical outcomes in patients with Waldenström macroglobulinemia (WM) who received zanubrutinib in the phase 3 ASPEN study: A report from the zanubrutinib extension study Publication #3031 Poster Dec. 8, 6-8 p.m. S. D’Sa Patient medication preferences in follicular lymphoma (FL) in the United States (USA): A discrete choice experiment (DCE) Publication #3655 Poster Dec. 8, 6-8 p.m. S. Gaballa Evaluating reasons for differences in real-world (RW) clinical outcomes among patients with R/R MCL on covalent BTKis Publication #3732 Poster Dec. 8, 6-8 p.m. T. Phillips Sustained superiority of zanubrutinib vs bendamustine + rituximab in treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma (TN CLL): 5-year follow-up of cohort 1 from the SEQUOIA study Publication #3249 Poster Dec. 8, 6-8 p.m. M. Shadman Deep and sustained responses in patients with CLL treated with zanubrutinib or zanubrutinib + obinutuzumab in phase 1/2 AU-003 and phase 1b GA-101 studies: A report from the zanubrutinib extension study Publication #3255 Poster Dec. 8, 6-8 p.m. C. Tam Comparative efficacy of zanubrutinib plus obinutuzumab versus last prior treatment in relapsed/refractory follicular lymphoma: Growth modulation index analysis from ROSEWOOD study Publication #3029 Poster Dec. 8, 6-8 p.m. J. Trotman Impact of novel therapies (NTs) on real-world (RW) clinical outcomes of patients (pts) with relapsed/refractory (R/R) mantle-cell lymphoma (MCL) by race/ethnicity and TP53 mutation status Publication #5097 Poster Dec. 9, 6-8 p.m. T. Phillips Zanubrutinib is well tolerated and effective in acalabrutinib-intolerant patients with B-cell malignancies Publication #4632 Poster Dec. 9, 6-8 p.m. M. Shadman Long-term impact of dose interruptions (DIs) of Bruton tyrosine kinase inhibitors (BTKis) on change in IgM levels and clinical outcomes in Waldenström macroglobulinemia (WM) Publication #4412 Poster Dec. 9, 6-8 p.m. J. Trotman Final analysis of a phase 1 study of zanubrutinib plus lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma Publication #986 Oral Dec. 9, 4:45 p.m. Z. Song Treatment with zanubrutinib in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who were previously treated with another Bruton tyrosine kinase inhibitor in a US community oncology setting Publication #7763 Online D. Andorsky BGB-16673 (BTK CDAC) Preliminary efficacy and safety of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed or refractory (R/R) indolent NHL: Results from the phase 1 CaDAnCe-101 study Publication #1649 Poster Dec. 7, 5:30-7:30 p.m. C. Tam Preliminary efficacy and safety of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed or refractory Waldenström macroglobulinemia: Results from the phase 1 CaDAnCe-101 study Publication #860 Oral Dec. 9, 3 p.m. J. Seymour Preliminary efficacy and safety of the Bruton tyrosine kinase degrader BGB-16673 in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Results from the phase 1 CaDAnCe-101 study Publication #885 Oral Dec. 9, 3:15 p.m. M. Thompson BGB-16673, a selective BTK degrader, exhibits deeper inhibition of cancer cell signaling pathways and better efficacy in MCL models Publication #5833 Online H. Wang Sonrotoclax (BCL2 Inhibitor) Sonrotoclax and zanubrutinib as frontline treatment for CLL demonstrates high MRD clearance rates with good tolerability: Data from an ongoing phase 1/1b study BGB-11417-101 Publication #1012 Oral Dec. 9, 5:15 p.m. J. Soumerai CELESTIAL-TNCLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naive CLL Publication #6807 Online P. Patten BGB-11417-203, an ongoing, phase 2 study of sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, in patients with Waldenström macroglobulinemia Publication #6289 Online H. Lee Cell Therapy Research iPSC-derived CAR-γδT with SOCS1/CISH/BIM/FAS combinatorial KO demonstrated extended longevity and profound anti-tumor efficacy without cytokine support in preclinical studies Publication #4790 Poster Dec. 7, 5:30-7:30 p.m. J. Yu Select Investigator-Initiated Trial Multicenter Phase II trial of zanubrutinib, obinutuzumab, and venetoclax (BOVen) in treatment-naïve chronic lymphocytic leukemia: 5-year follow up, retreatment outcomes, and impact of MRD kinetics (ΔMRD400) Publication #1867 Poster Dec. 7, 5:30-7:30 p.m. J. Soumerai 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. The global BRUKINSA clinical development program includes about 6,000 patients enrolled in 30 countries and regions across more than 35 trials. BRUKINSA is approved in more than 70 markets, and more than 100,000 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 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 BeiGene’s continued leadership in hematology and commitment to bringing innovative medicines to as many people with cancer as possible; the safety and efficacy of BeiGene’s pipeline assets; 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.