Bendamustine Hydrochloride

New network meta-analysis demonstrates favorable progression-free survival for patients treated with BRUKINSA vs other BTKi's Analysis of Kaiser Permanente database shows BRUKINSA effective and generally well tolerated, including in patients switching to BRUKINSA from ibrutinib ALPINE post hoc analysis shows less frequent initiation of new antihypertensives or a new class of antihypertensives in patients treated with BRUKINSA vs. ibrutinib SAN MATEO, Calif.--(BUSINESS WIRE)-- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, today announced the presentation of new analyses for BRUKINSA® (zanubrutinib) at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, May 31 - June 4, 2024. The presentations highlight analyses of the efficacy and safety of BRUKINSA compared to other Bruton’s tyrosine kinase inhibitors (BTKis) used to treat chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). “At this year’s ASCO, multiple presentations continue to add to our extensive body of evidence demonstrating BRUKINSA’s uniquely differentiated clinical profile,” Mehrdad Mobasher, M.D., M.P.H., Chief Medical Officer, Hematology at BeiGene. “These new analyses, which highlight improved PFS and response rates and a low usage of antihypertensive medicines, provide valuable insights for oncologists to consider when making treatment decisions for their patients with CLL and SLL.” BRUKINSA Survival and Response Rates for CLL vs. Acalabrutinib and other BTKis in a Network Meta-Analysis A network meta-analysis evaluated the relative efficacy of available treatments for patients with high-risk relapsed/refractory (R/R) CLL using data from three randomized controlled clinical trials: ALPINE, ELEVATE-RR and ASCEND. The analysis found a statistically significant improvement in PFS for BRUKINSA over acalabrutinib in high-risk patients and a trend toward improvement in overall survival (OS), overall response (ORR) and complete response (CR). BRUKINSA led to statistically significant improvements in PFS, as well as a trend toward improvement in OS, vs. ibrutinib and bendamustine + rituximab/idelalisib + rituximab (BR/IR). “Given the lack of head-to-head trials comparing BTK inhibitors in high-risk R/R CLL patients, we undertook a network meta-analysis to estimate the relative efficacy of available treatments,” said Mazyar Shadman, M.D. M.P.H, Associate Professor and Innovators Network Endowed Chair, Assistant Medical Director, Cellular Immunotherapy, Fred Hutch Cancer Center and University of Washington. “We found zanubrutinib to be the most efficacious BTKi for patients with high-risk R/R CLL, offering significantly delayed disease progression and favorable response compared with the other BTKi treatments in the analysis, including acalabrutinib.” Network meta-analyses are intended to be hypothesis-generating, and do not establish superior efficacy or safety of one drug over another. Results should be viewed in the context of analysis limitations and available randomized clinical trial data. This poster will be presented Monday, June 3, from 9 a.m. – noon CT (Abstract #7048). BRUKINSA Effective and Generally Well-Tolerated for Patients with CLL/SLL Regardless of Prior Ibrutinib Use A retrospective analysis assessed treatment patterns, treatment-emergent adverse events (TEAEs), treatment-limiting adverse events (TLAEs) and treatment-related mortality among patients with CLL/SLL treated at Kaiser Permanente Northern California. Among 281 patients who received BRUKINSA, 190 switched from ibrutinib and 91 received only BRUKINSA, with a median follow up of 24.4 and 8.2 months, respectively. Similar TEAE rates were seen with both BTKi therapies, with lower TLAE rates with BRUKINSA. Cardiac TLAE and non-TLAE rates overall were higher with ibrutinib than BRUKINSA, and the rates decreased after switching to BRUKINSA. There were no reports of treatment-related deaths. This poster will be presented Monday, June 3, from 9 a.m. – noon CT (Abstract #11158). ALPINE Post Hoc Analysis Shows Less Frequent Initiation of Anti-hypertensive Medications in Patients Treated with BRUKINSA vs. Ibrutinib A post-hoc analysis of the ALPINE clinical trial data evaluated the risk of developing hypertension based on initiation of anti-hypertensive medications among patients with CLL/SLL treated with BRUKINSA vs. ibrutinib. The analysis found that initiation of new anti-hypertensives or a new class of anti-hypertensives occurred less frequently in the BRUKINSA arm vs. the ibrutinib arm. In addition, initiation of anti-hypertensives occurred sooner for patients treated with ibrutinib vs. BRUKINSA. Data from this analysis provide important insights when evaluating the overall safety pro individual BTKi treatments. This abstract is available online (Abstract #e19016). During the meeting, BeiGene will also sponsor a virtual panel discussion featuring perspectives from leading hematology/oncology experts as they discuss the BTKi treatment evolution, and the considerations healthcare providers and patients should weigh when choosing treatment for CLL. The panel, titled “Exploring the landscape of next-generation BTK inhibitors in blood cancers” will take place during the Endpoints at #ASCO24 event on June 4 at 12:35 – 1:05 p.m. ET (register here). For additional information about BeiGene’s presence at the 2024 ASCO Annual Meeting, please visit our meeting hub in our newsroom. 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. 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. 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 and follow us on LinkedIn, X (formerly known as Twitter), and Facebook. 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 BRUKINSA’s differentiated clinical profile; the efficacy of zanubrutinib for patients with high-risk R/R CLL compared to other BTKi treatments; 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. View source version on businesswire.com: Contacts Investor: Liza Heapes +1 857-302-5663 ir@beigene.com Media: Kyle Blankenship +1 667-351-5176 media@beigene.com Source: BeiGene, Ltd. View this news release online at:

Pictured: A graphic showing figures on opposing coin stacks/Taylor Tieden for BioSpace Last year, empowered by new SEC reporting guidelines, BioSpace released its inaugural annual CEO pay gap report, looking at how much more top biopharma executives earned than their employees in 2022. Results showed that many biopharma executives earn more than 200 times what the company’s median employee makes. Looking at 2023 data, we found that little has changed. Despite investor dollars being hard to come by and the Biden administration pushing forward with its campaign to lower drug prices, the top biopharma firms still shelled out two orders of magnitude more money to CEOs than to median employees. Multiple companies have downsized their pipelines and operations, laying off thousands of workers across the industry. Some CEOs have even taken pay cuts to help the company’s bottom line. Famously, Pfizer’s Albert Bourla took a 35% reduction in compensation, with his pay dropping from $33 million in 2022 to $21.6 million last year. But while the ratio of Bourla’s salary to that of the company’s median employee lessened since 2022, he was still paid nearly 300 times the median salary, maintaining Pfizer’s spot near the top of BioSpace’s list. Big Biopharma Pay Gaps BioSpace highlights some of the largest ratios of CEO total compensation to median employee comp in 2023 1. Teva Pharmaceuticals | 398:1 CEO Richard Francis: $25,706,880 Median employee pay: $64,562 While CEO Richard Francis was not the highest-paid CEO in the industry in 2023, Teva’s employees made only a median of $64,562—the lowest on BioSpace’s top 9 list—granting the multinational company the top spot on the 2023 pay gap ranking. This is likely due in part to the fact that Teva is based in Israel, where the cost of living is lower than in the U.S. Teva, which filed a 2023 proxy statement with the SEC, is the only non-U.S. company included in this analysis. Teva had a strong 2023. The company made more than $15.8 billion, representing a 7% increase from its $14.9 billion revenue in the year prior. Mirroring this growth, the CEO compensation package jumped from $15.5 million in 2022—Kåre Schultz was the company’s chief at the time, before retiring in November 2022—to Francis’ total compensation of $25.7 billion in 2023. The cornerstone of Teva’s business is its generic products, which in 2023 brought in $3.48 billion, down 2% from 2022. Teva also saw declining sales for its multiple sclerosis therapy Copaxone and chronic lymphocytic leukemia chemotherapy Bendeka. These were offset by a 27% surge in the earnings of Austedo, its extended-release tablets for Huntington’s disease chorea and tardive dyskinesia. 2. Johnson & Johnson | 338:1 CEO Joaquin Duato: $28,422,037 Median employee pay: $84,000 With total compensation of $28.4 million, J&J head Joaquin Duato is the highest-paid CEO on this list, according to BioSpace’s analysis. Meanwhile, J&J’s median employee pay was comparatively low at $84,000, resulting in one of the industry’s widest pay gaps. Despite the expiration of key patent protections for its blockbuster antibody Stelara, J&J saw a 6.5% surge in revenues last year, which increased from almost $80 billion in 2022 to $85.16 billion in 2023. In turn, Duato received a large jump in compensation, which more than doubled from $13.1 million to $28.42 million—the highest pay hike of any CEO on BioSpace’s list. J&J’s growth was driven primarily by its cancer business, which grew by 10.5% to $17.7 billion in 2023. Stelara still reigned as the pharma’s most profitable asset, surging 11.7% to bring in $10.86 billion in sales. 3. Pfizer | 291:1 CEO Albert Bourla: $21,562,064 Median employee pay: $74,008 Despite his 35% pay cut, Pfizer’s Albert Bourla is still among the highest-paid CEOs in biopharma and earns nearly 300 times more than his company’s median employee does. Pfizer also has the second-lowest median employee pay in BioSpace’s ranking, once again contributing to the large pay gap ratio. Pfizer is among the pharma companies most severely affected by the dwindling COVID-19 market. In its full-year 2023 business report, the pharma posted a 42% decline, with revenues dropping from more than $100 billion in 2022 to $58.5 billion last year. In the third quarter of 2023, Pfizer recorded its first quarterly loss since 2019. To shore up its financial position, the company in October 2023 launched a sweeping cost-cutting initiative designed to save $3.5 billion through 2024. 4. Merck | 183:1 CEO Robert Davis: $20,273,287 Median employee pay: $110,827 At $20.2 million, Merck chief Robert Davis is one of the lowest-paid CEOs on this ranking, but he still got paid nearly 200 times more than the median employee in 2023. Merck owns Keytruda (pembrolizumab)—a PD-1 inhibitor indicated for several cancers—which was the industry’s top-selling asset last year, according to data analytics website Statista. In 2023, Keytruda’s sales grew 19% and brought in more than $25 billion, heavily contributing to Merck’s total revenue of $60.1 billion. 5. AbbVie | 169:1 CEO Richard Gonzalez: $25,661,972 Median employee pay: $151,991 Richard Gonzalez’s total compensation was nearly $25.7 million in 2023, a slight decrease from his pay of $26.2 million the year prior. This dip contributed to a smaller pay gap, with the ratio dropping from 224:1 to 169:1. AbbVie logged a total global net revenue of $54.3 billion in 2023, representing a 6.4% decrease from the year prior. The pharma attributed this decline to increasing biosimilar erosion for its blockbuster antirheumatic medication Humira. Currently there are at least five Humira biosimilars in the U.S. market. Despite increasing competition, Humira remained AbbVie’s best-performing asset last year, bringing in a worldwide total of $14.4 billion. 6. Eli Lilly | 168:1 CEO David Ricks: $26,565,732 Median employee pay: $157,937 With a total compensation of almost $26.6 million, Eli Lilly head David Ricks is the second most highly paid CEO on BioSpace’s list. This big paycheck heavily contributed to the pharma’s large pay gap, even though the median employee compensation of $157,937 was also relatively high. Lilly reported a full-year revenue of $34.1 billion in 2023, which corresponds to 20% growth, driven by the strong performance of its diabetes and obesity portfolio. The pharma’s type 2 diabetes drug Trulicity was its top asset, earning $7.1 billion last year, while Mounjaro, one of its fastest-growing products, raked in $5.2 billion. Despite only winning approval in November 2023, Lilly’s weight-loss treatment Zepbound still managed to bring in nearly $176 million. 7. Amgen | 136:1 CEO Robert Bradway: $22,643,650 Median employee pay: $166,322 At $166,322, Amgen had the second-highest median employee pay in 2023 of our top 9. In turn, despite a large compensation package of $22.6 billion for CEO Robert Bradway, the pharma found itself below some of its competitors in terms of pay gap. In 2023, Amgen posted nearly $28.2 billion in revenue, up from $26.3 billion in 2022. Much of this growth was driven by its postmenopausal osteoporosis therapy Evenity and acute lymphoblastic leukemia treatment Blincyto. The hyperlipidemia medication Repatha, which brought in $1.64 billion last year, also saw strong growth at 26%. Amgen’s best-selling asset in 2023 was the osteoporosis therapy Prolia, which earned over $4 billion. 8. Bristol Myers Squibb | 130:1 CEO Giovanni Caforio: $19,661,434 Median employee pay: $151,172 Before retiring in November 2023, former BMS chief Giovanni Caforio had a compensation package reaching almost $19.7 million, which is the lowest of the CEOs in BioSpace’s list. Meanwhile, the median employee pay at BMS last year was relatively high at $151,172, resulting in a comparatively small pay gap among these biopharma giants. Caforio was succeeded by former BMS COO Christopher Boerner. BMS brought in $45 billion in 2023, a 2% decline from its revenue in 2022. The pharma blamed the dip on the 39% plunge in sales of its multiple myeloma therapy Revlimid, which was only partially offset by the 10% jump in its cancer treatment Opdivo. BMS’ top asset last year was the anticoagulant Eliquis, which raked in more than $12.2 billion. 9. Gilead Sciences | 110:1 CEO: Daniel O'Day, $22,607,690 Median employee pay: $205,866 At over $205,000, Gilead’s median employee pay is the highest of all the companies on BioSpace’s top 9 list. Meanwhile, CEO Daniel O’Day brought in a relatively low total of $22.6 million. The pharma recorded a total global revenue of $27.1 billion in 2023, a slight drop from nearly $27.3 billion in 2022. Sales of Gilead’s COVID-19 antiviral treatment Veklury plunged 44% to $2.2 billion last year. The company made up for this drop through its HIV and oncology businesses, which grew by 6% and 37%, respectively. In its year-end report, the pharma revealed that its breast cancer therapy Trodelvy missed its primary endpoint in the Phase III EVOKE-01 study, failing to significantly improve overall survival versus docetaxel in non-small cell lung cancer. Pay Gaps Pervade Life Sciences Industries This year BioSpace’s analysis strictly focused on the top biopharma companies with SEC filings disclosing the pay gap ratio between CEO and median employee. It is worth noting that at least some foreign companies that don’t SEC forms, but for which we do have similar information, also had triple digit pay gaps. U.K.-based AstraZeneca, for example, reported a 182:1 ratio between its CEO’s remuneration and that of its median employee. This year’s list also excludes Viatris, which has not yet filed its proxy statement for 2023, but based on 2022 data would have topped the list with a ratio of 424:1. We also focused exclusively on biopharma companies this year, excluding service providers, financial firms and healthcare organizations. Many of these peripheral players would have topped the list otherwise. Bausch + Lomb, a consumer eye health company, would have easily claimed the top spot, with a pay gap ratio of almost 898:1. Volatility in Pay Gaps In the second year of doing this survey of CEO-employee pay gaps in biopharma, BioSpace noticed some extreme jumps in the data. Two interesting cases came from smaller biopharma companies that were eliminated from this year’s analysis due to their size, but wouldn’t have made the list anyway because their pay gaps fell considerably compared with 2022. While Sarepta Therapeutics and Biogen opened and closed last year’s top 20, with ratios of 494:1 and 182:1, respectively, those numbers were just 5:1 and 23:1 in 2023. Sarepta CEO Doug Ingram’s total comp was nearly $125 million in 2022, though his base salary was just over $740,000. The bulk of his compensation came from stock awards and options agreements. Without these extras, Ingram’s compensation fell to $1.66 million in 2023, comparable to 2021. Meanwhile, Biogen chief Christopher Viehbacher’s 2022 compensation was inflated by his $30.5-million sign-on package when he agreed to lead the pharma that November. Last year, Viehbacher’s pay was $4.1 million. Methodology In coming up with this report, BioSpace collected data from the SEC filings of the top U.S. biopharma companies by 2023 revenue to identify those firms with the widest pay gaps between the CEO and the median employee. We considered only those companies that filed Schedule 14a proxy statements reporting this information for 2023. Even still, the SEC allows a company to “select its methodology for identifying its median employee and that employee’s compensation,” as long as its methods are “reasonable.” As such, directly comparing pay gap ratios between companies could be inconclusive or misleading. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.