Zanubrutinib

Jaypirca significantly reduced the risk of progression or death by 80% compared with the traditional regimen of bendamustine and rituximab in patients with previously untreated chronic lymphocytic leukemia. In the world of oncology drug development, the standard playbook is simple: Race to earlier lines of treatment, where patient populations are larger. But Eli Lilly is flipping that script with its blood cancer offering, Jaypirca.Despite holding positive phase 3 data that position its BTK inhibitor Jaypirca for a first-line approval in chronic lymphocytic leukemia (CLL), Jacob Van Naarden, president of Lilly Oncology, maintained that the drug’s primary value proposition remains in serving patients who require second-line treatment. “The main use case of the medicine, I think, remains in second-line,” Van Naarden said in an interview with Fierce Pharma.Lilly is defying the typical earlier-is-better strategy of cancer drug commercialization, but not because Jaypirca’s first-line data are weak. In fact, results from two phase 3 studies unveiled at the American Society of Hematology (ASH) 2025 annual meeting suggest Jaypirca could be a competitive first-line drug in CLL, posing a threat to existing BTK inhibitors from BeOne Medicines, AstraZeneca, and a partnership between AbbVie and Johnson & Johnson.Jaypirca significantly reduced the risk of progression or death by 80% compared with the traditional regimen of bendamustine and rituximab (BR) in patients with previously untreated CLL or small lymphocytic lymphoma (SLL), according to data from the Bruin CLL-313 trial presented at ASH on Dec. 9.At two years, an estimated 93% of patients who received Jaypirca were still alive without progression, versus 71% for those on BR. The median follow-up time of the data was about 28 months.Progression-free survival (PFS) benefits of Jaypirca were consistent across patient subpopulations, with an effect size around or above 70% for every prespecified subgroup analyzed.That data set immediately drew a comparison to results from the phase 3 Sequoia trial of BeOne’s Brukinsa, which recently became the best-selling BTK by quarterly sales. In that first-line CLL/SLL study, Brukinsa improved PFS by 58% compared with, BR with a median follow-up of about 26 months. After a long-term, median five-year follow-up, Brukinsa’s PFS benefit increased to 71%.“These data suggest [Jaypirca] could be an option for 1L CLL patients and may command a larger market presence than was previously anticipated,” Leerink Partners analysts said in a Nov. 24 note when ASH released the top-line Bruin CLL-313 data in a late-breaking abstract. In another phase 3 study, coded Bruin CLL-314, Jaypirca showed a numerically higher overall response rate of 87% compared with 78.5% for AbbVie and J&J’s aging Imbruvica in CLL/SLL patients who were treatment-naïve or were new to a BTK inhibitor. PFS results were not mature in the head-to-head study yet, but so far strongly favored Jaypirca by a risk reduction of 43% in the overall population or 76% in the first-line subgroup, according to investigators’ assessments. The rate of cardiovascular side effects—specifically atrial fibrillation and flutter—which are known problems with Imbruvica, was notably lower in the Jaypirca group, at 2.4% at any grade, versus 13.5% for Imbruvica. Similarly, in the Bruin CLL-313 trial, this rate was 1.4% for the Jaypirca arm and 1.5% for BR. For context, BeOne’s Brukinsa showed a 3.3% rate in Sequoia after a similar follow-up period.Despite the impressive first-line data, Lilly’s Van Naarden argued that Jaypirca’s value lies not in displacing entrenched first-line options, but in serving as a unique option in the second-line setting. “What Jaypirca can do in second-line, none of the other BTKs can do,” he said.Van Naarden has held that view ever since Jaypirca delivered its pivotal data in relapsed or refractory CLL three years ago.CLL patients are typically diagnosed at a relatively old age. And, because of how well BTK drugs can control the disease, the vast majority of CLL patients may get just two lines of therapy before they die of other causes. As a result, doctors want to have a reliable second-line option, Van Naarden explained. Jaypirca, as the first nonvalent, reversible BTK inhibitor, is currently the only BTK med approved for use after other covalent BTK inhibitors. For now, there’s no conclusive evidence on whether a covalent BTK inhibitor can be used after a noncovalent counterpart, an important data gap that Van Naarden acknowledged needs to be addressed. Additional Bruin CLL-313 results might provide some answers to that question, but, with only 13 (9.2%) patients having progressed following Jaypirca by the data cutoff, more follow-up is needed to offer any meaningful information, the Lilly exec noted. Without that, most doctors, while trying to preserve treatment options for relapsed patients, are expected to save Jaypirca for the second line.That is not to say that Jaypirca won’t get any first-line use if approved. Doctors may estimate that some patients might only ever get one line of therapy, while some doctors are comfortable using AbbVie and Roche’s Venclexta in the second-line setting, Van Naarden said. In addition, some docs may want to be mindful of the cardiovascular toxicity profiles of the various options.“When you add it all together, do I think Jaypirca will be the dominant player in first-line? No, I don’t. That’s never been our thesis, and I’m sticking with it,” Van Naarden said. “But I think that these data are good enough that it will make people think about it in certain situations.” Lilly is now bringing the data to the FDA for potential filing discussions. But a couple of uncertainties remain for the company’s regulatory path.First, the two phase 3 trials only included a small number of U.S. patients. In Bruin CLL-313, only seven (2.5%) patients were from North America. In Bruin-CLL-314, the proportion was 7.1%. In rejecting a combo of Roche’s Columvi for the second-line treatment of another blood cancer, diffuse large B-cell lymphoma, the FDA highlighted a lack of representation of the U.S. population, along with inconsistent data in U.S. patients compared with those in Asia.Jaypirca’s situation is different, Van Naarden argued. Columvi’s case was anchored on a large Asian population and data discordance across geographies. Jaypirca’s trials enrolled many patients from Europe, and their data are consistent across regions.There’s also a possibility that the FDA may want to see longer-term data. Overall survival data from Bruin CLL-313 were immature but favored Jaypirca, with a preliminary 74% reduction in the risk of death versus BR despite a 53% crossover rate. However, BR is a weak comparator in the first-line setting, which might explain the low U.S. enrollment. And PFS data from the Imbruvica head-to-head trial, Bruin CLL-314, remained immature.Lilly will submit the data and get the FDA’s reaction, Van Naarden said. “I think the data are objectively strong and, in many ways, better than my expectations going into them.”

SAN CARLOS, Calif.--(BUSINESS WIRE)--BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology company, reaffirms its position as the leader in chronic lymphocytic leukemia (CLL) innovation by showcasing the depth, quality, and momentum of its hematology portfolio at the 67th ASH Annual Meeting and Exposition in Orlando, Florida. The totality of BeOne’s ASH data reinforce BRUKINSA® (zanubrutinib) as the foundational Bruton’s tyrosine kinase inhibitor (BTKi) of choice. “At ASH 2025, we will present new data from across our CLL franchise, highlighting both the strength of BRUKINSA and the potential of BGB-16673,” said Amit Agarwal, M.D., Ph.D., Chief Medical Officer, Hematology, BeOne. “Long-term data are the gold standard in CLL, and BRUKINSA continues to deliver the high levels of durable progression-free and overall survival that patients and physicians should demand from a BTK inhibitor. BGB-16673, the most advanced BTK degrader in the clinic with over 800 patients dosed to date, potentially represents the next wave of foundational innovation in oncology.” BRUKINSA continues to demonstrate unprecedented long-term efficacy with a favorable safety profile over more than six years of follow-up in treatment-naïve CLL/SLL. In SEQUOIA (NCT03336333), a randomized, multicenter, global Phase 3 trial, BRUKINSA maintained progression-free survival (PFS) superiority versus bendamustine plus rituximab (BR) with an estimated 74% PFS at six years in treatment-naïve CLL or small lymphocytic lymphoma (SLL) compared with 32% PFS for BR. Highlights include: COVID-19 adjusted PFS rates were 77% (95% CI, 70.1-81.8) for BRUKINSA and 33% (95% CI, 25.5-40.4) for BR. The overall survival (OS) at 72 months was 84% for BRUKINSA and 80% with BR. After adjusting for COVID-19, the OS rates were 88% and 82%, respectively. In patients with del(17p), the six-year PFS was 64% (65% after COVID-19 adjustment) and the 72-month OS was 83%. The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified. “SEQUOIA’s longer follow-up strengthens the evidence for continuous zanubrutinib use,” said Constantine Tam, M.B.B.S., M.D., Head of Lymphoma Service at Alfred Health and Professor of Haematology at Monash University. “Patients continued to show durable disease control and consistent safety across study arms, meaningfully raising the bar for CLL patients, including those with harder-to-treat CLL.” In the overall patient population, in which 58% of patients had del(17p) and/or TP53 mutation, the median PFS was not reached; the 36-month PFS rate was 87%. The 36-month PFS rate for patients with del(17p) and/or TP53 mutation was 87% and for patients without del(17p) and TP53 mutation was 89%. A total of 42 patients completed the BRUKINSA plus venetoclax combination and continued BRUKINSA monotherapy. At 12 months following the combination period, peripheral blood undetectable minimal residual disease (uMRD) was maintained in 100% (18/18) of patients without del(17p) and TP53 . At 18 months following the combination period, uMRD was maintained in 92% (22/24) of patients with del(17p) and/or TP53 mutation. The safety profile of BRUKINSA plus venetoclax was generally tolerable and no unexpected safety signals were identified. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ® ) now recommend zanubrutinib plus venetoclax as a preferred first-line regimen for CLL/SLL. New patient-reported outcomes data in R/R CLL suggest BRUKINSA may offer a more manageable side effect profile. Up to six-years of follow-up data support BRUKINSA’s foundational role in CLL/SLL as the only BTK inhibitor with enduring PFS and long-term benefit over another BTK inhibitor. ALPINE (NCT03734016) is a global, randomized, open-label, multicenter, Phase 3 study of BRUKINSA versus ibrutinib in patients with R/R CLL/SLL who received ≥1 prior systemic therapy. Highlights include: This study is among the first analyses of patients with CLL/SLL to demonstrate a statistically and clinically meaningful association between longitudinal symptom deterioration and disease progression using joint modeling. Deterioration in patient-reported fatigue, insomnia, and nausea/vomiting emerged as strong symptomatic indicators of disease progression. Compared with ibrutinib, patients on BRUKINSA showed reduced risk of symptom deterioration associated with earlier disease progression. The analysis showed that patients on BRUKINSA had lower odds of symptom worsening for nausea/vomiting, fatigue, pain, and insomnia. With up to 73.5 months of follow-up, the median PFS for all patients was a striking 52.5 months; the 60-month PFS rate was 47.3% (50.4% adjusted for COVID-19). These results redefine what is expected for this patient population. Among patients with del(17p), the median PFS was 49.9 months; the 60-month PFS rate was 38.2% (40.5% adjusted for COVID-19). With longer follow-up, the prevalence of most adverse events of special interest remained stable year-over-year. BGB-16673 (BTK degrader) clinical data demonstrates rapid, robust and deepening responses in patients with heavily pretreated R/R CLL/SLL, including those with prior BTKi treatment and mutations that confer resistance to BTK inhibitors. (Oral Presentation: 85) Updated results from CaDAnCe-101 (NCT05006716), an ongoing open-label, Phase 1/2 study evaluating BGB-16673 monotherapy in patients with B-cell malignancies, showed responses across R/R CLL/SLL patient types, including those who had previously been treated with BTK inhibitors, BCL2 inhibitors, noncovalent BTK inhibitors, and those with BTK inhibitor resistance mutations. Highlights include: With a median follow-up of 19.8 months, 54.4% of patients remain on treatment. Across all doses, ORR was 85.3% and CR/CR with incomplete count recovery (CRi) rate was 2.9% with responses deepening over time. In the group of patients dosed at the recommended phase 2 dose (RP2D; 200 mg QD), ORR was 94.4%. In the patients with prior covalent BTK inhibitor, BCL2i, and noncovalent BTK inhibitor treatment, ORR was 75.0%. In the group of patients dosed at the recommended phase 2 dose (RP2D; 200 mg QD), ORR was 94.4%. In the patients with prior covalent BTK inhibitor, BCL2i, and noncovalent BTK inhibitor treatment, ORR was 75.0%. The 12- and 18-month PFS rates were 73.5% and 65.9% respectively. BGB-16673 was generally well tolerated in this heavily pretreated population with no treatment-related deaths and no new toxicities identified with a median treatment duration of 13.6 months. For more information about our presence at the 2025 ASH Annual Meeting and Exposition, please visit our meeting hub: congress.beonemedicines.com. About Chronic Lymphocytic Leukemia Chronic lymphocytic leukemia (CLL) is a life-threatening cancer of adults. It 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.2,3 About BGB-16673 BGB-16673 is a potential first-in-class Bruton’s tyrosine kinase (BTK) protein degrader and is the most advanced protein degrader in the clinic, with nearly 800 patients dosed to date in an extensive global clinical development program. This program includes three randomized Phase 3 trials in R/R CLL, including the head-to-head Phase 3 trial versus pirtobrutinib, which began enrolling in Q4 2025. Originating from BeOne’s chimeric degradation activation compound (CDAC) platform, BGB-16673 is designed to promote the degradation, or breakdown, of both wildtype and mutant forms of BTK, including those that commonly result in resistance to BTK inhibitors in patients who experience progressive disease. The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to BGB-16673 for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), and adult patients with R/R mantle cell lymphoma (MCL). Additionally, the European Medicines Agency (EMA) granted BGB-16673 PRIority MEdicines (PRIME) designation for the treatment of patients with Waldenstrom’s macroglobulinemia (WM) previously treated with a BTK inhibitor. 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. BRUKINSA is also the only BTK inhibitor to demonstrate superiority to another BTK inhibitor in a Phase 3 study. The global BRUKINSA clinical development program includes about 7,100 patients enrolled in 30 countries and regions across more than 35 trials. BRUKINSA is approved in more than 75 markets, and more than 247,000 patients have been treated globally. Select Important Safety Information Serious adverse reactions, including fatal events, have occurred with BRUKINSA, including hemorrhage, infections, cytopenias, second primary malignancies, cardiac arrhythmias, and hepatotoxicity (including drug-induced liver injury). In the pooled safety population (N=1729), the most common adverse reactions (≥30%), including laboratory abnormalities, in patients who received BRUKINSA were neutrophil count decreased (51%), platelet count decreased (41%), upper respiratory tract infection (38%), hemorrhage (32%), and musculoskeletal pain (31%). Please see full U.S. Prescribing Information including U.S. Patient Information. The information provided in this press release is intended for a global audience. Product indications vary by region. About BeOne BeOne Medicines is a global oncology company domiciled in Switzerland that is discovering and developing innovative treatments that are more accessible to cancer patients worldwide. With a portfolio spanning hematology and solid tumors, BeOne is expediting development of its diverse pipeline of novel therapeutics through its internal capabilities and collaborations. With a growing global team of nearly 12,000 colleagues spanning six continents, the Company is committed to radically improving access to medicines for far more patients who need them. To learn more about BeOne, please visit www.beonemedicines.com and follow us on LinkedIn, X, Facebook and Instagram. Forward-Looking Statement 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 potential benefits of BRUKINSA and BGB-16673; and BeOne’s plans, commitments, aspirations and goals under the caption “About BeOne.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeOne’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; BeOne’s ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeOne's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeOne’s reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeOne’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products; BeOne’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 BeOne’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeOne’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 BeOne undertakes no duty to update such information unless required by law. To access BeOne media resources, please visit our Newsroom. 1 National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ)–Patient Version. Accessed November 2024. 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 2024. 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 November 2024. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/key-statistics.html.