Dasatinib

Growing improvement in major molecular response (MMR) rates demonstrated with Scemblix vs. all standard-of-care TKIs including imatinib and second generation (2G) TKIs 1 Clinically relevant 15.2% higher MMR rate achieved with Scemblix vs. 2G TKIs 1 Fewer grade ≥3 AEs and less than half the discontinuation rate due to AEs seen with Scemblix vs. imatinib and 2G TKIs 1 Basel, June 1, 2026 – Novartis today announced positive 144-week data from the pivotal ASC4FIRST trial of Scemblix ® (asciminib) presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. These results provide longer-term evidence that Scemblix demonstrated increasingly superior molecular responses at week 144 compared with established tyrosine kinase inhibitors (TKIs), strengthening confidence in its sustained response 1 . ASC4FIRST compared the MMR rate of Scemblix to investigator-selected (IS) standard-of-care (SoC) TKIs (imatinib and 2G TKIs nilotinib, dasatinib, and bosutinib) and to imatinib alone in adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) 2,3 . The longer-term data showed a progressively larger difference in MMR rates favorable to Scemblix vs. SoC TKIs, vs. imatinib and vs. 2G TKIs 1 . “Because CML patients often need to remain on therapy long term, treatments must combine robust efficacy with a favorable safety and tolerability profile,” said Jorge Cortes, M.D., Chief of Hematology, UAB O’Neal Cancer Center. “These data show asciminib continued to deliver significantly higher response rates versus the comparator TKIs and offers improved response that widens over time, including compared to second-generation TKIs.” “Drawing on more than 25 years in CML and a Scemblix clinical program of over 10 years, Novartis is focused on addressing treatment challenges for people living with CML,” said Mark Rutstein, M.D., Global Head, Oncology Development, Novartis. “With now nearly 3 years of extended follow-up in ASC4FIRST, we continue to see results that support Scemblix as an important option for newly diagnosed adult CML patients.” In addition to meeting all primary and key secondary endpoints at weeks 48 and 96, Scemblix continued to extend the treatment benefit for patients vs. SoC TKIs at week 144 1 ,2,3,4 . At the cutoff, more patients remained on treatment with Scemblix vs. SoC (78.6% vs. 55.9%), imatinib (81.2% vs. 50.0%), and 2G TKIs (76.0% vs. 61.8%) 1 . At week 144, nearly 24% more patients treated with Scemblix achieved MMR vs. all SoC TKIs, and over 32% more patients achieved MMR vs. imatinib alone 1 . The Scemblix MMR rate was 15.2% higher vs. 2G TKIs (75.0% vs. 59.8%; P=0.01*) 1 . Patients treated with Scemblix also achieved deeper molecular responses (MR4 and MR4.5) compared with SoC TKIs 1 . * Unadjusted nominal p-value for descriptive purposes only Overall a Scemblix (n=201) vs. IS SoC TKIs (n=204) Imatinib stratum b Scemblix (n=101) vs. imatinib (n=102) 2G TKI stratum c Scemblix (n=100) vs. 2G TKIs (n=102) Secondary objectives d MMR rates at week 144 77.1% vs. 53.4% 79.2% vs. 47.1% 75.0% vs. 59.8% MR4 at week 144 55.7% vs. 36.3% 58.4% vs. 33.3% 53.0% vs. 39.2% MR4.5 at week 144 42.3% vs. 24.5% 43.6% vs. 19.6% 41.0% vs. 29.4% a All patients receiving Scemblix (n=201) or IS SoC TKIs (n=204). Treatment difference after adjusting for pre-randomization selected TKI and EUTOS long-term survival (ELTS) risk groups at baseline. b The 203 patients within the pre-randomization-selected imatinib stratum were randomized to receive either Scemblix (n=101) or imatinib (n=102). Treatment difference after adjusting for ELTS risk groups at baseline. c The 202 patients within the pre-randomization selected 2G TKIs stratum were randomized to receive either Scemblix (n=100) or 2G TKIs (n=102: nilotinib, 48%; dasatinib, 41%; bosutinib, 11%). d Secondary objectives were not powered for statistical significance. “For many patients living with CML, managing a lifelong condition means balancing disease control with the real impact of treatment on daily life, and too often side effects can stand in the way of staying on therapy,” said Joannie Clements, CML patient and founder of CML Buster Foundation. “There remains a clear unmet need for treatments that are highly effective and also have a safety and tolerability pro enough to be suitable for long-term use.” Scemblix demonstrated a safety pro 144 weeks consistent with the 4-year follow-up of the Phase III ASCEMBL trial, with no new safety concerns observed to date 1 ,2,5 . Compared with both imatinib and 2G TKIs, Scemblix showed fewer grade ≥3 AEs, fewer dose adjustments to manage adverse events, and more than 50% lower discontinuation due to adverse events 2, 4 , 6 . The most frequent AEs (≥15%) were diarrhea, headache, fatigue, musculoskeletal pain, and rash 4,7 . Week 144 Scemblix n=200 Imatinib n=99 2G TKIs n=102 Grade ≥3 AEs a 49% 52% 63% Discontinuation due to AEs a 6% 13% 14% AEs leading to dose adjustments/interruptions a 37% 44% 63% a In patients who experienced ≥1 adverse event. These data will also be presented as an oral presentation at the European Hematology Association (EHA) 2026 Congress in June. About the ASC4FIRST Phase III Clinical Trial ASC4FIRST ( NCT04971226 ) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix ® 80 mg QD vs. IS first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP 2, 3 . The trial met both primary endpoints with Scemblix demonstrating superior MMR rates at week 48 vs. investigator-selected SoC TKIs (imatinib, nilotinib, dasatinib, and bosutinib) (67.7% vs. 49.0%) and imatinib alone (69.3% vs. 40.2%) as well as the secondary, non-powered endpoint for the 2G TKI stratum of (66% vs. 57.8%) 3 . The study remains ongoing with further efficacy and safety readouts planned. About Scemblix ® (asciminib) Scemblix ® is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature) 5,8 ,9 . Other currently approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive) 9 . In the US, Scemblix was granted accelerated approval to treat newly diagnosed adults with Ph+ CML-CP. Outside the US, Scemblix is approved to treat newly diagnosed adults with Ph+ CML-CP in more than 60 countries, including the EU, China, and Japan. It is also approved in 61 countries, including the US and the EU, for previously treated adults with Ph+ CML-CP, regardless of prior therapy, and in 58 countries, including the US and the EU, for patients with Ph+ CML-CP with the T315I mutation 1 0 . About Novartis Commitment to CML Novartis has a long-standing scientific commitment to patients living with CML. For more than 25 years, our bold science has helped transform CML from a life-limiting condition for many patients. Despite these advancements, there’s still work to be done. We continue to research ways to target the disease more selectively and to address the challenges of not reaching treatment efficacy goals, experiencing treatment resistance and/or intolerance that many patients face. Our legacy inspires our future innovation. Disclaimer This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. 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In particular, our expectations could be affected by, among other things, uncertainties concerning: global healthcare cost containment, including ongoing government, payer and general public pricing and reimbursement pressures and requirements for increased pricing transparency; the success of our key products, commercial priorities and strategy; research and development of new products, including clinical trial results and additional analysis of existing clinical data; our ability to obtain or maintain proprietary intellectual property protection, including the ultimate extent of the impact on Novartis of the loss of patent protection and exclusivity on key products; our ability to realize the strategic benefits, operational efficiencies or opportunities expected from our external business opportunities; the development or adoption of new technologies, including artificial intelligence, and new business models; potential significant breaches of information security or disruptions of our information technology systems; actual or potential legal proceedings, including regulatory actions or delays or government regulation related to the products and pipeline products described in this press release; safety, quality, data integrity, or manufacturing issues; major macroeconomic and geo- and socio-political developments, including the impact of any potential tariffs on our products or the impact of war in certain parts of the world; future global exchange rates; future demand for our products; and other risks and factors referred to in Novartis AG’s most recently filed Form 20-F and in subsequent reports filed with, or furnished to, the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 300 million people worldwide. Reimagine medicine with us: Visit us at and connect with us on LinkedIn , Facebook , X/Twitter and Instagram . References Cortes JE, Hochhaus A, Hughes TP, et al. ASC4FIRST wk 144 analysis: continued superior efficacy and favorable safety and tolerability with asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly diagnosed (ND) chronic myeloid leukemia in chronic phase (CML-CP). Presented at: The 2026 ASCO Annual Meeting; May 29 – June 2, 2026; Chicago, IL Scemblix. Prescribing information. Novartis Pharmaceuticals Corp. Data on file. CABL001J12301 clinical study report (Week 48 analysis). Novartis Pharmaceuticals Corp; 2024. Data on file. CABL001J12301 clinical study report (Week 96 analysis). Novartis Pharmaceuticals Corp; 2024. Rea D, Mauro MJ, Boquimpani C, et al. A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After 2 or more prior TKIs.  Blood.  2021;138(21):2031-2041. doi:10.1182/blood.2020009984  Cortes JE, Hochhaus A, Hughes TP, et al. Asciminib Continues to Provide Superior Efficacy and Favorable Safety and Tolerability vs Tyrosine Kinase Inhibitors In Newly Diagnosed Chronic Myeloid Leukemia in ASC4FIRST: Week 96 Update. Presented at: 66th ASH Annual Meeting & Exposition; December 7 – 10, 2024; San Diego, CA. Data on file. ABL001J1 SCS Appendix 2. Novartis Pharmaceuticals Corp; 2025. Cortes JE, Hughes TP, Mauro MJ, et al. Asciminib, a First-in-Class STAMP Inhibitor, Provides Durable Molecular Response in Patients (pts) with Chronic Myeloid Leukemia (CML) Harboring the T315I Mutation: Primary Efficacy and Safety Results from a Phase 1 Trial. Oral presentation at: ASH Annual Meeting; Dec. 7, 2020. Schoepfer J, Jahnke W, Berellini G, et al. Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1. J Med Chem. 2018;61(18):8120-8135. doi:10.1021/acs.jmedchem.8b01040 Novartis data on file. # # # Novartis Media Relations E-mail: media.relations@novartis.com Novartis Investor Relations Central investor relations line: +41 61 324 7944 E-mail: investor.relations@novartis.com

Targeting senescent cells with dasatinib–quercetin preserves disc structure and modulates degeneration-associated pathways in a mouse model CHINA, May 25, 2026 / EINPresswire.com / -- Early-onset intervertebral disc degeneration is partly driven by cellular senescence, yet effective disease-modifying therapies remain limited. Researchers report that the senolytic combination dasatinib and quercetin reduces senescence markers, inflammatory signaling, and degenerative tissue changes in a genetic mouse model of disc disease. In contrast, navitoclax shows no benefit. The study identifies JNK (c-Jun N-terminal kinase) signaling as a key pathway underlying disease progression and therapeutic response, highlighting a potential strategy for slowing spinal disc degeneration. Intervertebral disc degeneration is a major cause of chronic back and neck pain, yet current treatments largely focus on symptom relief rather than preventing disease progression. A growing body of evidence suggests that cellular senescence, where cells lose proliferative capacity and secrete inflammatory factors, plays a central role in accelerating disc tissue breakdown. However, how genetic susceptibility influences early disease onset and whether senescence-targeting therapies can alter this trajectory has remained poorly understood. To address this challenge, a research team led by the James J. Maguire Jr. Professor Makarand V. Risbud from the Department of Orthopaedic Surgery at Sidney Kimmel Medical College, Thomas Jefferson University, USA, investigated whether senolytic therapies could delay degeneration in SM/J mice, a model of spontaneous early-onset disc disease. The researchers compared two approaches: navitoclax, which targets BCL-2 family survival proteins, and a combination of dasatinib and quercetin (DQ), a widely studied senolytic cocktail. Their findings were published on April 14, 2026, in Volume 14 of the journal Bone Research . Using histological, molecular, imaging, and transcriptomic analyses, the team systematically evaluated structural, cellular, and molecular changes in intervertebral discs over time. They found that SM/J mice exhibited elevated senescence markers as early as four weeks of age, preceding overt structural degeneration. This early senescence burden was accompanied by inflammatory activation and gene expression changes linked to stress and extracellular matrix remodeling. “Importantly, early molecular changes preceded visible tissue damage, suggesting that senescence is not just a consequence of degeneration but a driving force in genetically susceptible discs,” explained Prof. Risbud. Treatment with dasatinib–quercetin significantly reduced disc degeneration severity compared with untreated controls. Mice receiving DQ showed improved preservation of nucleus pulposus structure, reduced degenerative remodeling, lower expression of senescence markers such as p19ARF and p21, and decreased inflammatory signaling. Importantly, these benefits were not observed to the same extent with navitoclax, which failed to improve either molecular or structural outcomes. A deeper transcriptomic analysis revealed that DQ treatment reshaped gene expression programs related to inflammation, stress responses, and cell cycle regulation, consistent with reduced senescence and improved tissue homeostasis. Further computational and functional analyses implicated JNK (c-Jun N-terminal kinase) signaling as a central pathway associated with disease progression and therapeutic response. “These data point to JUN signaling as a convergence hub linking senescence, inflammation, and extracellular matrix breakdown, helping explain why pathway-specific modulation by dasatinib–quercetin is effective,” Prof. Risbud noted. Functional experiments using human degenerated disc cells supported these findings. Inhibition of JUN signaling recapitulated key effects of DQ treatment, reducing senescence-associated β-galactosidase activity and lowering inflammatory gene expression. These results suggest that JUN signaling may act as a regulatory hub connecting senescence, inflammation, and tissue degeneration in the intervertebral disc. Beyond mechanistic insights, the study highlights broader implications for musculoskeletal aging and regenerative medicine. In the short term, these findings improve understanding of how genetic susceptibility interacts with cellular senescence to drive early disc degeneration. In the longer term, they may guide development of targeted senotherapeutic strategies aimed at slowing disease progression in at-risk individuals before irreversible tissue damage occurs. The research also underscores that senolytic efficacy is highly context-dependent, with different drugs producing distinct outcomes depending on tissue type and underlying molecular pathways. This could influence future therapeutic design, shifting attention toward pathway-specific interventions rather than broad senescent cell elimination. Overall, the study provides preclinical evidence that dasatinib–quercetin can delay early disc degeneration by suppressing senescence-associated pathways, preserving disc structure, and reducing inflammation and fibrotic tissue changes, with JUN signaling emerging as a potential therapeutic target. *** Reference Title of original paper: Dasatinib and quercetin senolytic treatment delays early onset intervertebral disc degeneration in SM/J mice Journal: Bone Research DOI: 10.1038/s41413-026-00526-4 About Thomas Jefferson University, USA Thomas Jefferson University, located in Philadelphia, USA, is a nationally recognized academic health sciences institution known for its excellence in medical education, biomedical research, and clinical innovation. The university integrates advanced research with patient-centered healthcare through its renowned Sidney Kimmel Medical College and affiliated hospitals. It fosters interdisciplinary collaboration across medicine, engineering, and life sciences to address complex health challenges. With a strong emphasis on translational research, Jefferson advances discoveries from laboratory to clinical application, particularly in areas such as cancer, neuroscience, and musculoskeletal disorders. The institution is committed to improving health outcomes locally and globally. Website: https://www.jefferson.edu/ About Professor Makarand V. Risbud from Thomas Jefferson University Prof. Makarand V. Risbud is the James J. Maguire Jr. Professor of Spine Research and Director of Orthopedic Research at Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, USA. He earned his PhD from the National Center for Cell Science, India in 2001, followed by postdoctoral training at Harvard University from 2001 to 2002. His research focuses on intervertebral disc biology, particularly nucleus pulposus cell adaptation to hypoxia and osmotic stress. He investigates transcriptional regulators, alongside regenerative strategies using mesenchymal stem cells. His work is highly translational, aiming to develop therapies for disc degeneration and spine disorders. Funding Information This study is supported by the grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01AR055655, R01AR064733, and R01AR074813, and the Michael Michelson Gift Fund to MVR. EJN received a PhD fellowship (PD/BD/128077/2016) from the MD/PhD Program at the University of Minho, funded by the Fundação para a Ciência e a Tecnologia (FCT). Yini Bao Bone Research Editorial Office +862885546461 ext. email us here Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. 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