bosutinib / Generic mfg. - LARVOL DELTA

Asciminib (ASC) Demonstrates Favorable Safety and Tolerability Compared with Each Investigator-Selected Tyrosine Kinase Inhibitor (IS TKI) in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) in the Pivotal Phase 3 ASC4FIRST Study (ASH 2024) - "Introduction : About 1/3rd of patients (pts) with newly diagnosed CML discontinue/switch treatments (Tx) regardless of TKI (imatinib [IMA], nilotinib [NIL], dasatinib [DAS], or bosutinib [BOS]). ASC's superior efficacy vs all IS TKIs and more favorable safety/tolerability compared with each IS TKI (IMA, NIL, DAS, and BOS) suggests that ASC may transform the CML Tx paradigm. Key secondary endpoints, including MMR rate at wk 96, and other long-term secondary efficacy and safety/tolerability results, will be presented at ASH 2024."

Clinical • P3 data • Atherosclerosis • Cardiovascular • Chronic Myeloid Leukemia • Congestive Heart Failure • Coronary Artery Disease • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myocardial Infarction • Oncology • Pancreatitis • Respiratory Diseases • Thrombocytopenia

Adverse Respiratory Reactions to Tyrosine Kinase Inhibitors: A Disproportionality Analysis of Spontaneous Reports from European Countries. (PubMed, Life (Basel)) - "The results indicate that respiratory disorders induced by the TKIs dasatinib and bosutinib need to be diagnosed in a timely manner, and suggest that caution should be taken when prescribing these TKIs to patients affected by CML and pulmonary comorbidities."

Journal • Cardiovascular • Chronic Myeloid Leukemia • Hematological Malignancies • Hypertension • Leukemia • Oncology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Intramolecular Interactions of Twenty-Eight Amide Derivatives with the C-ALB Kinase using a Theoretical Model as a Therapeutic Alternative to Treat Cancer. (PubMed, Drug Res (Stuttg)) - "Besides, bosutinib, dasatinib, imatinib, nilotinib, and radotinib were used as controls in the DockingServer program.The results displayed different types of aminoacid residues involved in the interaction of amide derivatives with the 1iep protein surface compared to the controls. Finally, the Ki for amide derivatives 1, 19, and 21 were lower compared with bosutinib, dasatinib, imatinib, and nilotinib.Theoretical data indicate that amide derivatives such as 1, 15, 16, 18, 19, and 21 might have a higher affinity for the 1iep protein surface. This phenomenon could be translated as c-Abl kinase inhibition, resulting in a decrease in cancer cell growth."

Journal • Oncology • ABL1

Efficacy and Safety of Asciminib in Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Interim Results from the Phase 2 ASC2ESCALATE Trial in the Cohort of Patients (Pts) after 1 Prior Tyrosine Kinase Inhibitor (TKI) (ASH 2024) - P2 | "Pts had received prior treatment with imatinib (32.6%), dasatinib (48.8%), nilotinib (16.3%), or bosutinib (2.3%); 76.7% had received their prior TKI for ≥12 mo. These promising results support asciminib as a potential treatment option in these pts. Updated data (data cutoff June 28, 2024) will be presented at the ASH 2024 Annual Meeting."

Clinical • P2 data • Cardiovascular • Chronic Myeloid Leukemia • Cough • Fatigue • Hematological Malignancies • Hypertension • Leukemia • Oncology • Respiratory Diseases

ASCIMINIB (ASC) PROVIDES SUPERIOR EFFICACY AND EXCELLENT SAFETY AND TOLERABILITY VS TYROSINE KINASE INHIBITORS (TKI) IN NEWLY DIAGNOSED CHRONIC MYELOID LEUKEMIA (CML) IN THE PIVOTAL ASC4FIRST STUDY (EHA 2024) - P3 | "ASC, the first BCR::ABL1 inhibitor to Specifically Target theABL Myristoyl Pocket (STAMP), was intentionally designed to be highly specific and minimize off-target effects.We report primary results from ASC4FIRST (NCT04971226), a randomized ph 3 study of ASC vs all currentstandard-of-care frontline TKIs in pts with newly diagnosed CML.Aims:The two primary objectives were to demonstrate superior major molecular response (MMR) rate at wk 48 withASC vs investigator-selected (IS) TKI and ASC vs IS TKI within the stratum of pts with imatinib (IMA) as theirprerandomization-selected (PRS) TKI (ASCIMA vs IS TKIIMA). Pts received ASC (n=201: ASCIMA, n=101; ASC2G, n=100) or an IS TKI (n=204: IS TKIIMA, n=102; IS TKI2G,n=102 [nilotinib, 48%; dasatinib, 41%; and bosutinib, 11%]). Median follow-up was 16.3 and 15.7 mo with ASCand IS TKIs, respectively. At cutoff (Nov 28, 2023), Tx was ongoing in 86%, 62%, and 75% of pts receiving ASC,IMA, and 2G TKIs, respectively (Figure).MMR..."

Clinical • Anemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia

Cost Variation and Affordability of Oral Targeted Cancer Therapy in India: Comparison of Branded and Janaushadhi Products. (PubMed, Cureus) - "Percentage cost variation ranged from 8% (Bosutinib) to 14,774.74% (Midostaurin), with corresponding cost ratios up to 148.75...Absolute savings versus median branded costs ranged from ₹2,968 (Dasatinib) to ₹25,270 (Lapatinib), while percentage savings ranged from 58.89% (Dasatinib) to 91.32% (Imatinib)...However, limited PMBJP coverage restricts their overall benefit. Expanding Janaushadhi availability, improving price regulation, and encouraging rational prescribing are crucial to ensure equitable access to targeted cancer therapies in India."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Solid Tumor • ABL1 • BCR • CDK4

ASC4FIRST, a pivotal phase 3 study of asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly diagnosed patients (pts) with chronic myeloid leukemia (CML): Primary results. (ASCO 2024) - P3 | " Adults with CML were randomly assigned 1:1 to receive ASC 80 mg once daily or an IS TKI at standard label doses, stratified by ELTS risk category and prerandomization selected (PRS) TKI (imatinib [IMA] or second-generation [2G] TKIs), which was selected by investigators before randomization, accounting for pt preference... Pts received ASC (n=201: ASC IMA , n=101; ASC 2G , n=100) or IS TKI (n=204: IS TKI IMA , n=102; IS TKI 2G , n=102 [nilotinib, 48%; dasatinib, 41%; bosutinib, 11%])... ASC is the only agent to show a statistically significant superior efficacy and excellent safety and tolerability vs all current standard-of-care frontline Tx, with potential to be the therapy of choice for CML."

Clinical • Late-breaking abstract • P3 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Efficacy and safety of asciminib (ASC) in patients (pts) with chronic-phase chronic myeloid leukemia (CML-CP) after 1 tyrosine kinase inhibitor (TKI): Interim analysis (IA) of the phase 2 ASC2ESCALATE trial. (ASCO 2025) - P2 | "Prior treatment (Tx) included dasatinib (44.6%), imatinib (42.6%), nilotinib (9.9%), or bosutinib (5.0%); 66.3% of pts had received prior Tx for ≥12 mo. 2L ASC demonstrated high molecular response rates at wk 24 and safety consistent with previously established ASC data across Tx lines; no new or worsening safety signals arose. ASC was tolerable with few AEs leading to discontinuation. These IA results support ASC as a Tx option in 2L CML-CP."

Clinical • P2 data • Cardiovascular • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Neutropenia • Oncology • Pain • Thrombocytopenia

Assessment of Outcomes After Stopping Tyrosine Kinase Inhibitors Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial. (PubMed, JAMA Oncol) - P=N/A | "Participants were adults with chronic-phase CML whose disease was well controlled with imatinib, dasatinib, nilotinib, or bosutinib. Detectable BCR-ABL1 by RQ-PCR or ddPCR at the time of TKI discontinuation was associated with higher risk of MRec; clinical application of this finding should be confirmed in other studies. ClinicalTrials.gov Identifier: NCT02269267."

Clinical • Journal • Chronic Myeloid Leukemia • CNS Disorders • Depression • Fatigue • Hematological Malignancies • Leukemia • Oncology • Pain • Psychiatry • Sleep Disorder

Efficacy and Safety Results from ASC4MORE, a Randomized Study of Asciminib (ASC) Add-on to Imatinib (IMA), Continued IMA, or Switch to Nilotinib (NIL) in Patients (Pts) with Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Not Achieving Deep Molecular Responses (DMRs) with ≥1 Year of IMA (ASH 2022) - P2, P3 | "In the phase 3 ASCEMBL study, ASC led to superior major molecular response vs bosutinib (BOS) at wk 24 and 96...Top reasons for discontinuation were pt decision in the ASC 40-mg add-on arm (9.5%), AEs in the ASC 60-mg add-on and NIL arms (14.3% and 23.8%, respectively), and physician decision in the IMA arm (57.1%) (pts who crossed over to the ASC 60-mg add-on arm were considered discontinued for IMA arm)... More pts achieved DMR at wk 48 with ASC add-on to IMA vs continued IMA or switch to NIL in pts not achieving DMR with IMA alone for ≥1 y. In this population of pts tolerating IMA for ≥1 y, ASC add-on was generally well tolerated. While not powered to identify the best arm for achievement of DMR in this setting, the high rate of DMR in the ASC add-on arms is promising. Further studies are needed to assess if ASC alone can provide equivalent efficacy and better tolerability vs add-on to IMA."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Multiomics analysis reveals that senescent CXCL16+ macrophages promote lung adenocarcinoma progression through TGF-β signalling. (PubMed, J Transl Med) - "CXCL16 promotes macrophage senescence, and senescent CXCL16+ macrophages drive LUAD progression through TGF-β signalling. These findings identify CXCL16+ macrophages as a biologically and therapeutically relevant immune cell population, highlighting a potential target for precision intervention in LUAD."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDKN1A • CXCL16 • TGFB1

Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL. (PubMed, Leukemia) - "Fewer grade ≥3 adverse events (AEs) (56.4% vs 68.4%) and AEs leading to treatment discontinuation (7.7% vs 26.3%) occurred with asciminib than with bosutinib. A higher proportion of patients on asciminib than bosutinib remained on treatment and continued to derive benefit over time, supporting asciminib as a standard of care for patients with CML-CP previously treated with ≥2 TKIs."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Efficacy and safety results from ASCEMBL, a phase 3 study of asciminib versus bosutinib (BOS) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIs): Week 96 update. (ASCO 2022) - P3 | "After >2 years of follow-up, asciminib continued to show superior efficacy and better safety/tolerability vs BOS. Responses were durable, with more pts on asciminib in MMR. Additionally, more pts on asciminib had BCR::ABL1IS≤1%, a milestone response in later lines associated with improved survival."

Clinical • P3 data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia

Sustained Efficacy and Safety with Asciminib (ASC) after Almost 4 Years of Median Follow-up from Ascembl, a Phase 3 Study of ASC Vs Bosutinib (BOS) in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after ≥2 Prior Tyrosine Kinase Inhibitors (TKIs): An End of Study Treatment (EOS Tx) Update, Including Results from Switch Population (ASH 2023) - " Adults (aged ≥18 y) with CML-CP after ≥2 prior TKIs, with intolerance or lack of efficacy per 2013 ELN recommendations were randomized 2:1 to receive either ASC 40 mg twice daily or BOS 500 mg once daily. With almost 4 y of follow-up in ASCEMBL, ASC continued to show greater efficacy and better safety/tolerability than BOS in pts with CML-CP after ≥2 prior TKIs. The robust safety profile of ASC was sustained through each analysis in ASCEMBL (wk 24, wk 96, and EOS Tx), confirming that pts receiving ASC can maintain a high level of response and continue Tx without experiencing late-emerging AEs. Results in the switch population support the use of ASC early in the Tx paradigm."

Clinical • P3 data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia

Efficacy and Safety Results from Ascembl, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, Vs Bosutinib in Patients with Chronic Myeloid Leukemia in Chronic Phase after ≥2 Prior Tyrosine Kinase Inhibitors: Update after 48 Weeks (ASH 2021) - "Resistant/intolerant CML-CP after 2 lines of TKI treatment remains BCR-ABL1 dependent. The novel STAMP inhibitor asciminib demonstrates continued superior efficacy and a limited adverse event profile; myelosuppression, while more prominent, appears to be early and disease related. Secondary resistance based on loss of MMR is rare."

Clinical • P3 data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia • BCR

Asciminib vs bosutinib in CML patients pretreated with ≥2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study. (PubMed, Cancer Med) - P3 | "Findings from this Japanese subgroup analysis of the ASCEMBL study support the use of asciminib for the treatment of Japanese patients with CML-CP previously treated with ≥2 TKIs. ClinicalTrials.gov Identifier: NCT03106779."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Asciminib remained superior vs bosutinib in late-line CML-CP after nearly 4 years of follow-up in ASCEMBL. (PubMed, Blood Adv) - P3 | "These long-term results further solidify asciminib as the therapy of choice for patients with CML-CP previously treated with ≥2 prior TKIs. This trial was registered at ClinicalTrials.gov as NCT03106779."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Impact of Mutations in Blood Cancer–Related Genes on Clinical Outcomes in Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after ≥2 Tyrosine Kinase Inhibitors (TKIs) in the Ascembl Trial (ASH 2023) - "With >2 years of follow-up in the phase 3 ASCEMBL study, asciminib (ASC) has continued to demonstrate superior efficacy vs bosutinib (BOS) in pts with CML-CP after ≥2 prior TKIs, and analysis of cancer gene somatic mutations in this population has the potential to reveal additional insights into pts' response to study treatments or characteristics of the disease in later lines of therapy... Adults with CML-CP previously treated with ≥2 TKIs with intolerance of their last TKI or lack of efficacy per 2013 European LeukemiaNet recommendations and without BCR::ABL1 T315I or V299L mutations were randomized 2:1 to ASC 40 mg twice daily or BOS 500 mg once daily... ASXL1 mutations are most frequently detected at CML diagnosis and were enriched at BL in this study of pts with CML-CP previously treated with ≥2 TKIs, which is consistent with a role in TKI resistance. RUNX1 and IKZF1 mutations, which are associated with progression to accelerated or blast phase in CML, were..."

Clinical • Clinical data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ASXL1 • IKZF1 • RUNX1

A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After ≥2 Prior TKIs. (PubMed, Blood) - P3 | "These results support the use of asciminib as a new therapy in patients with CML-CP who are resistant or intolerant to ≥2 prior TKIs. The trial is registered at www.ClinicalTrials.gov as NCT03106779."

Clinical • Journal • P3 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Inotuzumab Ozogamicin with Bosutinib for Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia or Lymphoid Blast Phase of Chronic Myeloid Leukemia. (PubMed, Am J Hematol) - "No patient developed veno-occlusive disease. Inotuzumab ozogamicin with bosutinib was well tolerated in R/R Ph-positive ALL and LBP-CML."

Journal • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Dermatology • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Neutropenia • Oncology • Thrombocytopenia • Transplantation

Bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial. (PubMed, Leukemia) - P3 | "After 5 years of follow-up there was an increase in the incidence of cardiac, effusion, renal, and vascular TEAEs in bosutinib- and imatinib-treated patients, but overall, no new safety signals were identified. These final results support 400-mg once-daily bosutinib as standard-of-care in patients with newly diagnosed CP CML.This trial was registered at www.clinicaltrials.gov as #NCT02130557."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Efficacy and safety of bosutinib in previously treated patients with chronic myeloid leukemia: final results from the BYOND trial. (PubMed, Leukemia) - P4 | "The management of AEs through dose reduction maintained efficacy while improving tolerability. These results support the use of bosutinib in patients with previously treated CML.ClinicalTrials.gov, NCT02228382."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Physiologically Based Pharmacokinetic Modeling in Patients With Hepatic Impairment: Are Changes in Bosutinib Exposure Profiles Driven by Altered Absorption or Distribution? (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Bosutinib is a substrate of P-glycoprotein (P-gp) in vitro and is predominantly metabolized by CYP3A4 in humans with minimal urinary excretion. We present our perspective on using physiologically based pharmacokinetic modeling to understand the atypical changes in oral exposure of bosutinib, a CYP3A and P-gp substrate, in hepatic impairment patients."

Journal • PK/PD data • Chronic Myeloid Leukemia • Hematological Malignancies • Hepatology • Leukemia • Oncology • CYP3A4

Alembic Pharmaceuticals Limited has received tentative approval from the US Food and Drug Administration (USFDA) for its Bosutinib Tablets, 400 mg, the company said on Monday, January 12. (CNBC-TV18) - "In a regulatory filing, Alembic Pharma said the tentative approval has been granted for its supplemental Abbreviated New Drug Application (sANDA)....Bosutinib is a kinase inhibitor used in the treatment of adult patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML), including newly-diagnosed patients as well as those who are resistant or intolerant to prior therapies. It is also indicated for adult patients with accelerated or blast phase Ph+ CML who have shown resistance or intolerance to earlier treatments."

ANDA • Chronic Myeloid Leukemia

New Drug Therapies Against Targeting Neurodegenerative Diseases: A Comprehensive Review. (PubMed, Cent Nerv Syst Agents Med Chem) - "In Alzheimer's disease, specific antibodies targeting the β-amyloid protein (aducanumab, lecanemab, and others) are gaining special interest due to the approval of the first particular drugs against this disease...In amyotrophic lateral sclerosis, the appearance of newly approved drugs such as tofersen and edaravone, and some others in clinical Phase II (bosutinib), opens a new era in the understanding and treatment of this condition...In vascular dementia, numerous in vivo trials with molecules of different natures (flavonoids and lactones) have yielded positive results, delaying the progression of the disease. This review examines recent reports on molecules evaluated in vivo and in vitro models of the primary neurodegenerative diseases."

Journal • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia