DaunoXome (liposomal daunorubicin) / SOBI, Galen - LARVOL DELTA

Venetoclax Enhances the Efficacy of the DA Treatment Regimen By Targeting Quiescent Leukemia Stem Cells (ASH 2024) - "BackgroundOur previous research introduced an effective induction treatment of venetoclax plus daunorubicin and cytarabine (DAV regimen), which showed high CR rates of 91% after one cycle of induction therapy in newly diagnosed young adult patients with AML...In comparison to the DA regimen, the DAV therapy exhibited more potent inhibition of the HOXA gene family, whose high expression is known to be linked to LSCs. Venetoclax inhibits cell viability and promotes cell apoptosis as well as cell cycle entry in LSCs, providing new insight in eradication of quiescent leukemia stem cells."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • PINK1

HPMA nanomedicine: targeting cancer with precision. (PubMed, J Mater Chem B) - "Abraxane, Myocet, DaunoXome, and Doxil are some examples of successful polymeric nanocarriers approved for cancer treatment. In addition, we present the clinical status and future prospects of pHPMA in combination with immunotherapy. We aim to provide comprehensive insights into the current pHPMA nanotherapeutics to facilitate future development."

Journal • Review • Oncology

Effect of Micromixer Design on Lipid Nanocarriers Manufacturing for the Delivery of Proteins and Nucleic Acids. (PubMed, Pharmaceutics) - "The suitable application of the platform was investigated by producing neutral, stealth and cationic liposomes, using DaunoXome®, Myocet®, Onivyde® and Onpattro® as the benchmark. The effect of condensing lipid (DOTAP, 3-10-20 mol%), coating lipids (DSPE-PEG550 and DSPE-PEG2000), as well as structural lipids (DSPC, eggPC) was pointed out. A very satisfactory encapsulation efficiency, always higher than 70%, was successfully obtained for model biomolecules (myoglobin, short and long nucleic acids)."

Journal • MB

Mitoxantrone Versus Liposomal Daunorubicin in Induction of Pediatric AML With Risk Stratification Based on Flow Cytometry Measurement of Residual Disease (J Clin Oncol) - P3 | N=300 | AML2012 (NCT01828489) | "Outcome for all 287 children was good with 5-year event-free survival (EFS5y) 66.7% (CI, 61.4 to 72.4) and 5-year overall survival (OS5y) 79.6% (CI, 75.0 to 84.4). Overall, 75% were stratified to standard-risk and 19% to high-risk. There was no difference in the proportion of patients with MRD <0.1% on day 22 after induction 1 (34% mitoxantrone, etoposide, araC [MEC], 30% DNX, P = .65), but the proportion increased to 61% for MEC versus 47% for DNX (P = .061) at the last evaluation before induction 2. EFS5y was significantly lower, 56.6% (CI, 46.7 to 66.5) versus 71.9% (CI, 63.0 to 80.9), and cumulative incidence of relapse (CIR) was higher, 35.1% (CI, 25.7 to 44.7) versus 18.8% (CI, 11.6 to 27.2) for DNX."

P3 data • Acute Myelogenous Leukemia

Cardiolipin for Enhanced Cellular Uptake and Cytotoxicity of Thermosensitive Liposome-Encapsulated Daunorubicin toward Breast Cancer Cell Lines. (PubMed, Int J Mol Sci) - "Daunorubicin (DNR) and cardiolipin (CL) were co-delivered using thermosensitive liposomes (TSLs). The liposomes also exhibited ~4-fold higher cytotoxicity against MDA-MB-231 cells compared to DNR or liposomes similar to DaunoXome (p < 0.001). This study provides a basis for developing a co-delivery system of DNR and CL encapsulated in liposomes for treatment of breast cancer."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

pH-Sensitive Liposomes for Enhanced Cellular Uptake and Cytotoxicity of Daunorubicin in Melanoma (B16-BL6) Cell Lines. (PubMed, Pharmaceutics) - "Daunorubicin (DNR) was delivered using a pH-sensitive liposomal system in B16-BL6 melanoma cell lines for enhanced cytotoxic effects. Furthermore, the CL liposomes exhibited 12.5- and 2.5-fold higher cytotoxicity compared to DNR or liposomes similar to DaunoXome. This study provides a basis for developing DNR pH-sensitive liposomes for melanoma treatment."

Journal • Preclinical • Melanoma • Oncology • Solid Tumor

[VIRTUAL] CLEARANCE OF PHENOTYPICALLY DISTINCT FLT3-ITD AND FLT3-TKD CLONES BY TREATMENT WITH CRENOLANIB AND CHEMOTHERAPY AS DETECTED BY LONGITUDINAL SINGLE-CELL DNA SEQUENCING ANALYSIS (EHA 2020) - P2 | "This patient was treated with cytarabine/daunorubicin/crenolanib induction, four cycles of HiDAC/crenolanib consolidation and one year of crenolanib maintenance as part a Phase II clinical trial (NCT02283177)...The use of the Tapestri Platform allowed detection of rare populations of distinct clones that have not been identified by other sequencing techniques. This case highlights the clonal dynamics of FLT3 AML and provides insights on strategies to optimize treatment."

Oncology • DNMT3A • FLT3 • KRAS • NPM1 • NRAS

Boosting Nanomedicine Efficacy with Hyperbaric Oxygen Therapy. (PubMed, Adv Exp Med Biol) - "Thus, it is more practical to find solutions to promote the therapeutic efficacy of commercialized nanomedicines, for example, Doxil, Oncaspar, DaunoXome, Abraxane, to name a few. Inspired by this study, we further carried out researches on the combination of HBO therapy with other nanomedicines for various cancer therapies, and revealed that HBO therapy could significantly boost antitumor efficacy of nanomedicine-mediated photodynamic therapy and photothermal therapy in different kinds of tumors, including hepatocellular carcinoma, breast cancer, and gliomas. Our results implicate that HBO therapy might be a universal strategy to boost therapeutic efficacy of nanomedicine against hypoxic solid malignancies."

Clinical • Journal • Breast Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor

Long-Term Dormant Cells in Acute Myeloid Leukemia Patient-Derived Xenografts Display Reversible Treatment Resistance, but Are Not Enriched for Leukemia-Initiating Cells (ASH 2018) - "To determine whether dormant and cycling cells differ in their drug response, mice were injected with CFSE labeled PDX cells and treated from day 7 to 9 with Cytarabine and with DaunoXome on day 7. As dormant and cycling cells contain similar LIC frequencies, our data provide evidence that dormancy and stemness are independent traits of AML. In conclusion, dormancy as well as the reversibility of the dormant phenotype are important biological characteristics of AML that need to be considered when designing treatment strategies that aim to eradicate drug resistant LIC."

Clinical • Acute Myelogenous Leukemia • Biosimilar • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation

Long-Term Dormancy is Reversible in Patients’ AML Cells Growing in Mice (ISAL 2019) - "To determine whether LRC and nLRC differ in their drug response, mice were injected with CFSE labeled PDX cells, received 3 doses of cytarabine and one dose of DaunoXome (days 7-9), and treatment response was analyzed at day 10. AML PDX contain a rare subpopulation of dormant and treatment resistant cells. Dormancy as well as reversibility of the dormant phenotype are important biological characteristics of AML cells that need to be considered when designing treatment strategies that aim to eradicate drug resistant AML cells. Conflict of interest: none"

Isatuximab in Combination with Chemotherapy in Pediatric Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia (clinicaltrialsregister.eu) - P2; N=128; Sponsor: Sanofi-aventis recherche & developpement

Clinical • Combination therapy • New P2 trial