Publications by authors named "Faye Feller"
Most cancers and neoplastic progenitor cells have elevated telomerase activity and preservation of telomeres that promote cellular immortality, making telomerase a rational target for the treatment of cancer. Imetelstat is a first-in-class, 13-mer oligonucleotide that binds with high affinity to the template region of the RNA component of human telomerase and acts as a competitive inhibitor of human telomerase enzymatic activity. Pharmacokinetics, pharmacodynamics, exposure-response analyses, efficacy, and safety of imetelstat have been evaluated in vitro, in vivo, and clinically in solid tumor and hematologic malignancies, including lower-risk myelodysplastic syndromes (LR-MDS) and myeloproliferative neoplasms.
View Article and Find Full Text PDFPopulation pharmacokinetics of imetelstat, a first-in-class oligonucleotide telomerase inhibitor.
CPT Pharmacometrics Syst Pharmacol
July 2024
Article Synopsis
- * A mixed-effects model was created to analyze how different factors like demographics and health conditions affect the drug's pharmacokinetics using data from 424 patients across seven clinical trials.
- * The final model found that factors such as sex, disease type, and dosage impact drug clearance and volume in the body, but generally suggests that body-weight-based dosing is appropriate without needing individual dose adjustments for most patients.
Article Synopsis
- The study focuses on patients with lower-risk myelodysplastic syndromes (LR-MDS) who depend on red blood cell transfusions and are either not responding to current treatments or are ineligible for them, particularly erythropoiesis-stimulating agents (ESAs).
- It involves a phase 3 clinical trial comparing the effectiveness of imetelstat (a telomerase inhibitor) to a placebo in achieving red blood cell transfusion independence, involving 178 participants across various countries.
- The primary goal was to measure the percentage of patients who went at least 8 weeks without needing transfusions after starting treatment, with results from this study expected to provide insights into a potential new treatment
Article Synopsis
- * The phase III trial, IMpactMF, will compare imetelstat to the best available therapies (excluding JAK inhibitors) in these refractory MF patients.
- * The trial will administer imetelstat via IV every 21 days, focusing on overall survival as the main goal, while also examining additional effects such as symptom relief, spleen size, and safety.
Acute myeloid leukemia (AML) is characterized by poor clinical outcomes due to high rates of relapse following standard-of-care induction chemotherapy. While many pathogenic drivers have been described in AML, our understanding of the molecular mechanisms mediating chemotherapy resistance remains poor. Therefore, we sought to identify resistance genes to induction therapy in AML and elucidated ALOX5 as a novel mediator of resistance to anthracycline-based therapy.
View Article and Find Full Text PDFArticle Synopsis
- The MYF2001 trial found that the JAK inhibitor-relapsed/refractory patients with intermediate-2 or high-risk myelofibrosis (MF) treated with the drug imetelstat (9.4 mg/kg every 3 weeks) had a median overall survival of 29.9 months.
- The study also involved comparing real-world data from patients who stopped using ruxolitinib and received the best available therapy (BAT) using matching criteria from the MYF2001 trial.
- The analysis revealed that patients treated with imetelstat had a significantly lower risk of death compared to those receiving BAT, with a notable survival difference (30 months for imetelstat vs. 12
Article Synopsis
- Myelofibrosis patients who don't respond to JAK inhibitors have a poor survival rate of about 13-16 months; a phase II study was conducted to evaluate the telomerase inhibitor imetelstat in these patients.
- In this study, patients received either 9.4 mg/kg or 4.7 mg/kg of imetelstat to assess responses in spleen size reduction and symptom improvement, with results showing better outcomes for the higher dose.
- The higher dose (9.4 mg/kg) led to a median overall survival of 29.9 months and significant benefits in symptom relief, despite common side effects like reversible cytopenias, prompting further phase III studies.
Article Synopsis
- - This study focuses on using Imetelstat, a drug that inhibits telomerase, for treating patients with lower-risk myelodysplastic syndromes (MDS) who depend on red blood cell (RBC) transfusions and have not responded well to previous treatments.
- - In a phase II/III trial, 57 patients were treated, showing 37% had RBC transfusion independence (TI) after 8 weeks and 23% after 24 weeks, with median TI lasting about 65 weeks overall, and even longer in a specific subgroup.
- - The findings suggest Imetelstat not only helps reduce reliance on transfusions but also appears to impact the malignant cells associated with the disease, with
Drug-induced thrombocytopenia often results from dysregulation of normal megakaryocytopoiesis. In this study, we investigated the mechanisms responsible for thrombocytopenia associated with the use of Panobinostat (LBH589), a histone deacetylase inhibitor with promising anti-cancer activities. The effects of LBH589 were tested on the cellular and molecular aspects of megakaryocytopoiesis by utilizing an ex vivo system in which mature megakaryocytes (MK) and platelets were generated from human primary CD34(+) cells.
View Article and Find Full Text PDF