- |||||||||| Clinical, P2 data, Journal: Emerging drugs for the treatment of myelofibrosis: phase II & III clinical trials. (Pubmed Central) - Jan 27, 2022
Ruxolitinib and fedratinib are approved JAK2 inhibitors that have produced meaningful benefits in terms of spleen reduction and symptom improvement, but there remain several unmet needs...Specifically, we cover novel JAK inhibitors (momelotinib and pacritinib), and agents that target bromodomain and extra-terminal domain (pelabresib), the antiapoptotic proteins BCL-2/BCL-xL (navitoclax), MDM2 (navtemadlin), phosphatidylinositol 3-kinase (parsaclisib), or telomerase (imetelstat)...Future evaluation of agents must be judged on their potential to modify disease progression, which current JAK2 inhibitors lack. Combination therapy, possibly with an immunotherapeutic agent might serve as key components of future myelofibrosis treatment options.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Preclinical, Journal: Characterization of In Vitro G-Quadruplex Formation of Imetelstat Telomerase Inhibitor. (Pubmed Central) - Jan 14, 2022
We demonstrated that different structural elements, such as the 5'-palmitoyl linker and the thio-phosphoramidate backbone, critically contribute to G-quadruplex stability. Experiments further showed that G-quadruplex formation does not hamper binding to the hTR oligonucleotide sequence in vitro.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Clinical, Journal, Real-world evidence: Favorable overall survival with imetelstat in relapsed/refractory myelofibrosis patients compared with real-world data. (Pubmed Central) - Jan 14, 2022
Results of sensitivity analyses were consistent with the primary analysis. In conclusion, treatment with imetelstat was associated with longer overall survival compared to BAT (30 vs 12 months, respectively) in closely matched patients with MF after JAK inhibitor failure, warranting further evaluation of imetelstat in this poor-prognosis patient population.
- |||||||||| imetelstat (JNJ-63935937) / Geron, pelabresib (CPI-0610) / MorphoSys, navitoclax (ABT 263) / AbbVie
Journal: New Therapies in Development for Myelofibrosis. (Pubmed Central) - Dec 25, 2021
In conclusion, treatment with imetelstat was associated with longer overall survival compared to BAT (30 vs 12 months, respectively) in closely matched patients with MF after JAK inhibitor failure, warranting further evaluation of imetelstat in this poor-prognosis patient population. No abstract available
- |||||||||| azacitidine / Generic mfg.
Journal: Advances in myelodysplastic syndrome. (Pubmed Central) - Nov 29, 2021
We also provide commentary on the future of therapeutic development in myelofibrosis. Better diagnosis and prognostic stratification may allow a more precise and personalized treatment of MDS with novel agent combinations leading to improved therapeutic algorithms.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Imetelstat Significantly Reduces Leukemia Stem Cells in Patient-Derived Xenograft Models of Pediatric AML (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5030;
These results were corroborated in vivo in two distinct PDX models which showed reduced LSC population and increased median survival in mice with imetelstat treatment. Combining imetelstat with chemotherapy or azacitidine further enhanced activity against LSCs, suggesting imetelstat could represent an effective therapeutic strategy for pediatric AML.
- |||||||||| imetelstat (JNJ-63935937) / Geron
A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat Versus Best Available Therapy (BAT) in Patients with Intermediate-2 (Int-2) or High-Risk Myelofibrosis (MF) Refractory to Janus Kinase Inhibitor (JAKi) (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3077;
P3
The JAKi ruxolitinib and fedratinib are the only FDA approved treatment options for MF...Pts will be randomized to receive imetelstat 9.4 mg/kg IV every 21 days or investigator selected BAT (including hydroxyurea, thalidomide, interferon, danazol, hypomethylating agents, chemotherapy, or other non-JAKi containing therapy as appropriate)...Approximately 180 sites are planned in North and South America, Europe, Middle East, Australia, and Asia. The study is open for enrollment.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Mutant TP53 prevents Telomere Shortening in Acute Myeloid Leukemia (GWCC - Thomas Murphy Ballroom 3-4, Level 5) - Nov 5, 2021 - Abstract #ASH2021ASH_1744;
Availability of therapies targeting the telomere machinery (Imetelstat) may offer an opportunity for personalized therapy beyond MPN, its current indication. It remains to be tested whether long TL associated with TP53 mutations can serve as marker of sensitivity or resistance to these agents.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Clinical, Journal: Dynamics of mutations in patients with essential thrombocythemia treated with imetelstat. (Pubmed Central) - Oct 29, 2021
P2
Moreover, imetelstat demonstrates potential to inhibit efficiently co-incident mutations occurring in neoplastic clones in patients with essential thrombocythemia. (ClinicalTrials.gov number, NCT01243073 N Engl J Med 2015; 373:920-928, DOI: 10.1056/NEJMoa1503479.).
- |||||||||| [VIRTUAL] NOVEL APPROACHES IN LOW-RISK MDS () - Sep 26, 2021 - Abstract #MDS2021MDS_292;
Imetelstat, a telomerase inhibitor, is currently in phase 2/3 study in RBC transfusion–dependent and ESA-relapsed or refractory low-risk MDS patients, with encouraging preliminary results. Finally, thrombopoietin-receptor agonists, such as romiplostim or eltrombopag, are not formally approved for patients with MDS but may be a treatment option for thrombocytopenia in patients with blasts <5%.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Imetelstat gang (Twitter) - Sep 15, 2021
- |||||||||| imetelstat (JNJ-63935937) / Geron
Imetelstat champ (Twitter) - Sep 10, 2021
- |||||||||| imetelstat (JNJ-63935937) / Geron
Imetelstat??? (Twitter) - Sep 9, 2021
- |||||||||| Review, Journal: Current and emerging strategies for management of myelodysplastic syndromes. (Pubmed Central) - Sep 5, 2021
Targeted therapies approved for acute myeloid leukemia treatment, such as isocitrate dehdyrogenase inhibitors and venetoclax, are also being studied for use in MDS. In this review, we provide a brief overview of pathogenesis and current treatment strategies in MDS followed by a discussion of newer agents that are under clinical investigation.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Imetelstat (Twitter) - Aug 6, 2021
- |||||||||| imetelstat (JNJ-63935937) / Geron
Imetelstat (Twitter) - Aug 6, 2021
- |||||||||| imetelstat (JNJ-63935937) / Geron
Biomarker, Journal: Targeting Telomere Biology in Acute Lymphoblastic Leukemia. (Pubmed Central) - Jul 21, 2021
TL and TA might complement established markers for the identification of patients with high-risk ALL. Moreover, TA seems to be an effective therapeutic target; hence, telomerase inhibitors, such as imetelstat, may augment standard ALL treatment.
- |||||||||| Review, Journal: Novel therapeutics in myeloproliferative neoplasms. (Pubmed Central) - Jun 8, 2021
Despite improving biological understanding of these complex clonal hematopoietic stem/progenitor cell neoplasms, none of the currently available therapies appear to modify the proclivity of the disease per se, thereby remaining an urgent unmet clinical need and an ongoing area of intense clinical investigation. This review will highlight the evolving targeted therapeutic agents that are in early- and late-stage MPN clinical development.
- |||||||||| imetelstat (JNJ-63935937) / Geron
Clinical, Journal: Developing strategies to reduce the duration of therapy for patients with myeloproliferative neoplasms. (Pubmed Central) - Jun 5, 2021
The experimental drug Imetelstat is a promising drug that has been reported to prolong survival in very high risk myelofobrosis patients after a limited period of time of administration. New experimental drugs and drug combinations that target the malignant clone and/or microenviromental abnormalities have the potential to eliminate MRD, which might allow for drug holidays and reduction in the duration of therapy.
- |||||||||| imetelstat (JNJ-63935937) / Geron, Jakafi oral (ruxolitinib) / Novartis, Incyte
Journal, Combination therapy: Novel and combination therapies for polycythemia vera and essential thrombocythemia: the dawn of a new era. (Pubmed Central) - Jun 5, 2021
A discussion of recent clinical trials on interferon and ruxolitinib in ET and PV patients is provided followed by an outline of the future challenges in the field particularly for novel therapeutics and an increasingly individualized, molecularly driven approach to treatment selection...While hydroxyurea remains the first-line treatment for cytoreduction in most high-risk ET and PV patients, the disease-modifying potential of IFN is promising and could make it a preferred option for selected patients. Advances in molecular testing will enable a more individualized approach to prognostication and treatment selection.
- |||||||||| [VIRTUAL] Potential New Therapeutic Approaches for Myelofibrosis () - May 20, 2021 - Abstract #SOHO2021SOHO_158;
Targeting the p53-HDM2 Axis KRT-232 is a first-in-class, potent, bioavailable inhibitor of HDM2 (key negative regulator of p53) that was assessed in a phase 2 study (KRT-232-101) and showed promising clinical efficacy and tolerability in TP53-wild type patients with MF who failed ruxolitinib treatment.17 A randomized phase 3 trial comparing KRT-232 (240 mg on days 1–7/28-day cycle) to BAT in MF patients refractory /resistant to JAK inhibitors has been launched...In the phase 2 study IMbark, the higher dose of imetelstat (9.4 mg/ kg) yielded a median overall survival of 29.9 months in patients with intermediate-2 or high-risk MF relapsed/refractory to JAK inhibitors.18 In light of the aforementioned promising result, a pivotal international phase 3 trial (IMpactMF) was launched to evaluate the survival advantage – an unprecedented trial endpoint for investigational MF medications – that imetelstat may confer to JAK-inhibitor-refractory MF patients.19 Conclusions The era of JAK1/2 inhibitor monotherapies in MF has ushered the way to the clinical development of a suite of promising novel medications spanning various biological mechanisms (for example, inhibitors of BET, HDM2, BCL-2/ BCL-XL, and telomerase, among others). Several highly promising candidates are currently evaluated in regulatory phase 3 clinical trials in the frontline and second line settings; these studies may lead to approval of novel medications that will significantly improve the current MF treatment paradigm.
- |||||||||| imetelstat (JNJ-63935937) / Geron, Revlimid (lenalidomide) / BMS, Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] IMETELSTAT DEMONSTRATES AN ACCEPTABLE SAFETY PROFILE IN MYELOID MALIGNANCIES () - May 13, 2021 - Abstract #EHA2021EHA_1864;
Methods These safety analyses focus on MYF2001 study pts randomized to imetelsat 9.4 mg/kg IV q 3 weeks (wks) (N=59) as of 7 Feb 2020 and the Phase 2 of the MDS3001 study in LR/Int-1 non-del(5q) transfusion dependent ESA R/R MDS pts, all lenalidomide and hypomethylating agent-naïve (N=38), who received 7.5 mg/kg IV every 4 wks as of 21 Oct 2020...Differences in disease pathology (proliferation vs dysplasia) could account for the differences in toxicity profiles in MF vs MDS pts. Ongoing Phase 3 studies in MF and MDS will confirm the safety profile of imetelstat in a controlled setting.
- |||||||||| imetelstat (JNJ-63935937) / Geron, BIBR1532 / Boehringer Ingelheim
Review, Journal: Telomerase: key regulator of inflammation and cancer. (Pubmed Central) - Mar 30, 2021
Despite significant effort invested in developing telomerase-targeted therapeutics, devising efficacious cancer-specific telomerase/TERT inhibitors remains an uphill task. The latest discoveries of the telomere-independent functionalities of telomerase in inflammation and cancer can help illuminate the path of developing specific anti-telomerase/TERT therapeutics against cancer cells.
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