Rytelo (imetelstat) / Geron - LARVOL DELTA

Efficacy and safety of imetelstat in transfusion-dependent lower-risk myelodysplastic syndromes: A systematic review and meta-analysis. (ASCO 2025) - "This meta-analysis provides evidence for the efficacy of imetelstat in achieving transfusion independence in heavily transfused patients with LR-MDS and limited treatment options. Further studies are needed to confirm its efficacy and safety."

Retrospective data • Review • Acute Myelogenous Leukemia • Anemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia

Outcomes with imetelstat in myelofibrosis: A systematic review and meta-analysis. (ASCO 2025) - "This meta-analysis shows good efficacy of Imetelstat in MF patients with an acceptable safety profile. However, results should be interpreted cautiously considering the small sample size and large clinical trials are needed to consolidate these findings."

Retrospective data • Review • Anemia • Essential Thrombocythemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Polycythemia Vera • Thrombocytopenia • Thrombocytosis • CALR • JAK2

IMproveMF update: Phase 1/1B trial of imetelstat (IME)+ruxolitinib (RUX) in patients (pts) with intermediate (INT)-1, INT-2, or high-risk (HR) myelofibrosis (MF). (ASCO 2025) - P1, P2 | "In part 1 of IMproveMF, no DLTs were observed and the RP2D dose of 9.4 mg/kg IME was determined. AEs were consistent with those observed in other IME clinical trials, and preliminary efficacy was positive, demonstrating the potential of IME+RUX in this pt population with high unmet needs. Part 2 of this trial is ongoing across the US at 6 sites."

Clinical • P1 data • Anemia • Fatigue • Hematological Disorders • Infectious Disease • Leukopenia • Myelofibrosis • Neutropenia • Pain • Pneumonia • Respiratory Diseases

Effect of prior treatment (tx) on the clinical activity of imetelstat (IME) in transfusion-dependent (TD) patients (pts) with erythropoiesis-stimulating agent (ESA), relapsed or refractory (R/R)/ineligible lower-risk myelodysplastic syndromes (LR-MDS). (ASCO 2025) - P2/3 | "Prior lenalidomide (LEN) and prior hypomethylating agent (HMA) use were exclusion criteria in phase 3 only. In this analysis, pooled data from IME-treated pts (phase 2, phase 3, and QTc substudy) were analyzed by prior tx: ± ESA, luspatercept (LUSP), LEN, and HMA; pts may have received >1 prior tx... Pts who were ESA ineligible or who had prior tx with LUSP, LEN, or HMA, and were largely high TB, in IMerge experienced clinical benefit from IME tx, though the number of pts was small. Given the limited efficacy data available in later lines of tx for LR-MDS, these results have important clinical implications, suggesting that IME has clinical activity regardless of prior txs."

Clinical • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

IMpactMF, randomized, open-label, phase 3 trial of imetelstat (IME) versus best available therapy (BAT) in patients (pts) with intermediate-2 (INT-2) or high-risk (HR) myelofibrosis (MF) relapsed or refractory (R/R) to Janus kinase inhibitors (JAKi). (ASCO 2025) - P2, P3 | "Randomization is to IME sodium 9.4 mg/kg (8.9 mg/kg active dose) intravenously q3w or investigator-selected BAT (eg, hypomethylating agents, hydroxyurea, interferon, thalidomide, danazol, chemotherapy, or other non–JAKi-containing therapy, but not hematopoietic stem cell transplantation or splenectomy). As of December 2024, 172 sites in North and South America, Europe, Middle East, Australia, and Asia have enrolled ≈75% of pts. The planned interim analysis (when ≈35% of pts planned to be enrolled have died) is expected in early 2026 and final analysis is expected in early 2027."

Clinical • P3 data • Anemia • Bone Marrow Transplantation • Cardiovascular • Fibrosis • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Myelodysplastic Syndrome • Myelofibrosis • Neutropenia • Thrombocytopenia

Navigating the dynamic landscape of lower-risk MDS: Advances and emerging insights. (PubMed, Blood Rev) - "With the exception of lenalidomide which was approved in 2005 in USA, therapeutic advancements in LR-MDS have stalled for almost 15 years...This evolution has led to a number of approvals, including luspatercept approved in 2020, and imetelstat, which was approved in 2024 in USA. As the therapeutic landscape of LR-MDS continues to evolve, there is growing optimism that these recent milestones will pave the way for further advancements and improved patient outcomes. Next set of studies should focus on the optimal sequencing and combinations of existing agents, as well as moving forward novel effective agents."

Journal • Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation

IMPROVEMF UPDATE: PHASE 1/1B TRIAL OF IMETELSTAT (IME)+RUXOLITINIB (RUX) IN PATIENTS WITH INTERMEDIATE (INT)-1, INT-2, OR HIGH-RISK (HR) MYELOFIBROSIS (MF) (EHA 2025) - P1, P2 | "In part 1 of IMproveMF, no DLTs were observed and the RP2D dose of 9.4 mg/kg IME was determined. AEs were consistent with those observed in other IME clinical trials, and preliminary efficacy was positive, demonstrating the potential of IME+RUX in this pt population with high unmet needs. Part 2 of this trial is ongoing across the United States at 6 sites."

Clinical • P1 data • Anemia • Fatigue • Hematological Disorders • Infectious Disease • Leukopenia • Myelofibrosis • Neutropenia • Pain • Pneumonia • Respiratory Diseases

IMproveMF: A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Imetelstat in Combination With Ruxolitinib in Participants With Myelofibrosis (clinicaltrials.gov) - P1 | N=51 | Recruiting | Sponsor: Geron Corporation | Trial completion date: Aug 2027 ➔ Aug 2028 | Trial primary completion date: Feb 2026 ➔ Feb 2027

Trial completion date • Trial primary completion date • Myelofibrosis

New pooled, post-hoc analyses expand on the pivotal IMerge results across challenging LR-MDS subpopulations (Geron Corporation Press Release) - "Analysis of patients with ring sideroblast negative (RS-) disease, showing that these difficult-to-treat patients appeared to experience clinical benefit with RYTELO, including ≥8-week, ≥24-week and ≥1-year red blood cell transfusion independence (RBC-TI), duration of RBC-TI, and hemoglobin rise in patients who achieved RBC-TI, consistent with prior findings from the overall Phase 3 IMerge population; Analysis showing clinical benefit with RYTELO regardless of baseline serum erythropoietin (sEPO) level, supporting the use of RYTELO in the frontline setting for LR-MDS patients ineligible for erythropoiesis-stimulating agents (ESAs), and in the second-line setting after ESAs regardless of sEPO; Analysis showing clinical benefit with RYTELO in ESA-ineligible or relapsed/refractory patients regardless of prior treatment with luspatercept or lenalidomide."

Retrospective data • Myelodysplastic Syndrome

Geron Announces Presentations at ASCO and EHA Underscoring RYTELO (imetelstat) Efficacy and Safety Across Range of LR-MDS Patients, and Showcasing Momentum of Myelofibrosis Program (Geron Corporation Press Release) - "Geron Corporatio...announced presentations on RYTELO (imetelstat) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) 2025 Congress. Together, the presentations reinforce the potential benefits of the first-in-class oligonucleotide telomerase inhibitor RYTELO for a range of patients with lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia and showcase the progress Geron is making with the ongoing IMpactMF and IMproveMF trials of imetelstat in myelofibrosis (MF)."

Clinical data • Trial status • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis

Patient-centric outcome measures offering deeper insight on RYTELO impact in new post-hoc analyses from Phase 3 IMerge trial (Geron Corporation Press Release) - P2/3 | N=289 | IMerge (NCT02598661) | Sponsor: Geron Corporation | "Analysis showing that certain RYTELO-treated patients experienced sustained improvements in health-related quality-of-life (QOL) compared with placebo, as measured by certain categories in the patient-reported QOL in Myelodysplasia Scale (QUALMS) instrument; Exploratory analysis suggesting that certain patients treated with RYTELO experienced a longer mean duration of time without transfusion reliance or relapse (TWiTR), compared with placebo."

P2/3 data • Myelodysplastic Syndrome

Rytelo: “The committee confirmed that all issues previously identified in this application had been addressed”; Myelodysplastic syndrome (European Medicines Agency) - CHMP Final Minutes of the meeting on 9- 12 Dec 2024: “The committee adopted a positive opinion recommending the granting of a marketing authorisation by consensus together with the CHMP assessment report and translation timetable”

CHMP • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Little to show for much effort and investment: An industry perspective on MDS drug development (MDS 2025) - "Randomized studies incorporated lenalidomide, vorinostat, entinostat (MS-275), durvalumab, valproic acid, idarubicin, eltrombopag, pevonedistat (MLN4924), eprenetapopt (APR-246), sabatolimab (MBG453), magrolimab (Hu5F9-G4), or tamibarotene (SY-1425)...While the approval of luspatercept and imetelstat for lower-risk patients provides a glimmer of hope, this track record of failure in higher-risk MDS is enough to make a prudent investor or senior pharmaceutical executive think twice before committing further resources to development in this difficult group of diseases...Nor is it because the existing therapies are so good that they're hard to beat, although the practice of giving a few cycles of azacitidine or decitabine in local clinics before referring a patient to a trial center has been an unfortunate barrier to accrual...In this session I will discuss some potential fixes for a few of these problems. But solutions to other barriers are less clear, and will require..."

Acute Myelogenous Leukemia • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • FLT3 • TP53

Transfusion Independence Corresponds With Survival in Patients With Lower-Risk Myelodysplastic Syndrome: Real-World Evidence From United States Insurance Claims. (PubMed, Clin Lymphoma Myeloma Leuk) - "Results suggest RBC-TD may be a modifiable factor corresponding to clinical outcomes in LR-MDS, further supporting RBC-TI as a primary endpoint in clinical studies."

HEOR • Journal • Real-world evidence • Reimbursement • US reimbursement • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

IMPACTMF, RANDOMIZED, OPEN-LABEL, PHASE 3 TRIAL OF IMETELSTAT VERSUS BEST AVAILABLE THERAPY IN PATIENTS WITH INTERMEDIATE-2 OR HIGH-RISK MYELOFIBROSIS RELAPSED OR REFRACTORY TO JANUS KINASE INHIBITORS (EHA 2025) - P2, P3 | "Randomization is to IME sodium 9.4 mg/kg (8.9 mg/kg active dose) intravenously q3w or investigator-selected best available therapy (BAT; eg, hypomethylating agents, hydroxyurea, interferon, thalidomide, danazol, chemotherapy, or other non–JAKi-containing therapy, but not hematopoietic stem cell transplantation or splenectomy). Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Annual Meeting."

Clinical • P3 data • Anemia • Bone Marrow Transplantation • Cardiovascular • Fibrosis • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Myelodysplastic Syndrome • Myelofibrosis • Neutropenia • Thrombocytopenia

EFFICACY AND OUTCOMES OF NOVEL THERAPEUTIC AGENTS AS MONOTHERAPY OR IN COMBINATION WITH CONVENTIONAL THERAPY IN MYELODYSPLASTIC SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2025) - "Newer agents included Rigosertib (41%, n=312/770), Imetelstat (15%, n=118/770), Pembrolizumab (8%, n=65/770), Enasidenib (9%, n=67/770), and Sabatolimab (7%, n=53/770) Ivosidenib (6%, 45/770), Elritercept 2%, n=15 /770), Pevonedistat (3%, 21/770), Emavusertib (2%, 15/770), Atezolizumab (6%, 46/770), and Olutasidenib (2%, n=13/770). The most commonly used conventional agent was azacitidine (19%, n= 147/770)... This study highlights promising results with the investigational agents for MDS. However, large studies with more power are needed to strengthen our understanding of these investigational agents in MDS patients."

Combination therapy • Monotherapy • Retrospective data • Review • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia

TRIAL IN PROGRESS: MIDAS - A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF MOMELOTINIB IN PATIENTS WITH ANEMIA DUE TO LOWER-RISK MYELODYSPLASTIC SYNDROMES (EHA 2025) - P2 | "First-line treatments include erythropoiesis-stimulating agents (ESAs) or luspatercept, and imetelstat is a second-line option following ESAs...Patients may enroll regardless of ring sideroblast status, while those with del5q cytogenetic abnormalities are ineligible regardless of prior lenalidomide exposure.In part 1 (Figure), 40 patients will be stratified by baseline transfusion burden (≤6 vs >6 units in 8 weeks) and randomized 1:1 to 1 of 2 momelotinib dose levels to establish the RP2D, at which up to 40 patients will be enrolled in part 2... This will be the first clinical study of momelotinib in patients with LR-MDS and anemia. Part 1 enrollment is planned to begin in April 2025."

Clinical • P2 data • Anemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR1 • IRAK1 • JAK1 • JAK2

CHARACTERIZATION AND MANAGEMENT OF TRANSIENT CYTOPENIAS ASSOCIATED WITH IMETELSTAT (IME) IN LOWER-RISK MYELODYSPLASTIC SYNDROMES (LR-MDS) FROM THE IMERGE TRIAL (EHA 2025) - P2/3 | "In this post-hoc analysis of pooled IME-treated pts from the IMerge study, grade 3/4 neutropenia and thrombocytopenia events largely occurred early in treatment, had a short duration, and did not lead to any significant clinical consequences. Neutropenia and thrombocytopenia with IME treatment were generally manageable with cycle delays and dose reductions and did not lead to treatment discontinuation in most pts. Sponsor: Geron Corporation."

Acute Myelogenous Leukemia • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia

OUTCOMES OF IMETELSTAT THERAPY IN PATIENTS WITH RING SIDEROBLAST-NEGATIVE LOWER-RISK MYELODYSPLASTIC SYNDROMES FROM THE POOLED IMERGE STUDY POPULATIONS (EHA 2025) - P2/3 | "Current treatment options are limited in number and efficacy, particularly for patients (pts) who are either ineligible for erythropoiesis-stimulating agents (ESAs) or whose disease is relapsed or refractory to ESAs.First-line luspatercept demonstrated differential efficacy in RS positive compared with RS-neg disease; a benefit in RS positive disease was also observed with luspatercept in the second line compared with placebo (PBO). In this post hoc analysis, pts with RS-neg LR-MDS who were relapsed or refractory to or ineligible for ESAs experienced clinical benefit from IME treatment. These results were consistent with prior findings and further support that IME has clinical activity in pts with difficult-to-treat RS-neg disease with a high transfusion burden, and with different clinical subtypes of MDS with no available therapy options. Sponsor: Geron Corporation."

Clinical • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

HEALTH-RELATED QUALITY OF LIFE OUTCOMES IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES TREATED WITH IMETELSTAT IN THE IMERGE TRIAL (EHA 2025) - P2/3 | "In this post hoc analysis, IME-treated pts appeared to experience sustained meaningful improvements across QUALMS domains. Improvements in the physical burden domain were observed in more pts treated with IME versus PBO. A significantly higher proportion of TI responders experienced sustained meaningful improvement in QUALMS-P scores than non-responders in the IME group."

Clinical • HEOR • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Pulmonary Disease

OUTCOMES WITH IMETELSTAT BY SERUM ERYTHROPOIETIN LEVELS IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES WHO WERE TREATMENT NAIVE OR WHO HAD PRIOR TREATMENT WITH ERYTHROPOIESIS-STIMULATING AGENTS (EHA 2025) - P2/3 | "In this post hoc pooled analysis, patients with LR-MDS who were treatment naive and had high sEPO at baseline experienced clinical benefit with imetelstat. Additionally, patients who had prior ESA therapy experienced clinical benefit with imetelstat regardless of baseline sEPO levels, including those with sEPO >500 mU/mL. Together, these findings support the use of imetelstat in the frontline setting in patients with LR-MDS who are ineligible for ESAs, and further support use in these patients after ESA therapy regardless of baseline sEPO."

Clinical • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

INCREASED DURATION OF TIME WITHOUT TRANSFUSION RELIANCE FOR PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES TREATED WITH IMETELSTAT VERSUS PLACEBO IN THE IMERGE TRIAL (EHA 2025) - P2/3 | "This post hoc TWiTR analysis showed that patients with LR-MDS in the IME arm had a longer duration of time without transfusion reliance or relapse compared with PBO. Thus, the ability of IME to lessen TD was clinically meaningful to patients, given the negative association between TD and QOL. Sponsor: Geron Corporation."

Clinical • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Imetelstat (MDS 2025) - No abstract available

Hematological Malignancies • Myelodysplastic Syndrome

TELOMERE CONTENT IN MYELOID NEOPLASIA COULD INFORM ON DIFFERENTIAL SENSITIVITY TO TELOMERASE INHIBITORS (MDS 2025) - "Abstract Background and Aims Recent FDA approval of telomerase inhibitor imetelstat, inspired our inquiry whether telomere content (TC) constitutes a biomarker for this drug in MDS.MethodsWe adopted WGS-based pipelines to measure TC in MDS and related neoplasias (1432) and 163 non-malignant controls including PNH/AA [n=102], polyclonal B lymphocytosis (n=50) and healthy subjects [n=11]).ResultsWe observed a general decrease in TC in MDS/AML irrespective of age...Functional studies, including singletons telomer composition, C-circle analysis and transcriptome-based scores to assess telomerase activity (EXTENDScore) showed that TP53 mutations maintain telomere elongation activity. ConclusionsCurrently ongoing studies aim to determine whether higher/lower TC content is predictive of imelestat responsiveness."

Acute Myelogenous Leukemia • Hematological Malignancies • Oncology • ETV6 • FLT3 • JAK2 • KRAS • NPM1 • NRAS • SF3B1 • SRSF2 • TP53

Critical review on treatment guidelines (MDS 2025) - "Luspatercept: Pros: Effective in reducing transfusion burden, including in ESA-resistant patients; Higher and durable response rates compared to ESAs; Novel mechanism...Lenalidomide: The advantages are high erythroid efficacy (anemia of del5q) and high cytogenetic response rate as well as oral administration and suggested delay in transfusion needs...Imetelstat: Advantages: Reduction in transfusion burden; Novel mechanism of action; Efficacy in ESA-refractory/ineligible patient...Cons: Lack of definitive prospective data; Side Effects; Burden of therapy; and the cost. In summary, prior to treatment for LR-MDS the points that should be considered include the particular treatment efficacy vs side effects and complication, the availability and cost, the particular type of MDS and other patients' characteristics (comorbidities) as well as the patient preferences."

Review • Hematological Malignancies • Myelodysplastic Syndrome • TP53