Geron Announces New Data to be Presented at Upcoming ASH Annual Meeting Highlighting the Potential of RYTELO™ (imetelstat) in Myeloid Hematologic Malignancies
Geron (GERN) announced new data presentations for RYTELO™ (imetelstat) at the upcoming ASH Annual Meeting. Key highlights include analyses from the IMerge clinical trial showing imetelstat's clinical activity in lower-risk MDS patients with transfusion-dependent anemia, regardless of prior therapy. Early safety results from the Phase 1 IMproveMF study suggest potential tolerability of imetelstat combined with ruxolitinib in frontline myelofibrosis patients. The data will be presented through six abstracts at the 66th ASH Annual Meeting in December 2024.
Notable results include RBC-transfusion independence rates and hemoglobin improvements across different patient subgroups, with positive responses seen even in patients who received prior treatments like luspatercept, lenalidomide, and HMAs.
Geron (GERN) ha annunciato nuove presentazioni di dati per RYTELO™ (imetelstat) all'imminente Congresso Annuale dell'ASH. I punti salienti includono analisi trial clinico IMerge che mostrano l'attività clinica di imetelstat nei pazienti MDS a basso rischio con anemia da trasfusione, indipendentemente dalla terapia precedente. I primi risultati di sicurezza dello studio Phase 1 IMproveMF suggeriscono una potenziale tollerabilità di imetelstat combinato con ruxolitinib nei pazienti con mielofibrosi in prima linea. I dati saranno presentati attraverso sei abstract al 66° Congresso Annuale dell'ASH nel dicembre 2024.
I risultati notevoli includono tassi di indipendenza dalle trasfusioni di RBC e miglioramenti della emoglobina in diversi sottogruppi di pazienti, con risposte positive osservate anche nei pazienti che avevano ricevuto trattamenti precedenti come luspatercept, lenalidomide e HMAs.
Geron (GERN) anunció nuevas presentaciones de datos para RYTELO™ (imetelstat) en la próxima Reunión Anual de la ASH. Los aspectos más destacados incluyen análisis del ensayo clínico IMerge que muestran la actividad clínica de imetelstat en pacientes con MDS de bajo riesgo con anemia dependiente de transfusiones, independientemente de la terapia previa. Los primeros resultados de seguridad del estudio de Fase 1 IMproveMF sugieren una posible tolerabilidad de imetelstat combinado con ruxolitinib en pacientes con mielofibrosis en primera línea. Los datos se presentarán a través de seis resúmenes en la 66.ª Reunión Anual de la ASH en diciembre de 2024.
Los resultados destacados incluyen las tasas de independencia de transfusiones de RBC y mejoras en la hemoglobina en diferentes subgrupos de pacientes, con respuestas positivas observadas incluso en pacientes que recibieron tratamientos previos como luspatercept, lenalidomida y HMAs.
Geron (GERN)은 다가오는 ASH 연례 회의에서 RYTELO™ (imetelstat)에 대한 새로운 데이터 발표를 발표했습니다. 주요 내용은 IMerge 임상 시험의 분석으로, 이 임상시험은 이전 치료와 관계없이 수혈에 의존하는 저위험 MDS 환자에서 imetelstat의 임상 활성을 보여줍니다. Phase 1 IMproveMF 연구의 초기 안전성 결과는 일차성 골수섬유증 환자에서 ruxolitinib과 병합된 imetelstat의 잠재적인 내약성을 제안합니다. 이 데이터는 2024년 12월 66회 ASH 연례 회의에서 총 여섯 개의 초록을 통해 발표될 예정입니다.
주목할 만한 결과로는 RBC 수혈 독립 비율과 다양한 환자 하위 그룹에서의 헤모글로빈 개선이 포함되며, luspatercept, lenalidomide 및 HMAs와 같은 이전 치료를 받은 환자에서도 긍정적인 반응이 관찰되었습니다.
Geron (GERN) a annoncé de nouvelles présentations de données pour RYTELO™ (imetelstat) lors de la prochaine réunion annuelle de l'ASH. Les points forts incluent des analyses de l'essai clinique IMerge montrant l'activité clinique d'imetelstat chez les patients MDS à faible risque souffrant d'anémie dépendante des transfusions, quelle que soit la thérapie antérieure. Les premiers résultats de sécurité de l'
Les résultats notables comprennent les taux d'indépendance des transfusions de globules rouges et les améliorations de l'hémoglobine dans différents sous-groupes de patients, avec des réponses positives observées même chez les patients ayant reçu des traitements antérieurs tels que le luspatercept, le lenalidomide et les HMAs.
Geron (GERN) hat neue Datenpräsentationen für RYTELO™ (imetelstat) auf dem bevorstehenden ASH-Jahrestreffen angekündigt. Wichtige Highlights umfassen Analysen aus der IMerge-Studie, die die klinische Aktivität von imetelstat bei MDS-Patienten mit niedrigem Risiko und transfusionsabhängiger Anämie zeigen, unabhängig von vorheriger Therapie. Frühe Sicherheitsdaten aus der Phase-1-Studie IMproveMF deuten auf eine potenzielle Verträglichkeit von imetelstat in Kombination mit Ruxolitinib bei Patienten mit primärer Myelofibrose hin. Die Daten werden durch sechs Abstracts auf dem 66. ASH-Jahrestreffen im Dezember 2024 präsentiert.
Erwähnenswerte Ergebnisse umfassen die Raten der Unabhängigkeit von RBC-Transfusionen und Verbesserungen des Hämoglobins in verschiedenen Patientensubgruppen, wobei auch bei Patienten, die zuvor Behandlungen wie Luspatercept, Lenalidomid und HMAs erhalten hatten, positive Reaktionen zu beobachten waren.
- Clinical efficacy demonstrated in lower-risk MDS patients regardless of prior treatments
- Early safety results show potential tolerability of imetelstat-ruxolitinib combination therapy
- Sustained improvement in fatigue achieved in 55% of RS+ and 43% of RS- imetelstat-treated patients
- No dose limiting toxicities observed in IMproveMF trial
- Median duration of RBC-TI among responders was 52.6 weeks in QTc substudy
- 65% of patients experienced Grade 3/4 neutropenia in QTc substudy
- 49% of patients experienced Grade 3/4 thrombocytopenia in QTc substudy
- In IMpress trial, none of 23 treated patients reached primary endpoint visit
- 21 serious adverse events requiring hospitalizations reported in IMpress trial
Insights
The new data from IMerge clinical trials reveals significant findings for RYTELO (imetelstat) in treating blood cancers. The drug shows promising clinical activity in lower-risk MDS patients regardless of prior treatments, with
Key highlights include no cardiac repolarization concerns in the QTc substudy and meaningful improvements in patient-reported outcomes, particularly fatigue reduction. The IMproveMF trial's early safety results suggest good tolerability when combined with ruxolitinib for myelofibrosis treatment.
The data strengthens imetelstat's position as a potential treatment option, especially for patients who have failed other therapies. The positive patient outcomes and manageable safety profile could support broader adoption in clinical practice.
- New analyses from the IMerge clinical trial suggest that imetelstat demonstrates clinical activity in patients with lower-risk MDS with transfusion-dependent anemia regardless of prior therapy
- Early safety results from the dose escalation phase of the Phase 1 IMproveMF study suggest potential for the tolerability of combination therapy with imetelstat and ruxolitinib in a frontline myelofibrosis patient population
“We look forward to collaborating with our trial investigators to present meaningful data updates across the imetelstat pipeline, which we believe continue to highlight telomerase inhibition as an important and powerful approach to treating myeloid hematologic malignancies,” said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron.
Lower-Risk Myelodysplastic Syndromes (LR-MDS)
Abstract #352: “Effect of Prior Treatments on the Clinical Activity of Imetelstat in Transfusion-Dependent Patients with Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible Lower-Risk Myelodysplastic Syndromes”
Oral presentation on Saturday, December 7, 2024 at 4:45 p.m. PT by Uwe Platzbecker, M.D., Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, Leipzig University Hospital,
This abstract evaluates the effect of prior treatments on the clinical activity of imetelstat in patients with red blood cell (RBC) transfusion-dependent (TD) LR-MDS in an analysis of imetelstat-treated patients pooled from the IMerge Phase 2, Phase 3 and QTc studies (N=226). The results suggest that imetelstat demonstrates RBC-transfusion-related clinical activity and increases in hemoglobin in these patients regardless of prior therapies, although there are limited data on outcomes in later lines of treatment.
“There are very few treatment options today for patients with lower-risk MDS who have symptomatic anemia and are transfusion dependent, which often results in patients having to cycle through available therapies. By pooling data across the IMerge clinical trial, we sought to understand the potential of treatment with imetelstat for these patients regardless of their prior treatment. Although we have small numbers in some cases, these data have important clinical implications, suggesting that these patients experienced a RBC-transfusion related clinical benefit and improvements in hemoglobin with imetelstat regardless of their prior treatment,” said Dr. Platzbecker.
Therapy received prior to imetelstat treatment* |
≥8-week RBC-TI |
≥24-week RBC-TI |
RBC Transfusion Reduction of ≥4 U/8 weeks |
Hb Rise of ≥1.5 g/dL for ≥8 weeks |
HI-E (IWG 2018) |
ESA (n=204) |
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Luspatercept (n=35) |
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Lenalidomide (n=26) |
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HMA (n=22) |
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*Prior treatment was not mutually exclusive; patients may have received more than one prior therapy.
RBC-TI, red blood cell-transfusion independence; HI-E, hematologic improvement-erythroid; IWG, International Working Group; Hb, hemoglobin; ESA, erythropoiesis-stimulating agent; HMA, hypomethylating agent. |
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Additionally, in imetelstat-treated patients ineligible for ESA therapy (n=22) treated in the front-line,
Abstract #4590: “Initial Results from the QTc Substudy of the IMerge Phase 3 Trial Demonstrate Clinically Meaningful Efficacy, Manageable Safety, and Absence of Proarrhythmic Risk in Patients with Lower-Risk Myelodysplastic Syndromes Who Received Prior Therapies Beyond Erythropoiesis Stimulating Agents”
Poster presentation on Monday, December 9, 2024 from 6:00 p.m. - 8 p.m. PT by Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center
This abstract reports the first efficacy and safety results from the ventricular repolarization IMerge QTc substudy conducted per FDA guidance. This substudy differed from the IMerge Phase 3 trial in its crossover design, by allowing prior lenalidomide and HMA therapy besides ESAs and by allowing lower-risk MDS patients with the del(5q) mutation. As of the data cutoff on May 10, 2024, no clinically meaningful effects of imetelstat on cardiac repolarization or other ECG parameters were observed. In the 51 total imetelstat-treated patients (35 randomized and 16 crossover), the median treatment duration was 29.3 weeks and the median (
Abstract #3210: “Correlation of Patient-Reported Outcomes with Red Blood Cell Transfusion Reduction and Rise in Hemoglobin in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Trial”
Poster presentation on Sunday, December 8, 2024 from 6:00 p.m. - 8 p.m. PT by Mikkael Sekeres, MD, University of Miami Health System and Sylvester Comprehensive Cancer Center
This abstract reports on post-hoc analyses of the patient-reported outcome (PRO) population from the IMerge Phase 3 clinical trial (N=175; 118 treated with imetelstat and 57 treated with placebo). PROs were assessed with validated Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, Functional Assessment of Cancer Therapy-Anemia (FACT-An), and the Quality of Life in Myelodysplasia Scale (QUALMS) questionnaires. In the ring sideroblast positive (RS+) and RS negative (RS-) groups, respectively, sustained, meaningful improvement in fatigue was achieved by
“Low quality of life can be one of the most devastating and burdensome impacts of living with lower-risk MDS, particularly when patients are anemic and transfusion-dependent. The sustained improvement in fatigue and maintenance of quality of life and anemia symptoms with imetelstat shown in these post-hoc analyses are meaningful and very encouraging as we aim to improve outcomes for these patients,” Dr. Platzbecker continued.
Myelofibrosis (MF)
Abstract #998: “Trial Update from IMproveMF, an Ongoing, Open-Label, Dose-Escalation and -Expansion, Phase 1/1B Trial to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of the Novel Combination of Imetelstat with Ruxolitinib in Patients with Intermediate-1, Intermediate-2, or High-Risk Myelofibrosis (MF)”
Oral presentation on Monday, December 9, 2024 at 4:45 p.m. PT by John Mascarenhas, M.D., Professor of Medicine at the Icahn School of Medicine at Mount Sinai
This abstract reports the first safety results from the dose escalation Part 1 of the Phase 1/1B IMproveMF clinical trial, in which 13 patients were enrolled as of July 10, 2024. At least three patients received each dose level of imetelstat and doses of ruxolitinib were individualized per patient. No dose limiting toxicities (DLTs) were observed, and adverse events were consistent with those observed in other clinical trials of imetelstat. Imetelstat and ruxolitinib pharmacokinetic profiles in the combination study were similar to previous monotherapy studies. These early results show potential for the tolerability of the combination of imetelstat and ruxolitinib in this frontline MF patient population.
“These early results support the potential tolerability of imetelstat as a combination therapy and could have significant implications for future development efforts,” continued Dr. Feller.
Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes (HR-MDS)
Abstract #3222: “A Phase II Study Evaluating the Efficacy and Safety of Imetelstat in Patients with Advanced Myelodysplastic Neoplasms or AML Failing HMA-Based Therapy - Interim Analysis Results of the IMpress Study”
Poster presentation on Sunday, December 8, 2024 from 6:00 p.m. - 8 p.m. PT by Uwe Platzbecker, M.D.
This abstract, submitted by Geron collaborators, provides an interim analysis from the Phase 2 IMpress trial, led by the European Myelodysplastic Neoplasms Cooperative Group (EMSCO), which is evaluating imetelstat in patients with HR-MDS or AML, refractory, relapsing or intolerant to either azacitidine or decitabine, or venetoclax plus azacitidine. Between June and October 2023, 23 patients (6 HR-MDS, 17 AML) received at least one dose of imetelstat with an average of 2.8 doses administered per patient. In this first part of the trial, none of the 23 treated patients reached the primary endpoint visit, which was scheduled after 4 cycles of treatment. Sixteen of these 23 patients reached the preliminary disease assessment visit after two cycles of imetelstat; one patient showed a response in hematologic improvements in the erythroid and platelet lineages (HI-E and HI-P), 7 patients had stable disease and 8 patients had progressive disease. Short-term transient improvement in hematological values was observed in individual cases. In patients on the LR-MDS dosing schedule of every four weeks, imetelstat showed some antiproliferative effects, including a decline in blasts and leukocytes. Overall, no new safety signals occurred beyond those already known for imetelstat. A total of 30 serious adverse events (SAEs) occurred in 18 patients of which 21 SAEs required hospitalizations. Based on the observations in this first cohort, the protocol was amended to a more frequent dosing schedule for a second cohort of patients being enrolled and treated with this modified schedule starting in August 2024.
Abstract #52: “Overcoming Ven/Aza Resistance Through Imetelstat-Mediated Lipophagy in Acute Myeloid Leukemia”
Oral presentation on Saturday, December 7, 2024 at 10:15 a.m. PT by Claudia Bruedigam, Team Head, Leukaemia Metabolism Laboratory, QIMR Berghofer Medical Research Institute,
This abstract, submitted by Geron collaborators, shares pre-clinical data identifying imetelstat-mediated, ferroptosis-associated lipidomic alterations in AML cells that correlate with imetelstat treatment responses in vivo. These mechanistic insights may be leveraged to develop an optimized therapeutic strategy using imetelstat to target venetoclax/azacitidine resistant AML subclones.
About RYTELO™ (imetelstat)
RYTELO™ (imetelstat) is an FDA-approved oligonucleotide telomerase inhibitor for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks.
RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Thrombocytopenia
RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in
Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.
Neutropenia
RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in
Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.
Infusion-Related Reactions
RYTELO can cause infusion-related reactions. In the clinical trial, infusion-related reactions occurred in
Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended.
Embryo-Fetal Toxicity
RYTELO can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose.
ADVERSE REACTIONS
Serious adverse reactions occurred in
Most common adverse reactions (≥
Please see RYTELO (imetelstat) full Prescribing Information, including Medication Guide, available at https://pi.geron.com/products/US/pi/rytelo_pi.pdf.
About Geron
Geron is a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer. Our first-in-class telomerase inhibitor RYTELO™ (imetelstat) is approved in
Use of Forward-Looking Statements
Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such statements, include, without limitation, those regarding: (i) Geron’s plans to collaborate with trial investigators across the imetelstat pipeline and its belief in telomerase inhibition as an important and powerful approach to treating myeloid hematologic malignancies; (ii) results from an analysis of imetelstat-treated patients pooled from the IMerge Phase 2, Phase 3 and QTc studies that suggests that patients with lower-risk MDS who have symptomatic anemia and are transfusion dependent experience a clinical benefit with imetelstat regardless of their prior treatment; (iii) observation of sustained improvement in fatigue and maintenance of quality of life and anemia symptoms with imetelstat shown in post-hoc analyses that are meaningful and encouraging; (iv) the potential tolerability of imetelstat as a combination therapy; and (v) other statements that are not historical facts, constitute forward-looking statements. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (a) whether Geron is successful in commercializing RYTELO (imetelstat) for the treatment of certain patients with LR-MDS with transfusion dependent anemia; (b) whether Geron overcomes potential delays and other adverse impacts caused by enrollment, clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing and regulatory challenges in order to have the financial resources for and meet expected timelines and planned milestones; (c) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (d) whether any future safety or efficacy results of imetelstat treatment cause the benefit-risk profile of imetelstat to become unacceptable; (e) whether imetelstat actually demonstrates disease-modifying activity in patients and the ability to target the malignant stem and progenitor cells of the underlying disease; (f) that Geron may seek to raise substantial additional capital in order to continue the development and commercialization of imetelstat; (g) whether Geron meets its post-marketing requirements and commitments in the
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Source: Geron Corporation
FAQ
What are the key findings from Geron's (GERN) IMerge clinical trial for imetelstat?
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What were the main adverse events reported in Geron's (GERN) QTc substudy?
