Geron Announces New IMerge Analyses Presented at ASH Suggesting Clinical Activity of RYTELO™ (imetelstat) in Patients with Lower-Risk MDS Regardless of Type or Number of Prior Therapies
Geron (GERN) presented new analyses from the IMerge clinical trial at the 66th ASH Annual Meeting, demonstrating RYTELO™ (imetelstat)'s clinical activity in lower-risk myelodysplastic syndromes (LR-MDS) patients. The data suggests effectiveness regardless of prior therapies, including in patients who previously received luspatercept or lenalidomide.
Key findings from pooled data of 226 imetelstat-treated patients showed consistent clinical activity with the IMerge Phase 3 pivotal trial. The QTc substudy demonstrated an absence of proarrhythmic risk and confirmed efficacy in patients with prior treatments. Patient-reported outcomes showed sustained improvement in fatigue and maintenance of quality of life compared to placebo.
Geron (GERN) ha presentato nuove analisi dal trial clinico IMerge durante il 66° Congresso Annuale dell'ASH, dimostrando l'attività clinica di RYTELO™ (imetelstat) nei pazienti con sindromi mielodisplastiche a basso rischio (LR-MDS). I dati suggeriscono un'efficacia indipendentemente dalle terapie precedenti, inclusi i pazienti che hanno ricevuto in precedenza luspatercept o lenalidomide.
I principali risultati dai dati aggregati di 226 pazienti trattati con imetelstat hanno mostrato un'attività clinica coerente con il trial pivotale di fase 3 IMerge. Lo studio secondario QTc ha dimostrato l'assenza di rischio proaritmico e confermato l'efficacia nei pazienti con trattamenti precedenti. Gli esiti riportati dai pazienti hanno mostrato un miglioramento sostenuto nella fatica e il mantenimento della qualità della vita rispetto al placebo.
Geron (GERN) presentó nuevos análisis del ensayo clínico IMerge en la 66ª Reunión Anual de la ASH, demostrando la actividad clínica de RYTELO™ (imetelstat) en pacientes con síndromes mielodisplásicos de bajo riesgo (LR-MDS). Los datos sugieren eficacia independientemente de las terapias previas, incluidos los pacientes que recibieron previamente luspatercept o lenalidomida.
Los hallazgos clave de los datos agrupados de 226 pacientes tratados con imetelstat mostraron actividad clínica consistente con el ensayo pivotal Fase 3 IMerge. El estudio secundario QTc demostró la ausencia de riesgo proarrítmico y confirmó la eficacia en pacientes con tratamientos previos. Los resultados autoinformados por los pacientes mostraron una mejora sostenida en la fatiga y el mantenimiento de la calidad de vida en comparación con el placebo.
Geron (GERN)은 제66회 ASH 연례 회의에서 IMerge 임상 시험의 새로운 분석 결과를 발표하였으며, 이는 RYTELO™ (imetelstat)의 저위험 골수형성이상 증후군 (LR-MDS) 환자에서의 임상 활동성을 보여줍니다. 데이터는 이전 치료에 관계없이 효과를 제시하며, luspatercept 또는 lenalidomide를 이전에 받은 환자들에서도 마찬가지입니다.
임etelstat로 치료받은 226명의 환자로부터의 집계된 데이터의 주요 발견은 IMerge 3상 주요 시험과 일관된 임상 활동성을 나타냈습니다. QTc 하위 연구는 부정맥 위험이 없음을 입증하였고, 이전 치료를 받은 환자에서의 효능을 확인하였습니다. 환자가 보고한 결과는 피로의 지속적인 개선과 위약에 비해 삶의 질 유지의 향상을 보여주었습니다.
Geron (GERN) a présenté de nouvelles analyses de l'essai clinique IMerge lors de la 66ème réunion annuelle de l'ASH, démontrant l'activité clinique de RYTELO™ (imetelstat) chez les patients présentant des syndromes myélodysplasiques à faible risque (LR-MDS). Les données suggèrent une efficacité indépendamment des traitements antérieurs, y compris chez les patients ayant précédemment reçu du luspatercept ou de la lenalidomide.
Les résultats clés des données regroupées de 226 patients traités par imetelstat ont montré une activité clinique constante avec l'essai pivot de phase 3 IMerge. L'étude secondaire QTc a montré l'absence de risque proarythmique et confirmé l'efficacité chez les patients ayant bénéficié de traitements antérieurs. Les résultats rapportés par les patients ont montré une amélioration soutenue de la fatigue et le maintien de la qualité de vie par rapport au placebo.
Geron (GERN) präsentierte neue Analysen aus der klinischen IMerge-Studie auf dem 66. Jahresmeeting der ASH und demonstrierte die klinische Aktivität von RYTELO™ (imetelstat) bei Patienten mit niedrigem Risiko für myelodysplastische Syndrome (LR-MDS). Die Daten legen nahe, dass die Wirksamkeit unabhängig von vorherigen Therapien besteht, auch bei Patienten, die zuvor Luspatercept oder Lenalidomid erhalten hatten.
Die wichtigsten Ergebnisse aus den zusammengefassten Daten von 226 mit Imetelstat behandelten Patienten zeigten eine konsistente klinische Aktivität mit der entscheidenden Phase-3-Studie IMerge. Die QTc-Substudie bestätigte das Fehlen eines proarrhythmischen Risikos und bestätigte die Wirksamkeit bei Patienten mit vorherigen Behandlungen. Die von den Patienten berichteten Ergebnisse zeigten eine anhaltende Verbesserung der Müdigkeit und die Aufrechterhaltung der Lebensqualität im Vergleich zu Placebo.
- Clinical efficacy demonstrated across different patient groups, including those who failed prior treatments
- Positive patient-reported outcomes showing sustained improvement in fatigue
- Favorable safety profile with absence of proarrhythmic risk
- 41% of patients achieved ≥8-week RBC transfusion independence in the QTc substudy
- 75% of patients showed RBC transfusion reductions ≥4 U/8 weeks
- Lower efficacy in patients with prior HMA treatment, showing only modest clinical activity
- analysis due to small patient groups in some categories
Insights
The new IMerge analyses significantly strengthen RYTELO™'s (imetelstat) clinical profile in lower-risk MDS patients. The pooled data from 226 patients demonstrates robust efficacy across different prior treatment scenarios, with 90% having prior ESA treatment. Key efficacy measures showed positive outcomes regardless of previous therapies, particularly in ESA-ineligible patients and those previously treated with luspatercept or lenalidomide.
The QTc substudy data is particularly compelling, showing 41% of patients achieving ≥8-week RBC transfusion independence and 25% reaching ≥24-week independence. The absence of cardiac repolarization concerns addresses an important safety consideration. Patient-reported outcomes showing sustained improvement in fatigue and quality of life metrics provide important real-world validation of the treatment's clinical benefits.
These comprehensive analyses significantly enhance RYTELO's commercial positioning as a second-line treatment option. The data showing efficacy regardless of prior treatments expands the potential patient pool and could drive broader adoption among physicians. The positive patient-reported outcomes, particularly regarding fatigue improvement and quality of life maintenance, provide compelling evidence for payers and should support reimbursement discussions.
The robust safety profile and versatility across different patient subgroups could help RYTELO capture significant market share in the lower-risk MDS space. This positions Geron well in a market segment with treatment options, potentially leading to stronger revenue growth as market penetration increases.
- Analyses pooling data from IMerge Phase 2, Phase 3 and the QTc substudy suggest patients who were ESA ineligible or who had prior treatment with luspatercept or lenalidomide experienced clinical benefit from imetelstat similar to prior results from the IMerge pivotal trial
- Data from the QTc substudy reinforce imetelstat as a second-line treatment option for LR-MDS patients with transfusion-dependent anemia regardless of prior therapies, including luspatercept and lenalidomide
- A patient-reported outcome analysis from IMerge Phase 3 showed sustained improvement in fatigue and maintenance of quality of life and anemia symptoms with imetelstat compared with placebo
“These latest IMerge analyses presented at ASH contribute to a growing body of clinical evidence that support RYTELO as a second-line option in red blood cell transfusion-dependent lower-risk MDS, regardless of prior treatments,” said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. “Additionally, the sustained improvement in fatigue observed in the IMerge Phase 3 patient-reported outcomes population is meaningful for this progressive disease that is characterized by fatigue.”
“Patients with red blood cell transfusion-dependent lower-risk MDS often cycle through limited available therapies. The IMerge data presented at ASH suggesting clinical activity of imetelstat regardless of prior therapies, offers physicians important clinical evidence while assessing sequencing of treatments,” said Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, an investigator of the IMerge clinical trial, who presented IMerge results at ASH. “Further, anemia and fatigue remain two of the most burdensome symptoms of lower-risk MDS, and patient-reported outcomes such as improvement in fatigue and maintenance of quality of life and anemia symptoms may inform treatment choices as we aim to improve outcomes for our patients.”
“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”
This oral presentation reported findings from analyses investigating the effects of prior therapies on the clinical activity of imetelstat using pooled data from IMerge Phase 2, Phase 3, and the QTc substudy. Of the 226 total imetelstat-treated LR-MDS patients included in this analysis,
Imetelstat clinical activity was observed in the pooled patient population consistent with that of the IMerge Phase 3 pivotal trial with regards to safety and critical efficacy measures that include ≥8-week red blood cell transfusion independence (RBC-TI), ≥24-week RBC-TI, RBC transfusion reduction ≥4 U/8 weeks and hemoglobin rise ≥1.5 g/dL/8 weeks.
The results suggest that patients who were ESA ineligible, patients who had prior treatment with luspatercept or lenalidomide, or patients who had prior treatment with ESAs followed by luspatercept or lenalidomide experienced clinical benefit from imetelstat treatment similar to that demonstrated in the IMerge Phase 3 pivotal trial. Patients who had prior treatment with HMAs, or with ESAs followed by HMAs, showed modest clinical activity with imetelstat. Overall, while these analyses were limited by the small number of patients in each group, imetelstat showed clinical activity regardless of prior ESA response status and regardless of the number of prior lines of therapy.
“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”
This poster presentation reports initial results from the ventricular repolarization (QTc) substudy of IMerge conducted per FDA guidance. This substudy differed from the IMerge Phase 3 trial in its crossover design, the inclusion of patients with del(5q) MDS, and by allowing prior lenalidomide and HMA therapy besides ESAs. The QTc substudy population comprised 53 treated patients (n=35 imetelstat, n=18 placebo). As of the data cutoff on May 10, 2024, 16 of 18 placebo recipients crossed over to receive imetelstat. Median treatment duration on imetelstat, including crossover (n=51) was 29.3 weeks; median duration in the imetelstat group (n=35) was 37.0 weeks and median duration in the crossover group (n=16) was 27.9 weeks.
In the total imetelstat population (n=51),
In patients with prior luspatercept, lenalidomide or HMA (azacitidine or decitabine) treatment,
The poster concludes that in this QTc substudy, imetelstat was associated with an absence of proarrhythmic risk, durable RBC-TI, transfusion reduction, clinically meaningful increases in hemoglobin, and a safety profile comparable to the overall population of the pivotal Phase 3 IMerge trial. RBC-TI was attained in imetelstat-treated patients who received prior therapies with HMA, luspatercept and lenalidomide, supporting the use of imetelstat in patients with relapsed or refractory LR-MDS regardless of prior therapies.
“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”
This poster reports on the exploratory PRO analysis from IMerge Phase 3, with a data cutoff of October 2022. PROs were assessed with validated using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Functional Assessment of Cancer Therapy-Anemia (FACT-An), and Quality of Life in Myelodysplasia Scale (QUALMS) questionnaires. Sustained meaningful improvement in fatigue was defined as a ≥3-point increase in FACIT-Fatigue score for ≥2 consecutive assessments. The PRO population (n=175) included all patients in the intent-to-treat population who had FACIT-Fatigue data at baseline and consisted of 118 imetelstat-treated patients and 57 patients who received placebo.
In the subgroup analysis, more patients treated with imetelstat than placebo reported sustained improvement in fatigue regardless of ring sideroblast (RS) status, prior transfusion burden and baseline serum EPO levels. Additionally, improvement in fatigue was seen in more patients who responded to imetelstat versus those who did not across measures of response including RBC-TI, hemoglobin rise and transfusion reduction. The QUALMS and FACT-An analyses suggested that imetelstat maintained QOL and anemia symptoms, while placebo recipients experienced worsening QOL and anemia symptoms.
The poster concludes that data from the pivotal IMerge phase 3 trial showed that improvement in fatigue with imetelstat was associated with reduced transfusion burden and a rise in hemoglobin and that imetelstat appears to offer the advantage of sustained RBC-TI benefit while maintaining QOL in patients with LR-MDS with TD anemia.
The ASH presentations are available on Geron’s website in the investor section under publications.
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) that the IMerge analyses presented at ASH contribute to a growing body of clinical evidence that support RYTELO as a second-line option in red blood cell transfusion-dependent lower-risk MDS, regardless of prior treatments; (ii) that sustained improvement in fatigue observed in the IMerge Phase 3 patient-reported outcomes population is meaningful for this progressive disease that is characterized by fatigue; (iii) that the IMerge data presented at ASH suggests clinical activity of imetelstat regardless of prior therapies, offering physicians important clinical evidence while assessing sequencing of treatments; (iv) that patient-reported outcomes such as improvement in fatigue and maintenance of quality of life and anemia symptoms may inform treatment choices for patients with lower-risk MDS; 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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Aron Feingold
Vice President, Investor Relations and Corporate Communications
Kristen Kelleher
Associate Director, Investor Relations and Corporate Communications
investor@geron.com
media@geron.com
Source: Geron Corporation
FAQ
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