Press release
Geron Announces New Data to be Presented at Upcoming ASH Annual Meeting Highlighting the Potential of RYTELO™ (imetelstat) in Myeloid Hematologic Malignancies
New analyses from the IMerge clinical trial suggest that imetelstat demonstrates clinical activity in patients with lower-risk MDS with transfusion-dependent
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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 FOSTER CITY, Calif. --(BUSINESS WIRE)-- Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, today announced the publication of abstracts containing new data highlighting the potential of RYTELO™ (imetelstat), a first-in-class telomerase inhibitor, in myeloid hematologic malignancies. Six abstracts have been accepted for presentation at the 66th American Society of Hematology (ASH) Annual Meeting taking place from December 7-10, 2024 , in San Diego, California and virtually. “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 , Leipzig, Germany 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) 40% 28% 64% 33% 43% Luspatercept (n=35) 29% 20% 69% 29% 26% Lenalidomide (n=26) 23% 12% 54% 19% 31% HMA (n=22) 14% 9% 50% 14% 18% *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. Additionally, in imetelstat-treated patients ineligible for ESA therapy (n=22) treated in the front-line, 36% and 14% achieved ≥8-week and ≥24-week RBC-TI, respectively, 41% met HI-E, 64% had a transfusion reduction of ≥4 U/8 weeks, and 2% had a Hb rise of ≥1.5 g/dL for ≥8 weeks. 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 (95% CI) duration of RBC-TI among ≥8-week RBC-TI responders was 52.6 weeks (40.9-non estimable). Subgroup analyses showed ≥8-week RBC-TI rates of 30% (7/23) and 50% (14/28) in patients with and without prior luspatercept, 38% (5/13) and 42% (16/38) in patients with and without prior lenalidomide, and 21% (3/14) and 49% (18/37) in patients with and without prior HMA use, respectively. No new safety signals emerged, and in the total imetelstat-treated population, Grade 3/4 neutropenia and thrombocytopenia by laboratory evaluation occurred in 65% (33/51) and 49% (25/51) of patients, respectively, of which most cases resolved to Grade ≤2 within four weeks; incidence was similar to the overall Phase 3 imetelstat-treated population. In this QTc substudy, efficacy and safety of imetelstat were comparable to that shown in the overall population of the IMerge Phase 3 trial, and notably, responses to imetelstat were seen in patients receiving prior treatments including luspatercept, lenalidomide, and HMAs. 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 55% and 43% of imetelstat-treated patients; differences (95% CI) versus placebo appeared to favor imetelstat (9% [−12, 29] for RS+ and 13% [−15, 36] for RS−). Similarly, in patients with prior transfusion burdens of 4-6 U/8 weeks or >6 U/8 weeks, respectively, sustained improvement in fatigue was achieved by 44% and 57% of imetelstat-treated patients; differences (95% CI) versus placebo appeared to favor imetelstat (8% [−15, 29] for 4-6 U/8 weeks and 11% [−13, 34] for >6 U/8 weeks). Similar to the RBC-TI response and improvement in fatigue association, for imetelstat-treated patients with versus in those without a ≥1.5-g/dL increase in hemoglobin lasting ≥8 weeks, improvements in fatigue were seen in 70% (28/40) versus 40% of patients, respectively (31/78; nominal P-value=.003); in those with versus in those without transfusion reduction of ≥4 U/8 weeks, improvements were seen in 69% (49/71) versus 21% of patients (10/47; nominal P-value 2% of patients included sepsis (4.2%) and fracture (3.4%), cardiac failure (2.5%), and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of patients who received RYTELO, including sepsis (0.8%). Most common adverse reactions (≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache. 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 the United States for the treatment of certain adult patients with lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia. We are also conducting a pivotal Phase 3 clinical trial of imetelstat in JAK-inhibitor relapsed/refractory myelofibrosis (R/R MF), as well as studies in other hematologic malignancies. Inhibiting telomerase activity, which is increased in malignant stem and progenitor cells in the bone marrow, aims to potentially reduce proliferation and induce death of malignant cells. To learn more, visit www.geron.com or follow us on LinkedIn . 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 U.S. for RYTELO for the treatment of patients with LR-MDS with transfusion dependent anemia; (h) whether there are failures or delays in manufacturing or supplying sufficient quantities of imetelstat or other clinical trial materials that impact commercialization of RYTELO for the treatment of patients with LR-MDS with transfusion dependent anemia or the continuation of the IMpactMF trial; (i) that the projected timing for the interim and final analyses of the IMpactMF trial may vary depending on actual enrollment and death rates in the trial; and (j) whether the EMA will approve RYTELO for the treatment of patients with LR-MDS with transfusion dependent anemia and whether the FDA and EMA will approve imetelstat for other indications on the timelines expected, or at all. Additional information on the above risks and uncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron’s filings and periodic reports filed with the Securities and Exchange Commission under the heading “Risk Factors” and elsewhere in such filings and reports, including Geron’s quarterly report on Form 10-Q for the quarter ended June 30, 2024 , and subsequent filings and reports by Geron . Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events, or circumstances. View source version on businesswire.com : https://www.businesswire.com/news/home/20241105848872/en/ Aron Feingold Vice President, Investor Relations and Corporate Communications Kristen Kelleher Associate Director, Investor Relations and Corporate Communications [email protected] [email protected] Source: Geron Corporation