Imetelstat

FibroGen has reached agreement with the FDA on important design elements for a pivotal Phase 3 clinical trial for roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndromes (LR-MDS) and high red blood cell (RBC) transfusion burden Company intends to file the Phase 3 protocol in the fourth quarter of 2025 Aug. 07, 2025 -- FibroGen, Inc. (NASDAQ: FGEN) today announced positive feedback from its Type C meeting with the FDA, supporting the advancement of roxadustat for the treatment of anemia in patients with LR-MDS and high RBC transfusion burden, based on a post-hoc subgroup analysis from the MATTERHORN Phase 3 trial. “We are very pleased with the feedback we received from the FDA regarding roxadustat in patients with LR-MDS and anemia with high transfusion burden. This indication, despite recent approvals, still represents a patient population with significant unmet need,” said Thane Wettig, Chief Executive Officer of FibroGen. “We believe roxadustat’s differentiated mechanism of action, favorable tolerability profile, and oral route of administration can potentially be an important addition to the treatment options for patients with high transfusion burden. We are starting preparations for the Phase 3 trial, while evaluating internal development and potential partnership opportunities for this late-stage program. We plan to submit the Phase 3 trial protocol to the FDA in the fourth quarter of this year.” “Anemia is a major cause of morbidity and complications in patients with LR-MDS, especially those with high transfusion burden, and is often associated with poor quality of life and shortened survival. While we have recent approvals of injectable drugs for this indication, there is a significant unmet need for novel, effective oral agents for this patient population,” added Amer Zeidan, M.B.B.S, M.H.S., Professor of Medicine at Yale School of Medicine and Chief of the Division of Hematologic Malignancies at Yale Cancer Center, and the global principal investigator of the planned Phase 3 study. “Roxadustat has already shown promising efficacy in this group of patients in the post-hoc analysis of the MATTERHORN study, and I am glad we have agreed on a pathway with the regulators to explore the full potential of roxadustat in the upcoming Phase 3 trial. I am excited by the prospect of roxadustat potentially becoming a novel, safe, convenient, and effective therapy for LR-MDS patients with high transfusion burden. FibroGen requested the Type C meeting based on the findings of a post-hoc analysis of data from the Phase 3 MATTERHORN trial of roxadustat in anemia-associated with LR-MDS. In patients with high RBC transfusion burden at baseline (≥4 units over 8 weeks1), a pronounced treatment effect was observed: 36% (8/22) of patients achieved transfusion independence (TI) for ≥ 56 days on roxadustat vs 7% (1/15) of patients on placebo within 28 weeks (nominal p-value of 0.041). The planned Phase 3 trial will assess the safety and efficacy of roxadustat in a randomized, double-blind, placebo-controlled design in approximately 200 patients with LR-MDS. Alignment was reached with the FDA on the patient population (patients requiring ≥ 4 pRBC units in two consecutive 8-week periods prior to randomization, who are refractory to, intolerant to, or ineligible for prior erythropoiesis-stimulating agents (ESA) therapy), dose regimen, as well as management of potential thrombotic risk through eligibility and dose modification and discontinuation criteria. As the primary endpoint for the study, the Company is considering either 8-week or 16-week RBC TI. Myelodysplastic syndromes (MDS) are a group of disorders characterized by dysfunctional progenitor blood cells and stem cells, resulting in chronic anemia in most patients. Annual incidence rates of MDS are estimated to be 4.9/100,000 adults in the U.S, thereof 77% are considered lower-risk MDS. Approximately 80% of patients with MDS have anemia at the time of diagnosis, and around 60% of patients with MDS will experience severe anemia (hemoglobin <8 g/dL) at some point during the course of their disease. Anemia in patients with MDS is associated with increased risk of cardiovascular complications and the need for blood transfusion. Approximately 50% of patients with MDS require regular red blood cell transfusions. Transfusion dependent MDS patients suffer higher rates of cardiac events, infections, and iron overload with the related complications. In addition, anemia frequently leads to significant fatigue, cognitive dysfunction, and decreased quality of life. Today, patients are routinely treated with erythropoiesis-stimulating agents (ESAs), luspatercept, imetelstat, or lenalidomide in lower-risk MDS with isolated del(5q), and hypomethylating agents (HMAs) in higher-risk disease. Only 35-40% of patients respond to current treatments and the durability of response is short. Moreover, these treatments are challenging to dose-calibrate and can only be administered via subcutaneous injection or through IV infusion. There remains a high unmet need for the treatment of anemia associated with MDS, and new strategies that provide durable response and the convenience of oral administration are highly desired in managing patients with MDS. Roxadustat, an oral medication, is the first in a new class of medicines comprising HIF-PH inhibitors that promote erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin, improved iron absorption and mobilization, and downregulation of hepcidin. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA) and a Supplemental New Drug Application (sNDA) has been accepted by the China Health Authority. Roxadustat is approved in China, Europe, Japan, and numerous other countries for the treatment of anemia of CKD in adult patients on dialysis (DD) and not on dialysis (NDD). FibroGen has the sole rights to roxadustat in the United States, Canada, Mexico, and in all markets not held by AstraZeneca or licensed to Astellas. Astellas and FibroGen are collaborating on the commercialization of roxadustat for the treatment of anemia in territories including Japan, Europe, Turkey, Russia, and the Commonwealth of Independent States, the Middle East, and South Africa. FibroGen, Inc. is a biopharmaceutical company focused on accelerating the development of novel therapies at the frontiers of cancer biology. Roxadustat (爱瑞卓®, EVRENZO™) is currently approved in China, Europe, Japan, and numerous other countries for the treatment of anemia in chronic kidney disease (CKD) patients on dialysis and not on dialysis. Roxadustat is in clinical development for chemotherapy-induced anemia (CIA) and a Supplemental New Drug Application (sNDA) has been accepted for review by the China Health Authority. FG-3246 (also known as FOR46), a first-in-class antibody-drug conjugate (ADC) targeting CD46 is in development for the treatment of metastatic castration-resistant prostate cancer. This program also includes the development of an associated CD46-targeted PET biomarker. In addition, FibroGen has expanded its research and development portfolio to include two immuno-oncology product candidates for the treatment of solid tumors. The content above comes from the network. if any infringement, please contact us to modify.

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 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). “Transfusion independence is an important goal for LR-MDS patients, but one that historically has not been achievable for many,” said Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center. “While imetelstat is already playing a vital role in LR-MDS, these new analyses being presented at ASCO and EHA reinforce its potential to give a broad range of patients more time without transfusions and should also give clinicians confidence to add it to their toolkit as a second-line option for eligible patients.” Presentations at ASCO and EHA include: New pooled, post-hoc analyses expand on the pivotal IMerge results across challenging LR-MDS subpopulations 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. Patients who had prior treatment with a hypomethylating agent (HMA) showed modest clinical activity with RYTELO. Patient-centric outcome measures offering deeper insight on RYTELO impact in new post-hoc analyses from Phase 3 IMerge trial 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. New updates on ongoing trials in MF Recently updated preliminary data from the dose escalation portion of the Phase 1/1b IMproveMF trial showing the combination of imetelstat and ruxolitinib was generally well-tolerated, with no dose-limiting toxicities observed as of the data cutoff date, and encouraging early dose-dependent efficacy data suggesting the potential of the combination for patients with intermediate-1 (INT-1), intermediate-2 (INT-2) or high-risk (HR) MF. Trial-in-progress (TiP) update on the Phase 3 IMpactMF trial investigating imetelstat in relapsed/refractory MF, reporting that the trial has met approximately 80% of its enrollment target as of February 2025. “At ASCO and EHA, we’re excited to present new analyses on how RYTELO can deliver meaningful benefit across a range of LR-MDS patients who otherwise may have had limited options, whether due to their ring sideroblast status, baseline EPO level, or their treatment history,” said Faye Feller, M.D., Executive Vice President and Chief Medical Officer of Geron. “We believe the depth and breadth of our data reinforce the potential of RYTELO to address critical unmet needs in LR-MDS and, combined with the advances we are making with our myelofibrosis program, underscore our confidence in telomerase inhibition as a potentially transformative clinical strategy and our commitment to exploring its full potential.” See below for a full schedule of presentations at ASCO and EHA. ASCO 2025 Presentations Presentation Title Author Abstract Number Presentation Details 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) John O. Mascarenhas, M.D. #6515 Rapid Oral, Fri. May 30, 1:00-2:30 PM CDT 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) Rami S. Komrokji, M.D. #6569 Poster, Sun. June 1, 9:00 AM-12:00 PM CDT 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) John O. Mascarenhas, M.D. #TPS6588 Poster, Sun. June 1, 9:00 AM-12:00 PM CDT EHA 2025 Presentations Presentation Title Author Abstract Number Presentation Details Increased Duration of Time Without Transfusion Reliance (TWiTR) For Patients with LR-MDS Treated with Imetelstat Versus Placebo in the IMerge Trial Mikkael A. Sekeres, M.D. #PF646 Poster, Fri. June 13, 18:30-19:30 CEST IMproveMF Update: Phase 1/1B Trial of Imetelstat + Ruxolitinib in Patients with INT-1, INT-2, or High-Risk MF John O. Mascarenhas, M.D. #PF830 Poster, Fri. June 13, 18:30-19:30 CEST IMpactMF: Randomized, Open-Label, Phase 3 Trial of Imetelstat vs Best Available Therapy in Patients with INT-2 or High-Risk MF Relapsed/Refractory to JAK Inhibitors John O. Mascarenhas, M.D. #PF841 Poster, Fri. June 13, 18:30-19:30 CEST Health-related Quality of Life Outcomes in Patients with Lower-Risk Myelodysplastic Syndromes Treated with Imetelstat in the IMerge Trial María Díez-Campelo, M.D., Ph.D. #PS1639 Poster, Sat. June 14, 18:30-19:30 CEST Outcomes of Imetelstat Therapy in RS-Negative LR-MDS from the Pooled IMerge Study Populations Valeria Santini, M.D. #PS1622 Poster, Sat. June 14, 18:30-19:30 CEST Outcomes with Imetelstat by Serum Erythropoietin Levels in Patients with LR-MDS Who Were Treatment Naïve or Who Had Prior Treatment with Erythropoiesis-Stimulating Agents Rami S. Komrokji, M.D. #PS1640 Poster, Sat. June 14, 18:30-19:30 CEST Characterization and Management of Transient Cytopenias Associated with Imetelstat in LR-MDS from the IMerge Trial Amer M. Zeidan, M.D. #PB2760 Publication-only Please see the full presentations for important qualifications and limitations on these post-hoc analyses. About RYTELO® (imetelstat) RYTELO is an oligonucleotide telomerase inhibitor approved in the U.S. 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. In addition, RYTELO is approved in the European Union as a monotherapy for the treatment of adult patients with transfusion-dependent anemia due to very low, low or intermediate risk myelodysplastic syndromes without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy. 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 U.S. Food and Drug Administration and the European Commission. 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 and the European Union 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 LinkedIn. US IMPORTANT SAFETY INFORMATION ABOUT RYTELO® 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 65% of patients with MDS treated with RYTELO. 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 72% of patients with MDS treated with RYTELO. 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 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion. Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for at least 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 Based on animal findings, 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 32% of patients who received RYTELO. Serious adverse reactions in >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. The Summary of Product Characteristics (SmPC) for RYTELO in the EU is available at https://pi.geron.com/products/rytelo/eu/rytelo_smpc_eu.pdf 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 new analyses presented at ASCO and EHA reinforce the potential benefits of RYTELO for a range of patients with LR-MDS with transfusion-dependent anemia, including its potential to give a broad range of patients more time without transfusions and should support clinician’s confidence in RYTELO as a second-line option for eligible patients; (ii) beliefs regarding imetelstat’s vital role in LR-MDS, (iii) how RYTELO can deliver meaningful benefit across a range of LR-MDS patients who otherwise may have had limited options, whether due to ring sideroblast status, baseline EPO levels, or their treatment history; (iv) Geron’s beliefs that the depth and breadth of its data reinforce the potential of RYTELO to address critical unmet needs in LR-MDS and regarding telomerase inhibition as a potentially transformative clinical strategy; 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 and achieves market acceptance across the breadth of the eligible patient segments in RYTELO’s approved indication; (b) whether the FDA and European Commission will approve imetelstat for other indications on the timelines expected, or at all; (c) Geron’s plans to commercialize RYTELO in the European Union, or EU and risks related to operating outside of the U.S.; (d) whether Geron overcomes potential delays and other adverse impacts that may be 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; (e) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (f) whether any future safety or efficacy results of RYTELO treatment cause its benefit-risk profile to become unacceptable; (g) whether imetelstat actually demonstrates disease-modifying activity in patients and the ability to target the malignant stem and progenitor cells of the underlying disease; (h) whether Geron meets its post-marketing requirements and commitments for RYTELO; (i) whether there are failures or delays in manufacturing or supplying sufficient quantities of RYTELO (imetelstat) or other clinical trial materials that impact commercialization of RYTELO or the continuation of its ongoing clinical trials, including the IMpactMF trial; (j) 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 (k) whether Geron stays in compliance with and satisfies its obligations under its debt and synthetic royalty financing agreements. 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 March 31, 2025, 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.