Hydrocortisone

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 new analyses presented at the 66 th American Society of Hematology (ASH) Annual Meeting from the IMerge clinical trial in patients with lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia suggesting clinical activity of first-in-class telomerase inhibitor RYTELO™ (imetelstat) regardless of type or number of prior therapies, as well as favorable patient-reported outcomes (PROs). “ 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, 90% had prior treatment with an erythropoiesis-stimulating agent (ESA), 12% had prior treatment with lenalidomide, 16% had prior treatment with luspatercept and 10% had prior treatment with a hypomethylating agent (HMA). Across this pooled population, median imetelstat treatment duration was 33.6 weeks (range: 0.1-260.1 weeks). 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), 41% of patients (n=21) achieved ≥8-week RBC-TI, 25% of patients (n=13) achieved ≥24-week RBC-TI, 41% of patients (n=21) achieved hematologic improvement-erythroid (HI-E) per IWG 2018 criteria, 35% of patients (n=18) had hemoglobin rises ≥1.5 g/dL lasting ≥8 weeks and 75% of patients (n=38) had RBC transfusion reductions ≥4 U/8 weeks. In patients with prior luspatercept, lenalidomide or HMA (azacitidine or decitabine) treatment, 30% (7/23), 38% (5/13), and 21% (3/14) of patients achieved ≥8-week RBC-TI, and 22% (5/23) 15% (2/13), and 14% (2/14) achieved ≥24-week RBC-TI, respectively. Patients treated with imetelstat showed no treatment-related changes in absolute and change in QTcF nor clinically meaningful effects on cardiac repolarization compared with placebo. 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 U.S. Food and Drug Administration. 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 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 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 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 . 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) 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 U.S. for RYTELO for the treatment of certain 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 certain 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; (j) whether Geron stays in compliance with and satisfies its obligations under its debt and royalty financing agreements; and (k) 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 September 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.

Amglidia® has been approved by the European Medicines Agency (EMA) and is commercially available in EuropeStrong strategic fit with Eton’s existing pediatric endocrinology focusAmglidia has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA)Potential New Drug Application (NDA) submission in 2026 DEER PARK, Ill., Nov. 25, 2024 (GLOBE NEWSWIRE) -- Eton Pharmaceuticals, Inc (“Eton” or the “Company”) (Nasdaq: ETON), an innovative pharmaceutical company focused on developing and commercializing treatments for rare diseases, today announced that it has acquired the U.S. rights to Amglidia (glyburide oral suspension, known as glibenclamide in Europe) for the treatment of neonatal diabetes mellitus from AMMTeK. “This exciting transaction adds another attractive, patented product candidate to our growing pediatric endocrinology portfolio. In addition, the product aligns with Eton’s expertise and wealth of experience in bringing to market liquid and precision dose formulations for pediatric patients,” said Sean Brynjelsen, CEO of Eton Pharmaceuticals. “Currently, there are no FDA-approved oral treatments for neonatal diabetes mellitus. Amglidia has been used successfully to treat European patients for years, and families and pediatric endocrinologists have expressed to us the significant need for this treatment in the United States. We look forward to working with AMMTeK to bring the product to U.S. patients as quickly as possible,” concluded Brynjelsen. Amglidia is a proprietary, patented liquid product that was developed for the treatment of neonatal diabetes mellitus by AMMTeK, a French biotechnology company. The product was approved by the EMA in 2018. The product has already been granted Orphan Drug Designation by the U.S. FDA. Neonatal diabetes mellitus is a rare condition estimated to impact approximately 300 patients in the United States. Currently, there are no FDA-approved oral treatment options and as a result, U.S. patients frequently either rely on compounded products that are not FDA-approved or administer products off-label by making homemade suspensions. AMMTeK has conducted a post-approval study tracking five years of real-world safety and efficacy in European patients, which will be used to support Eton’s NDA submission. Eton plans to hold a meeting with the FDA in the first quarter of 2025 and anticipates submitting an NDA for the product in 2026. About Eton Pharmaceuticals Eton is an innovative pharmaceutical company focused on developing and commercializing treatments for rare diseases. The Company currently has five commercial rare disease products: ALKINDI SPRINKLE®, PKU GOLIKE®, Carglumic Acid, Betaine Anhydrous, and Nitisinone. The Company has three additional product candidates in late-stage development: ET-400, ET-600, and ZENEO® hydrocortisone autoinjector. For more information, please visit our website at www.etonpharma.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements associated with the expected ability of Eton to undertake certain activities and accomplish certain goals and objectives. These statements include but are not limited to statements regarding Eton’s business strategy, Eton’s plans to develop and commercialize its product candidates, the safety and efficacy of Eton’s product candidates, Eton’s plans and expected timing with respect to regulatory filings and approvals, and the size and growth potential of the markets for Eton’s product candidates. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Eton’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. These and other risks concerning Eton’s development programs and financial position are described in additional detail in Eton’s filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Eton undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Investor Relations:Lisa M. Wilson, In-Site Communications, Inc.T: 212-452-2793E: lwilson@insitecony.com