- IMpactMF is the first and only Phase 3 clinical trial to evaluate overall survival as the primary endpoint in R/R MF
- An interim analysis is expected in the first half of 2025, with a final analysis expected in the first half of 2026
Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, today announced achievement of fifty percent enrollment in the Phase 3 IMpactMF clinical trial investigating the Company’s first-in-class telomerase inhibitor, imetelstat, versus best available therapy (BAT) in patients with relapsed/refractory myelofibrosis (MF).
“Reaching fifty percent enrollment in IMpactMF is an important milestone towards the completion of this first-of-its-kind registration-enabling trial, and we are very grateful to all of the investigators, research staff and patients who are participating,” said Faye Feller, M.D., Executive Vice President, Geron’s Chief Medical Officer. “This is the first Phase 3 trial to evaluate overall survival as a primary endpoint in relapsed/refractory MF and is also the first Phase 3 trial investigating a telomerase inhibitor in this patient population. We believe that if IMpactMF confirms the clinical benefits of symptom response and overall survival observed in the Phase 2 IMbark study, that imetelstat could become a standard of care in relapsed/refractory myelofibrosis.”
“Today’s myelofibrosis treatments include JAK inhibitor and JAK inhibitor combination therapies which can improve symptoms and decrease spleen volume. However, once patients fail or no longer respond to JAK inhibitors, which occurs in 75% of patients within 5 years, these heavily pre-treated patients have a dismal median overall survival of only approximately 14 – 16 months,” said John Mascarenhas, M.D., Professor of Medicine at the Icahn School of Medicine at Mount Sinai, and principal investigator of IMpactMF. “There is therefore a very pressing need for treatments that can improve survival in relapsed/refractory MF. I believe that if IMpactMF reads out positively, hematologists would welcome a new mechanism into their MF armamentarium and would consider overall survival a gold standard clinical outcome.”
IMpactMF is an open label, randomized, controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 320 patients with Intermediate-2 or High-risk myelofibrosis (MF) who are relapsed after or refractory to prior treatment with a JAK inhibitor, also referred to as relapsed/refractory MF. Patients will be randomized to receive either imetelstat or best available therapy. The primary endpoint is overall survival (OS). Key secondary endpoints include symptom response, spleen response, progression free survival, complete remission, partial remission, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.
An interim analysis is expected when ~35% of the planned enrolled patients have died (alpha spend ~0.01), and a final analysis is expected when more than 50% of the planned enrolled patients have died. Based on projected planning assumptions for enrollment and death rates in the trial, interim analysis is expected in the first half of 2025 and final analysis is expected in the first half of 2026.
The Phase 3 IMpactMF clinical trial is based on results from IMbark Phase 2, in which the 9.4 mg/kg dose every three weeks demonstrated clinical benefits in symptom response rate, with an acceptable safety profile for this poor-risk JAKi relapsed/refractory MF patient population. Biomarker and bone marrow assessments suggested selective effects on the malignant clone. A median OS of 29.9 months in imetelstat 9.4 mg/kg arm was observed in IMbark Phase 2, compared to 14-16 months median OS for historical controls for these JAKi relapsed/refractory MF patients.
Imetelstat is a novel, first-in-class investigational telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk myelofibrosis (MF) whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment. Imetelstat is currently not approved by any regulatory authority.
Geron is a late-stage clinical biopharmaceutical company pursuing therapies with the potential to extend and enrich the lives of patients living with hematologic malignancies. Our first-in-class investigational telomerase inhibitor, imetelstat, harnesses Nobel Prize-winning science in a treatment that may alter the underlying drivers of disease. The New Drug Application (NDA) for imetelstat for the treatment of transfusion dependent anemia in patients with lower risk myelodysplastic syndromes (LR MDS) who have failed to respond or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs), based on the results from the Phase 3 IMerge clinical trial, is currently under review by the United States Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of June 16, 2024. In addition, an MAA is under review in the European Union for the same proposed indication. Furthermore, Geron currently has an ongoing pivotal Phase 3 clinical trial evaluating imetelstat in relapsed/refractory myelofibrosis (MF). 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: (i) the expected timing for the interim analysis and final analysis of the Phase 3 IMpactMF clinical trial; (ii) that IMpactMF is a registration-enabling trial and that, if approved, that imetelstat could become a standard of care in relapsed/refractory myelofibrosis; (iii) that there is a pressing need for treatments that can improve survival in relapsed/refractory MF and that, if IMpactMF reads out positively, hematologists would welcome a new mechanism into their MF armamentarium and would consider overall survival a gold standard clinical outcome; (iv) that imetelstat may alter the underlying drivers of disease in myeloid hematologic malignancies and has the potential to demonstrate disease-modifying activity in patients; 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 regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (b) whether any future safety or efficacy results cause the benefit-risk profile of imetelstat to become unacceptable; (c) whether imetelstat actually demonstrates that it alters the underlying drivers of disease and has disease-modifying activity in patients; (d) whether the timelines for the interim and final analysis of the Phase 3 IMpactMF trial will occur when expected and whether the results from the trial will support regulatory approval; and (e) whether the FDA and EMA will approve imetelstat for the treatment of transfusion-dependent anemia in patients with lower risk MDS. 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, 2023 and future 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.