Geron Stops Phase 3 Imetelstat Trial in Myelofibrosis

The phase 3 IMpactMF trial of imetelstat (Rytelo) in relapsed or refractory myelofibrosis is being stopped by Geron after independent monitors said the study was unlikely to meet its overall survival goal, the company announced Oct. 28 in an SEC filing. The monitoring committee did not identify new safety signals that would change imetelstat's known profile.

In myelofibrosis, scar tissue accumulates in the marrow and makes it harder for the body to produce blood cells. JAK inhibitors can reduce spleen size and ease symptoms, but they are not a cure and patients often lose response over time. Imetelstat is a telomerase inhibitor, a different approach from JAK inhibitors, which are often used to control myelofibrosis symptoms and an enlarged spleen.

The randomized, open-label study enrolled 327 people with intermediate-2 or high-risk myelofibrosis and assigned them in a 2:1 ratio to intravenous imetelstat 9.4 mg/kg every three weeks or best available therapy. Eligible participants had primary myelofibrosis, post-essential thrombocythemia myelofibrosis, or post-polycythemia vera myelofibrosis, with measurable splenomegaly and active symptoms; they were also ineligible for allogeneic stem cell transplantation. Overall survival was the primary endpoint. Secondary endpoints included symptom response and progression-free survival, along with spleen response, complete remission, changes in bone marrow fibrosis, and safety.

Joseph Eid, Geron's chief medical officer, said ending the trial "at this time is the right course of action". Rytelo's existing approvals are not affected by the myelofibrosis decision. The FDA approved imetelstat in June 2024 for a lower-risk myelodysplastic syndrome population that depends on blood transfusions, and the drug is also approved in the European Union. Geron said it will continue to expand U.S. use of Rytelo and access for eligible patients outside the U.S..

No efficacy data from IMpactMF have been released. OncLive reported that the announcement did not state whether the monitors' recommendation came after a scheduled interim analysis. The company said it will complete a detailed analysis of the data and share findings later. Geron also plans to look for insights for future research while continuing its low-risk MDS commercial business.

Earlier phase 2 results suggested a survival benefit in this population, but those studies were smaller and often had no standard-treatment comparator; the IMpactMF outcome shows that such early signals may not hold up in a larger randomized trial. Medical Daily reported that the announcement is based on the monitoring committee's advice, has not been peer reviewed, and outside experts have not yet seen the underlying data.

For trial participants, Geron has not publicly detailed transition plans, though patients should expect guidance from their study site. Medical Daily also said participants should talk to their hematologist-oncologist before changing or stopping treatment.