Study meets primary and key secondary endpoints, showing clinically meaningful and statistically significant improvements.
Imetelstat (Geron Corporation), a first-in-class telomerase inhibitor, demonstrated positive results in individuals with lower risk in myelodysplastic syndromes (MDS) who are relapsed, refractory, or ineligible for erythropoiesis stimulating agents (ESA), according to findings from IMerge (NCT02598661) phase 3 clinical trials.
“The results from the IMerge phase 3 study were resoundingly positive, presenting compelling durability of transfusion independence, delivering on the promise of imetelstat and telomerase inhibition for these patients,” John Scarlett, MD, CEO and chairman of Geron said in a statement.
“This milestone is the first of many upcoming catalysts for Geron, with planned [United States] and [European Union] regulatory submissions in 2023, as well as preparations for a potential [United States] commercial launch. In addition, in 2024, we expect an interim analysis of the IMpactMF Phase 3 trial of imetelstat in relapsed/refractory myelofibrosis,” Scarlett said.
The trial met its primary efficacy endpoint of 8-week transfusion independence (TI), as well as the secondary endpoint of 24-week TI, demonstrating highly clinically meaningful and statistically significant benefit of imetelstat compared with the placebo with no new safety signals. The safety results were consistent with prior imetelstat clinical trials.
The IMerge phase 3 trial was a double-blinded, randomized, 2:1 clinical trial that evaluated the drug in individuals with international prognostic scoring system (IPSS) Low or Intermediate-1 risk transfusion dependent MDS who were relapsed after, refractory to, or ineligible for ESA treatment. Individuals also did not receive prior treatment with either a hypomethylating agent or lenalidomide and were non-del(5q).
The data cut-off occurred in October 2022, making the median time on study and median time on treatment for individuals on imetelstat approximately 20 and 8 months, respectively. For the placebo, the median times were 18 and 7 months, respectively.
Investigators reported that for the 8-week TI, approximately 39.8% of individuals on imetelstat and 15% on the placebo reached TI. For 24-week TI, 28% and 3.3% reached TI, respectively.
Highly statistically significant durable TI for 8 weeks was achieved with a median TI duration approaching 1 year to imetelstat compared with 13 weeks with the placebo. The median duration for 24 weeks for those on imetelstat was approximately 1.5 years.
For individuals achieving 8-week TI, median increases in hemoglobin were 3.6 g/dL for imetelstat and 0.8 g/dL for the placebo.
Individuals who were on imetelstat also experienced a clinically meaningful and statistically significant mean reduction in red blood cell transfusion units compared with the placebo.
Treatment emergent adverse events (TEAEs) were consistent with the known safety profile of imetelstat from prior clinical trials, and there were no new safety signals identified. The overall treatment discontinuation rates were consistent between both groups at 77.1% for imetelstat and 76.3% for the placebo.
The most common non-hematologic TEAEs for imetelstat included alanine aminotransferase increase, asthenia, COVID-19, diarrhea, headaches, and peripheral edema.
The most frequent hematologic TEAEs were grade 3/4 neutropenia and thrombocytopenia, at 61.9% for imetelstat and 8.5% for the placebo.
Geron announces positive top-line results from IMerge phase 3 trial of imetelstat in lower risk MDS. Business Wire. News release. January 4, 2023. Accessed January 9, 2023. https://www.businesswire.com/news/home/20230104005065/en