On December 4, 2023 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported publication in The Lancet of results from the IMerge Phase 3 trial investigating imetelstat versus placebo in patients with lower risk myelodysplastic syndromes (MDS) relapsed/refractory or ineligible for erythropoiesis stimulating agents (ESAs) (Press release, Geron, DEC 4, 2023, View Source [SID1234638126]). The publication is available online and will be available in print at a later date.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The Lancet’s publication of our IMerge Phase 3 manuscript is a strong validation of the importance of this study within the field, as well as a powerful way of reaching hematologists and other providers globally with these potentially practice-changing results," said Faye Feller, M.D., Executive Vice President, Geron’s Chief Medical Officer. "Based on the highly differentiated qualities of imetelstat reported in this study, we believe that, if approved by regulatory authorities, imetelstat could substantially improve the treatment paradigm in certain patients with lower risk MDS."

Imetelstat is currently under regulatory review by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for approval in transfusion dependent anemia in patients with lower risk MDS who have failed to respond or have lost response to or are ineligible for ESAs.

"I am pleased with the publication in The Lancet of what I believe are very powerful Phase 3 results with this unique mechanism of action, telomerase inhibition, where we see long-term and durable responses broadly across MDS subgroups. This includes lower risk MDS patients without ring sideroblasts (RS-), ESA-ineligible patients who have high serum EPO levels, and those with high transfusion burden, whose needs are not being met by today’s treatments," said Uwe Platzbecker, M.D., Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, Leipzig University Hospital, Leipzig, Germany, who is the lead author on the manuscript and is an IMerge investigator. "With regards to the safety results, neutropenia and thrombocytopenia were predictable and manageable, with little to no significant clinical consequences. These adverse events commonly occurred in the first three cycles and frequently resolved within two weeks."

As previously reported, in the IMerge Phase 3 clinical trial, the primary endpoint of red blood cell transfusion independence (TI) for at least 8 consecutive weeks was significantly higher with imetelstat vs. best supportive care (placebo) (p<0.001), with median TI duration approaching one year for imetelstat 8-week TI responders. Mean hemoglobin levels in imetelstat-treated patients increased significantly (p<0.001) over time compared to placebo patients. For patients achieving 8-week TI, median increases in hemoglobin were 3.6 g/dL for imetelstat and 0.8 g/dL for placebo. Significant and clinically meaningful efficacy results were achieved across key MDS subgroups irrespective of ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category. Patient-reported outcomes (PRO) data reported a sustained meaningful improvement in fatigue for imetelstat-treated patients vs. placebo. Treatment with imetelstat vs. placebo led to greater reduction in variant allele frequency (VAF) in certain genes commonly mutated in MDS, which was associated with longer TI duration and increase in hemoglobin levels. Consistent with prior imetelstat clinical experience, the most common adverse events were thrombocytopenia and neutropenia that were manageable and of short duration.

Click here to view The Lancet publication.

About IMerge Phase 3

The Phase 3 portion of the IMerge Phase 2/3 study is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower risk) transfusion dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a HMA or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of TI and the rate of hematologic improvement erythroid (HI-E), which is defined under 2006 IWG criteria as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, Middle East and Asia.

About Imetelstat

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.