The Lancet Publishes Geron’s Phase 3 Results in Lower Risk MDS

Rare Daily Staff

Geron said The Lancet published positive results from the IMerge phase 3 trial investigating imetelstat versus placebo in patients with lower risk myelodysplastic syndromes.

The study was in MDS patients who were relapsed/refractory or ineligible for erythropoiesis stimulating agents. The publication is available online and will be available in print at a later date.

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 under regulatory review by the FDA and by the European Medicines Agency 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 erythropoiesis stimulating agents.

In the IMerge phase 3 clinical trial, the primary endpoint of red blood cell transfusion independence (TI) for at least eight consecutive weeks was significantly higher with imetelstat vs. best supportive care, with median TI duration approaching one year for imetelstat eight-week TI responders.

Mean hemoglobin levels in imetelstat-treated patients increased significantly 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.

Patient-reported outcomes 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 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.

“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, executive vice president and chief medical officer of Geron. “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.”

Photo: Faye Feller, executive vice president and chief medical officer of Geron