Following positive data from the phase 3 IMerge study of imetelstat, the FDA has received a new drug submission for the agent for the treatment of patients with relapsed or refractory myelodysplastic syndrome.
The FDA has received the submission of a new drug application (NDA) for imetelstat, a novel, first-in-class telomerase inhibitor, for the treatment of transfusion-dependent anemia in adult patients with non-del(5q) lower-risk myelodysplastic syndrome (MDS) that is relapsed or refractory to erythropoiesis stimulating agents (ESAs), according to Geron Corporation.1
Results from the phase 3 IMerge study (NCT02598661) in which the primary end point of 8-week transfusion independence was significantly higher among patients given imetelstat at a rate of 39.8% (95% CI, 30.9%-49.3%) compared with treatment with placebo 15.0% (95% CI, 7.1%-26.6%; P <.001) support the submission of the NDA.2 For imetelstat 8-week transfusion independence responders, the median transfusion independence duration approached 1 year, and in patients treated with imetelstat, mean hemoglobin levels significantly increased (P < .001) vs placebo.
Across key MDS subgroups, including ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category, statistically significant and clinically meaningful efficacy results were achieved. Moreover, safety data were consistent with what has previously been reported with imetelstat.
“This pioneering achievement to submit the first new drug application to the FDA for a telomerase inhibitor reflects the dedication, commitment and teamwork of so many people who believed targeting telomerase could make a significant difference for patients,” said John A. Scarlett, MD, chairman and chief executive officer of Geron Corporation, in the press release.1 “We are deeply committed to addressing the unmet needs for lower risk MDS patients, who often suffer from transfusion-dependent anemia.”
In the phase 3 portion of the double-blind, phase 2/3 IMerge study, patients were enrolled at 77 clinical sites in 17 countries. Patients were required to have IPSS low- or Intermediate-1 risk transfusion-dependent MDS that was relapsed or refractory to, or ineligible for, ESA treatment. Patients must have received no prior treatment with a HMA or lenalidomide (Revlimid) and were required to be non-del(5q) and transfusion dependent.2
Once enrolled, patients were randomly assigned in a 2:1 fashion to receive treatment with intravenous imetelstat at a dose of 7.5 mg/kg or placebo every 4 weeks. Patients were subsequently stratified based on transfusion burden (4-6 units vs > 6 units) and IPSS risk category (low vs intermediate-1).
The primary end point of the trial was the rate of red blood cell transfusion independence lasting at least 8 weeks, and secondary end points included 24-week transfusion independence, transfusion independence duration, hematologic improvement-erythroid, and safety. Investigators also explored changes in variant allele frequency and patient-reported outcomes.
Additional findings from the trial were presented at the 2023 ASCO Annual Meeting and showed that 16-week transfusion independence was also improved at 31.4% (95% CI, 23.1%-40.5%) vs 6.7% (95% CI, 1.9%-16.2%), respectively (P < .001). Twenty-four-week transfusion independence was improved at 28.0% (95% CI, 20.1%-37.0%) vs 3.3% (95% CI, 0.4%-11.5%), respectively (P < .001), and at 1 year, patients experienced respective transfusion independence rates of 13.6% (95% CI, 8.0%-21.1%) and 1.7% (95% CI, 0.0%-8.9%; P = .012).
The company has requested the FDA grant priority review of the NDA and expects the FDA to communicate in 60 days whether the NDA was accepted for review, as well as the timeline of such review. In addition, a Marketing Authorization Application is expected to be submitted in the European Union in the second half of 2023.1