On March 14, 2024 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company developing investigational first-in-class telomerase inhibitor, imetelstat, to treat hematologic malignancies, reported that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 12 to 2 in favor of the clinical benefit/risk profile of imetelstat for the treatment of transfusion-dependent (TD) anemia in adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs) (Press release, Geron, MAR 14, 2024, View Source [SID1234641163]).
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"We are pleased with the Committee’s decision to recognize the positive clinical benefit/risk profile of imetelstat for the treatment of transfusion-dependent anemia in adult patients with lower-risk MDS. There are few treatment options and significant unmet medical need remains for these patients, particularly among those with difficult-to-treat subtypes of this blood cancer," said Faye Feller, M.D., Geron’s Executive Vice President, Chief Medical Officer. "We believe that imetelstat has the potential to be an important new medicine for patients and look forward to continuing our collaboration with the FDA as they complete their review of our New Drug Application."
The ODAC reviewed the results from the IMerge Phase 3 clinical trial. The primary endpoint of red blood cell transfusion independence (RBC-TI) for at least eight consecutive weeks was significantly higher with imetelstat vs. placebo (p<0.001), with median RBC-TI duration approaching one year for imetelstat ≥8-week RBC-TI responders. In addition, 28% of imetelstat-treated patients compared to 3% on placebo obtained a statistically significant improvement in the key secondary endpoint of at least 24-week RBC-TI. For those patients achieving ≥24-week RBC-TI, the median duration was 80 weeks. Clinically meaningful RBC-TI was achieved across key MDS subgroups irrespective of ring sideroblast (RS) status, baseline transfusion burden and International Prognostic Scoring (IPSS) risk category. Additionally, a sustained increase in mean hemoglobin levels in imetelstat-treated patients was observed over time compared to placebo patients. Consistent with prior imetelstat clinical experience, the most common Grade 3-4 adverse events were thrombocytopenia (62%) and neutropenia (68%) that were generally manageable and of short duration.
The FDA assigned a Prescription Drug User Fee Act (PDUFA) target action date of June 16, 2024 for Geron’s New Drug Application (NDA) for imetelstat for the treatment of TD anemia in adult patients with low- to intermediate-1 risk myelodysplastic syndromes, who have failed to respond, or have lost response to, or are ineligible for ESAs. The ODAC provides the FDA with independent opinions and recommendations from outside medical experts, patients and caregivers, though the recommendations are not binding. Geron plans to commercially launch imetelstat in the U.S. upon potential FDA approval.
About IMerge Phase 3
The Phase 3 portion of the IMerge Phase 2/3 trial 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 hypomethylating agent 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 RBC-TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week RBC-TI), the duration of RBC-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, the Middle East and Asia.
About Imetelstat
Imetelstat is a novel, first-in-class investigational telomerase inhibitor exclusively owned by Geron and being developed by Geron 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. 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 kinase (JAK) inhibitor treatment. Imetelstat is currently not approved by any regulatory authority.