Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, today announced the submission to the United States Food and Drug Administration (FDA) of a New Drug Application (NDA) for imetelstat for the treatment of transfusion-dependent anemia in adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) who have failed to respond or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs).
“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, M.D., Chairman and Chief Executive Officer. “We are deeply committed to addressing the unmet needs for lower risk MDS patients, who often suffer from transfusion-dependent anemia.”
The NDA submission is based on results from IMerge Phase 3, in which the primary endpoint of 8-week transfusion independence (TI) was significantly higher with imetelstat vs. 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. Further, statistically significant and clinically meaningful efficacy results were achieved across key MDS subgroups: ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category. Safety results were consistent with prior imetelstat clinical experience.
As allowed under imetelstat’s Fast Track designation in lower risk MDS, Geron has requested that the FDA grant Priority Review of the NDA. Under standard practice, Geron expects FDA communication in 60 days whether the NDA was accepted for review and the timeline of such review (i.e., priority or standard). Additionally, based on IMerge Phase 3, Geron expects to submit a Marketing Authorization Application (MAA) in the EU in the second half of 2023.
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.
Imetelstat is a novel, first-in-class 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 MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment. Geron submitted a New Drug Application (NDA) in the U.S. in June 2023 and expects to submit a Marketing Authorization Application (MAA) in the EU in the second half of 2023 in the lower risk MDS indication. Imetelstat is currently not approved by any regulatory authority.
Geron is a late-stage biopharmaceutical company pursuing therapies with the potential to extend and enrich the lives of patients living with hematologic malignancies. Our first-in-class telomerase inhibitor, imetelstat, harnesses Nobel Prize-winning science in a treatment that may alter the underlying drivers of disease. Geron currently has two Phase 3 pivotal clinical trials underway evaluating imetelstat in lower risk myelodysplastic syndromes (LR MDS), and in relapsed/refractory myelofibrosis (MF). To learn more, visit www.geron.com or follow us on LinkedIn.
Use of Forward-Looking Statements
Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such statements, include, without limitation, those regarding: (i) that Geron expects to submit a Marketing Authorization Application in the EU in the second half of 2023; (ii) that imetelstat may alter the underlying drivers of disease and has the potential to demonstrate disease-modifying activity in patients; (iii) that Geron expects FDA communication in 60 days whether the NDA was accepted for review; and (iv) other statements that are not historical facts, constitute forward-looking statements. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (a) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (b) whether any future safety or efficacy results cause the benefit-risk profile of imetelstat to become unacceptable; (c) whether the FDA determines there is necessity to withhold their acceptance of the NDA beyond the 60 days; and (d) whether imetelstat actually demonstrates that it alters the underlying drivers of disease and has disease-modifying activity in patients. Additional information on the above risks and uncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron’s filings and periodic reports filed with the Securities and Exchange Commission under the heading “Risk Factors” and elsewhere in such filings and reports, including Geron’s quarterly report on Form 10-Q for the quarter ended March 31, 2023 and future filings and reports by Geron. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances.