Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, is reporting encouraging results for its telomerase inhibitor, imetelstat, in low-risk patients with myelodysplastic syndrome (MDS). At the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, the company presented data indicating durable transfusion independence for an extended period of time, a significant development for MDS patients.
At the ASCO conference, Geron’s presenters showcased the impressive longterm benefits of their new drug, Imetelstat, on patients with lower-risk MDS. The data revealed that compared with those receiving placebo, patients taking Imetelstat achieved significantly higher rates of transfusion independence, fewer transfusion units, and sustaining increases in hemoglobin levels. With Geron on track to submit their US New Drug Application to the FDA this month, we may see Imetelstat available to lower risk MDS patients in the first half of 2024, bringing invaluable aid to those suffering from this condition.
Immensely exciting results were recently reported from the IMerge Phase 3 study, with imetelstat achieving a highly statistically significant primary endpoint of 8-week transfusion independence (TI). A remarkable 39.8% of imetelstat-treated patients experienced 8 weeks of TI compared to only 15.0% of the placebo group (P<0.001). 83% of these responders had a single continuous period of TI, with a median duration approaching one year.
The secondary endpoint of 24-week TI was also met with high statistical significance, with 28.0% of imetelstat-treated patients and only 3.3% of placebo patients reaching this milestone (P<0.001). These results demonstrate the potential of imetelstat to transform the lives of transfusion dependent MDS patients.
The exciting results of the Imetelstat-treated patients showed promise for those with anemia: their hemoglobin levels increased by a median of 3.6 g/dL, compared to only 0.8 g/dL for the placebo group (P<0.001). What’s more, these patients had a statistically significant (P=0.042) and clinically meaningful decrease in RBC transfusion units, and a whopping 42.4% of the imetelstat-treated patients achieved Hematologic Improvement-Erythroid (HI-E) as per the International Working Group (IWG) 2018 criteria (P<0.001) in comparison to placebo’s 13.3%.
Imetelstat showed remarkably higher 8-week transfusion independence rates across a wide range of lower risk myelodysplastic syndromes (MDS) subgroups. This included positive responses regardless of ring sideroblast status, baseline transfusion burden and International Prognostic Scoring System (IPSS) risk category. These results emphasize how beneficial imetelstat can be for various lower risk MDS patients.
The IMerge Phase 3 results have been exceptionally positive in treating lower-risk MDS patients with symptomatic anemia needing regular transfusions, displaying an unprecedentedly high response rate and response durability.
Dr. Amer Methqal Zeidan, Associate Professor of Internal Medicine (Hematology) and director of hematology Early Therapy Research at Yale School of Medicine and Yale Cancer Center, and one of the IMerge lead investigators, praised the results which can potentially provide them with a novel alternative, especially for those with a high transfusion burden and without ring sideroblasts, who have a great-yet-unmet need. The associated adverse events were proven to be manageable and reversible – a unique and promising treatment option on the horizon.
The safety of imetelstat in IMerge Phase 3 showed no new signals, and adverse events were typically mild. Notably, there were no cases of Hy’s Law or drug-induced liver injury, and the incidence of grade 3 laboratory Test abnormalities was similar between the imetelstat and placebo groups. The most frequent hematologic adverse events were Grade 3-4 thrombocytopenia and neutropenia, however these typically resolved soon after, with over 80% reversing to Grade 2 or lower within four weeks. Additionally, there were no fatal hematologic AEs or cytopenic events, with both infection and bleeding consequences being generally low and even across both groups.
Although some patients required dose modifications due to grade 3-4 neutropenia and thrombocytopenia, less than 15% of patients discontinued treatment with imetelstat due to treatment-emergent adverse events (TEAE). Fortunately, if such a situation arises, it generally follows a prolonged course of treatment, with a median time to discontinuation of 21.1 weeks. This means that more than two-thirds of patients will be able to complete their course of treatment!
Imetelstat treatment showed a reduced variant allele frequency of specific genes commonly mutated in MDS, such as SF3B1, TET2, DNMT3A and ASXL1. Remarkably, decreases of SF3B1 VAF were found to be particularly associated with higher haemoglobin levels and a longer time of therapeutic intervention. Additionally, reductions in TET2, DNMT3A and ASXL1 VAF were also linked to a prolonged duration of treatment, suggesting the potential of imetelstat to modify the disease course.
About IMerge Phase 3
The IMerge Phase 3 study is a unique double-blind, 2:1 randomized, placebo-controlled trial with an impressive 178 patients enrolled from North America, Europe, the Middle East and Asia. The trial is testing the effectiveness of imetelstat in transfusion-dependent patients with IPSS Low or Intermediate-1 risk MDS who had either relapsed after or become refractory or ineligible for erythropoiesis-stimulating agent treatment, had not been previously treated with either a HMA or lenalidomide and did not suffer from a del(5q).
To be eligible, they must require at least four units of packed red blood cells (RBCs) over an eight-week period before entry. The primary endpoint is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks. Other 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).
Geron’s revolutionary new telomerase inhibitor, Imetelstat, is creating a buzz in the hematologic malignancy world. With powerful evidence that Imetelstat is able to target and suppress the proliferation of malignant cells, the U.S. Food and Drug Administration has granted it Fast Track designation for treating adults with Low or Intermediate-1 risk MDS that doesn’t involve del(5q) and Intermediate-2 or High-risk MF that relapsed after or is resistant to JAK inhibitor treatment. Plans are underway to submit a New Drug Application (NDA) to the US in June 2023, and a Marketing Authorization Application (MAA) in the EU during the second half of 2023. All in all, Imetelstat is on the forefront of providing groundbreaking solutions to cancer treatment.
Geron is at the forefront of medical innovation, revolutionizing the way we treat hematologic malignancies. Our cutting-edge telomerase inhibitor, imetelstat, founded on Nobel Prize-winning science, has the potential to completely transform the lives of patients. We are delighted to have two Phase 3 clinical trials in progress, exploring the possibility of imetelstat as treatment for lower-risk myelodysplastic syndromes and relapsed/refractory myelofibrosis.
Use of Forward-Looking Statements
With the potential to demonstrate disease-modifying activity in patients, Geron plans to submit a New Drug Application in the U.S. in June 2023 and a Marketing Authorization Application in the EU in the second half of 2023 for IMerge Phase 3 of imetelstat. However, this endeavor faces a number of challenges, including overcoming the delays and other adverse effects caused by the present effects of the COVID-19 pandemic and/or geopolitical events, obtaining regulatory approval on a timely basis, and raising sufficient additional capital to cover the necessary expenses.
There is also the risk that imetelstat may not demonstrate sufficient safety, efficacy, and clinical benefit to obtain regulatory approval or that the follow-up period of 12 months for the IMerge Phase 3 primary analysis may not be sufficient to demonstrate safety and efficacy. These risks and uncertainties, among others, may have an impacton Geron’s business and business prospects, its financial condition, and the future of imetelstat.