Primary endpoint of 8-week transfusion independence (TI) significantly higher with imetelstat vs. placebo (P<0.001), with median TI duration approaching one year for imetelstat 8-week TI responders
Statistically significant and clinically meaningful efficacy results achieved across key MDS subgroups: ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category
Safety results consistent with prior imetelstat clinical experience
Reduction in variant allele frequency (VAF) of genes commonly mutated in MDS and their correlation with clinical endpoints support disease-modifying potential of imetelstat
Data support NDA submission which is on track for June 2023 to support potential U.S. commercial launch in first half of 2024
FOSTER CITY, Calif., June 02, 2023--(BUSINESS WIRE)--Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, announced a presentation reporting durable continuous transfusion independence with imetelstat, the Company’s first-in-class telomerase inhibitor, in IMerge Phase 3 lower risk MDS patients. These data were presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL.
"The presentation at ASCO of our IMerge Phase 3 data highlighted the meaningful longer-term duration of transfusion independence with imetelstat compared to placebo, as well as significantly higher rates of TI across MDS subgroups, greater reductions in transfusion units and sustained increases in hemoglobin levels," said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. "With our U.S. New Drug Application based on these data on track to be submitted to the FDA this month, I look forward to the day when imetelstat could be available for lower risk MDS patients in the first half of 2024."
IMerge Phase 3 enrolled lower risk MDS patients who were relapsed after, refractory to, or ineligible for erythropoiesis stimulating agent (ESA) treatment and were transfusion dependent, defined as requiring at least four units of packed red blood cells (RBCs) over an eight-week period. The ASCO presentation reported IMerge Phase 3 results with a data cut-off of October 2022, the same for top-line results reported in January 2023. The primary endpoint of 8-week transfusion independence (TI) was met with high statistical significance (P<0.001) for imetelstat-treated patients (39.8%) vs. placebo (15.0%). Of the imetelstat 8-week responders, 83% had a single continuous TI period. Highly statistically significant (P<0.001; hazard ratio 0.23) durable transfusion independence for 8-week TI responders was achieved with a median TI duration approaching one year for imetelstat, compared to approximately 13 weeks for placebo. The key secondary endpoint of 24-week TI was also met with high statistical significance (P<0.001) for imetelstat-treated patients (28.0%) vs. placebo (3.3%).
Mean hemoglobin levels in imetelstat-treated patients increased significantly (P<0.001) 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. Imetelstat-treated patients also experienced a statistically significant (P=0.042) and clinically meaningful mean reduction in RBC transfusion units compared to placebo. A highly statistically significant (P<0.001) hematologic improvement-erythroid (HI-E) rate was achieved for imetelstat (42.4%) versus placebo (13.3%) using the IWG 2018 criteria for HI-E.
Significantly higher 8-week TI rates were observed with imetelstat vs. placebo across key lower risk MDS subgroups, including ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category, with similar 8-week TI responses seen for imetelstat within each subgroup category.
"The IMerge Phase 3 results are especially encouraging because of the significant unmet need in lower risk MDS patients with symptomatic anemia needing regular red blood cell transfusions, especially with less than half of such patients responding to frontline ESA therapy, and most of those who do respond losing that response in less than two years," said Amer Methqal Zeidan, MBBS MHS, Associate Professor of Internal Medicine (Hematology) and director of hematology Early Therapy Research at Yale School of Medicine and Yale Cancer Center, who presented the data at ASCO and is an IMerge lead investigator. "Based on the IMerge trial results, I believe imetelstat represents an important and novel option for patients with lower risk MDS after ESA failure, particularly in terms of the high response rate, durability of response, significant and sustained hemoglobin increase in responders, the preliminary evidence of disease modification across the mutational spectrum of the disease and considering the manageable and reversible adverse event profile. This potential treatment option is especially important for patients with high transfusion burden and those without ring sideroblasts who have high unmet need."
The safety profile observed with imetelstat in IMerge Phase 3 was consistent with prior clinical experience with no new safety signals. Non-hematologic adverse events (AEs) were generally low grade. No cases of Hy’s Law or drug-induced liver injury were observed, and the incidence of grade 3 liver function test laboratory abnormalities was similar between imetelstat and placebo groups. Grade 3-4 thrombocytopenia and neutropenia were the most frequently reported hematologic AEs and were most often reported during Cycles 1-3. These cytopenias resolved within two weeks, and over 80% of events were reversible to grade 2 or lower within 4 weeks. There were no fatal hematologic AEs or cytopenic events. Clinical consequences of grade 3-4 infection and bleeding were low and similar between imetelstat and placebo groups.