- Longer follow-up data for 1-year transfusion independence (TI) in IMerge Phase 3, which demonstrated statistically significant and clinically meaningful continuous, durable efficacy
- Strong correlation of reduction in MDS-associated mutations with clinical benefits, including TI duration, provides compelling evidence for the potential of disease modification
- Based on PRO data, imetelstat-treated patients were more likely to have sustained meaningful improvement in fatigue, as well as experience such improvement more quickly
- Data support NDA submission which is on track for June 2023 to support potential U.S. commercial launch in first half of 2024
- Virtual Geron-hosted investor event featuring KOL and Company participants planned for June 14 from 8:00-9:30am Eastern Time
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, today announced that five abstracts related to imetelstat, a first-in-class telomerase inhibitor, have been accepted at the European Hematology Association (EHA) Annual Meeting taking place from June 8-11, 2023 in Frankfurt, Germany and virtually. The three EHA abstracts on IMerge Phase 3 data expand upon and further confirm the differentiating qualities of imetelstat that can address current unmet needs for lower risk MDS patients compared to available treatments. In addition, abstracts submitted by Geron collaborators covering a translational analysis from a subset of IMerge Phase 2 patients and imetelstat MF pre-clinical data were accepted for oral and poster presentation, respectively.
“The longer follow-up data for one-year TI and additional analyses from IMerge Phase 3 in lower risk MDS we are presenting at EHA further confirm the unprecedented durability of imetelstat, as well as provide deeper insight into the clinically meaningful benefit/risk profile of imetelstat in these patients,” said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. “The strong correlation of reduction in MDS-associated mutations with clinical benefits observed in these patients provides strong evidence for the potential of disease modification with imetelstat. Further, patient reported outcomes presenting sustained meaningful improvement in fatigue is particularly important as fatigue is a specific concern for lower risk MDS patients, and because improvement in fatigue has not been seen with currently available treatments. Overall, as these analyses are completed and as the data continue to mature, a highly compelling and differentiated profile supporting strong clinical benefit is being reinforced for imetelstat in lower risk MDS.”
IMerge Phase 3 Clinical Data – Lower Risk Myelodysplastic Syndromes (MDS)
Abstract #S165: “Continuous Transfusion Independence with Imetelstat in Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents in IMerge Phase 3”
Oral Presentation on June 9 in session s417 “MPN and MDS: Targeting red cells and platelets” (14:45-16:00 CEST) Presenter: Uwe Platzbecker, MD, University Hospital of Leipzig
The abstract reports top-line results from IMerge Phase 3 with a data cut-off of October 2022 for the primary analysis and January 2023 for ≥1-yr transfusion independence (TI). As reported in January 2023, imetelstat demonstrated statistically significant and clinically meaningful efficacy with robust 8-week TI, 24-week TI, and 1-year TI rates.
With 3 months additional follow-up, 17.8% (21/178) of imetelstat-treated patients versus 1.7% (1/60) of placebo-treated patients achieved 1-year TI (P = 0.002), representing 63.6% of 24-week TI imetelstat responders. The continuous TI for more than one year represents substantial relief from transfusion-associated complications for this lower risk MDS patient population.
As reported in January, 39.8% (47/118) of imetelstat-treated patients versus 15.0% (9/60) of placebo-treated patients achieved the study primary endpoint of 8-week TI (P < 0.001). In addition, the rate of 8-week TI was also significantly higher for imetelstat-treated patients versus placebo-treated patients across MDS subtypes, including in RS negative and RS positive patients. Median TI duration using Kaplan Meier estimates (95% CI) was 51.6 (26.9–83.9) weeks for imetelstat-treated patients versus 13.3 (8.0–24.9) weeks for placebo-treated patients (P < 0.001). Key secondary endpoint of 24-week TI was achieved in 28.0% (33/118) of imetelstat-treated patients versus 3.3% (2/60) of placebo-treated patients (P < 0.001).
New data on variant allele frequency (VAF) reductions were also reported in the abstract. For four genes frequently mutated in MDS, the VAF reductions were greater in patients treated with imetelstat than placebo: SF3B1 (P < 0.001), TET2 (P = 0.032), DNMT3A (P = 0.019) and ASXL1 (P = NS). Furthermore, SF3B1 VAF reduction correlated with longer TI duration in imetelstat-treated patients (P < 0.001). These reductions and correlations, together with the durable and continuous TI observed in the trial, support imetelstat’s disease-modifying potential.
The most common Grade 3/4 adverse events with imetelstat were thrombocytopenia and neutropenia with similar rates of Grade ≥3 bleeding and infections observed on imetelstat and placebo. These cytopenias were of short duration, and >80% resolved to Grade ≤2 within 4 weeks. The abstract also noted no new safety signals were identified in the trial.
Abstract #S164: “Disease Modifying Activity of Imetelstat in Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents in IMerge Phase 3”
Oral Presentation on June 11th in session “s448 MDS biology and translational updates” (11:30 - 12:45 CEST) Presenter: Valeria Santini, MD, University of Florence School of Medicine
As noted in the abstract, a main therapeutic goal in lower risk MDS is to alter disease biology by eradicating malignant clones. MDS-initiating cells carrying cytogenetic abnormalities, mutant alleles, or both and arise from malignant stem and progenitor cells. SF3B1, involved in RNA splicing, and TET2, involved in DNA methylation, are recurrently mutated genes in lower risk MDS., Measuring change in VAF of these genes is used to denote disease burden.
Of the 178 patients enrolled in IMerge Phase 3, 22.0% of imetelstat-treated patients and 21.7% of placebo-treated patients had baseline cytogenetic abnormalities. Cytogenetic response was observed in 34.6% (9/26) of imetelstat treated patients (95% CI=17.2–55.7) versus 15.4% (2/13) of placebo-treated patients (95% CI=1.9–45.5). In addition, imetelstat-treated patients demonstrated a higher rate of ≥50% VAF decreases in SF3B1, TET2, DNMT3A, and ASXL1 mutations as compared with placebo.
Imetelstat-treated patients achieving 8-week TI, 24-week TI, and 1-year TI had higher VAF reductions in SF3B1 and TET2 mutations compared with placebo-treated patients.
Additionally, both 8-week TI and 24-week TI responders on imetelstat had significantly greater VAF reductions in SF3B1 mutation versus non-responders (P