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For the IMerge Phase 2 clinical trial, meaningful and durable transfusion independence reported with a new 1-year TI rate, indicating potential disease-modifying activity of imetelstat treatment
For the IMbark Phase 2 clinical trial, the analyses correlate the potential improvement in overall survival from imetelstat treatment with other clinical benefits observed in the trial, such as fibrosis improvement, as well as symptom and spleen response
Data provide further support of ongoing and planned Phase 3 clinical trials of imetelstat
MENLO PARK, Calif., June 12, 2020 (GLOBE NEWSWIRE) -- Geron Corporation (GERN), a late-stage clinical biopharmaceutical company, today announced that an oral presentation and three poster presentations of new clinical data and analyses related to imetelstat, the Company’s first-in-class telomerase inhibitor, are now available on Geron’s website as well as to participants of the Virtual Edition of the 25th Annual EHA Annual Congress.
Updated Efficacy and Safety Data from IMerge Phase 2 Clinical Trial in Lower Risk Myelodysplastic Syndromes (MDS)
“The EHA presentation reports encouraging continued durability data from the IMerge Phase 2 clinical trial, including a median duration of 8-week transfusion independence of 20 months, which is the longest duration we have reported to date in this trial, and that 29% of patients were transfusion free for more than one year,” said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. “We expect these data to drive further interest of investigators, which will promote enrollment for the ongoing IMerge Phase 3 clinical trial in lower risk MDS.”
Title: Treatment with Imetelstat Provides Durable Transfusion Independence (TI) in Heavily Transfused Non-del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) (Abstract #S183)
The oral presentation reports long-term efficacy and safety data from 38 patients in the IMerge Phase 2 clinical trial, based on a February 4, 2020 cut-off date and a median follow-up of 24 months. IMerge is a two-part Phase 2/3 clinical trial evaluating imetelstat in transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (lower risk MDS), who are relapsed after or refractory to prior treatment with ESAs. The first part of IMerge was designed as a Phase 2, open label, single arm study to assess the efficacy and safety of imetelstat. The primary efficacy endpoint is 8-week TI rate, which is defined as the proportion of patients achieving red blood cell transfusion independence during any consecutive eight weeks since entry into the trial. Secondary endpoints include rate of hematologic improvement-erythroid (HI-E) and duration of TI. Several patients remain on treatment in the IMerge Phase 2 clinical trial.
The conclusions of the oral presentation are as follows:
Meaningful and durable transfusion independence (TI):
° High rates of TI and HI-E: 42% 8-week TI rate and 68% HI-E rate
° Durable TI and HI-E: Median duration of TI is 20 months and median duration of HI-E is 21 months
° TI across multiple patient subtypes: ringed sideroblast positive (RS+) and RS-, high and very high transfusion burden
Potential disease-modifying activity:
° 29% of patients transfusion free for more than 1 year
° 75% of 8-week TI responders had a hemoglobin rise of > 3g/dL from pretreatment level
° Reduction in variant allele frequency (VAF) of SF3B1 mutation correlated with shorter time to TI and duration of TI
No new safety signal identified:
° Reversible cytopenias, without significant clinical consequences were most frequent adverse events
The slide presentation is available on Geron’s website at www.geron.com/r-d/publications.
Ongoing IMerge Phase 3 Clinical Trial
The IMerge Phase 3 clinical trial is a double-blind, randomized, placebo-controlled clinical trial with registration intent. The trial is designed to enroll approximately 170 patients with lower risk transfusion dependent MDS who are relapsed or refractory to an ESA, have not received prior treatment with either a hypomethylating agent (HMA) or lenalidomide and who are non-del(5q). The trial was opened for screening and enrollment in August 2019. As of the end of April 2020, approximately 68% of planned clinical sites for the IMerge Phase 3 trial were open for enrollment. Geron expects to complete patient enrollment by the end of the first quarter of 2021. Under current assumptions, the Company expects top-line results to be available in the second half of 2022.
New Analyses of Data from IMbark Phase 2 Clinical Trial in Intermediate-2 or High-risk Myelofibrosis
“Taken together, we believe the three EHA poster presentations reporting new analyses of IMbark Phase 2 data substantiate the OS outcome observed in IMbark and indicate potential disease-modifying activity of imetelstat in yet another hematologic indication,” said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. “These analyses also provide further support for our planned Phase 3 clinical trial in refractory MF, which is expected to open for enrollment in the first quarter of 2021.”
IMbark was designed as a Phase 2 clinical trial to evaluate two dosing regimens of imetelstat (either 4.7 mg/kg or 9.4 mg/kg administered by intravenous infusion every three weeks) in patients with Intermediate-2 or High-risk myelofibrosis (MF) who have relapsed after or are refractory to prior treatment with a janus kinase inhibitor (JAKi). The co-primary efficacy endpoints for IMbark were spleen response rate, defined as the proportion of patients who achieve a reduction of at least 35% in spleen volume as assessed by imaging, and symptom response rate, defined as the proportion of patients who achieve a reduction of at least 50% in Total Symptom Score (TSS), at 24 weeks. Key secondary endpoints were overall survival (OS) and safety.
Title: Telomerase Activity, Telomere Length and hTERT Expression Correlate with Clinical Outcomes in Higher-Risk Myelofibrosis (MF) Relapsed/Refractory (R/R) to Janus Kinase Inhibitor Treated with Imetelstat (Abstract #EP1098)
The conclusions of the poster are as follows:
Imetelstat achieved dose- and exposure-dependent reduction of telomerase activity and human reverse transcriptase (hTERT) expression level, demonstrating on-target mechanism of action.
Achieving optimal pharmacodynamic (PD) effect in patients treated with imetelstat is correlated with longer OS, as well spleen and symptom response.
Significant dose-dependent reduction in VAF of JAK2, CALR and MPL mutations were observed, indicating that imetelstat has disease-modifying activity by targeting the underlying MF malignant clones.
Treatment with 9.4mg/kg of imetelstat improved clinical outcomes in patients with short telomeres or high hTERT expression level at baseline. The results are consistent with telomere biology in cancer cells and provide evidence for on-target mechanism of action of imetelstat through telomerase inhibition.
This is the first clinical report to systematically evaluate the mechanism of action based PD effect of imetelstat, and its relationship to exposure and clinical benefits.
The poster presentation is available on Geron’s website at www.geron.com/r-d/publications.
Title: Imetelstat Treatment Results in Clinical Benefits, Including Improved Overall Survival, in Patients with Higher-Risk Triple Negative Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitors (JAKI) (Abstract #1101)
The overall conclusion of the poster is that triple negative (TN) patients who are relapsed/refractory to JAKi and treated with 9.4 mg/kg of imetelstat had better clinical outcomes and prolonged overall survival (OS) compared to non-TN patients, suggesting that imetelstat may improve the poor outcomes expected for TN patients. Additional highlights from the poster include:
With 9.4 mg/kg of imetelstat treatment, clinical response rates were higher in TN vs non-TN pts: spleen response rate was 18.8% in TN vs 7.3% in non-TN; and symptom response was 50.0% in TN vs 24.4% in non-TN patients.
Imetelstat treatment at 9.4 mg/kg resulted in significantly longer median OS of 35.9 months for TN patients compared to 24.6 months for non-TN patients.
A majority (94%) of the TN patients enrolled on the study had grade three fibrosis. Higher rate of bone marrow fibrosis improvement was noted in the TN (50%) vs non-TN (39.1%) patients.
TN patients enrolled on the study had short telomere length and high hTERT expression level at baseline, representing a suitable target population for imetelstat, a first-in-class telomerase inhibitor.
The poster presentation is available on Geron’s website at www.geron.com/r-d/publications.
Title: Favorable Overall Survival with Imetelstat Treatment Correlates with Other Clinical Benefits in Intermediate-2 or High-Risk Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitor (Abstract #1107)
The poster reports new analyses of data from all 107 patients in both arms (59 patients in the 9.4 mg/kg arm and 48 patients in the 4.7 mg/kg arm) of the IMbark Phase 2 clinical trial with a data cut-off date of February 19, 2020 and a median follow-up of 41.7 months. As of the data cut-off date, median OS was 28.1 months in the 9.4 mg/kg arm and 19.9 months in the 4.7 mg/kg arm.
The overall conclusion of the poster was that imetelstat showed dose-related improvement in OS in patients who are R/R to JAKi. The survival benefit observed with imetelstat was supported by the trend of correlation with other clinical benefits. Additional highlights from the poster include:
Among 57 patients across both treatment arms that had matching bone marrow samples, 20 patients (35%) had ≥1 degree of bone marrow fibrosis improvement while on study and had a significantly longer OS than those who had worsening bone marrow fibrosis. A similar trend was seen in 29 patients (51%) with stable vs. worsening fibrosis.
Patients who achieved symptom and spleen response at week 24 showed a trend of longer OS compared to patients who did not achieve response.
Transfusion dependency, response to last JAKi, higher baseline neutrophils, lower baseline hemoglobin and platelet values correlated with increased risk of death.
The poster presentation is available on Geron’s website at www.geron.com/r-d/publications.
Planned Phase 3 Clinical Trial in Refractory MF
The planned Phase 3 clinical trial in refractory MF is designed to be an open label 2:1 randomized, controlled trial with registration intent to evaluate imetelstat (9.4 mg/kg administered by intravenous infusion every three weeks) in approximately 320 patients with Intermediate-2 or High-risk MF. Patients eligible for the trial will be required to be refractory to a JAK inhibitor, an inclusion criterion that is planned to be defined as having an inadequate spleen response or symptom response after treatment with a JAK inhibitor for at least six months, including an optimal dose of a JAK inhibitor for at least two months. The control arm is planned to be best available therapy (BAT), excluding JAK inhibitors. The primary efficacy endpoint for the trial is planned to be overall survival (OS). Planned key secondary endpoints include symptom response, spleen response, progression free survival, complete response, partial response, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes. Under current assumptions, the Company expects to complete patient enrollment in the second half of 2022, to conduct an interim analysis in the first half of 2023 and to conduct a final analysis in the first half of 2024. The final analysis for OS is planned to be conducted after more than 50% of the patients planned to be enrolled in the trial have died. An interim analysis of OS is planned to be conducted after approximately 70% of the total projected number of events for the final analysis have occurred. Both the planned interim and final analyses are event driven and could occur on different timelines than currently expected.
Event with Key Opinion Leaders to Discuss EHA Presentations
On June 17, 2020, Geron will be hosting a webcasted event with authors from each respective data presentation from the EHA Annual Congress who will reprise the presentations from EHA. A live, listen-only webcast will be available on the Company’s website at www.geron.com/investors/events. If you are unable to listen to the live call, an archived webcast will be available on the Company’s website for 30 days.
Participants may access the conference call live via telephone by dialing domestically +1 (833) 513-0551 or internationally +1 (647) 689-4209. The conference ID is 1988213.
Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the apoptosis of malignant stem and progenitor cells, which allows potential recovery of normal hematopoiesis. Geron’s imetelstat development program includes two ongoing or planned registration-enabling studies, IMerge, an ongoing Phase 2/3 clinical trial in lower risk myelodysplastic syndromes (MDS), and a planned Phase 3 clinical trial in refractory myelofibrosis (MF) expected to be open for patient screening and enrollment in the first quarter of 2021. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment.
Geron is a late-stage clinical biopharmaceutical company focused on the development and potential commercialization of a first-in-class telomerase inhibitor, imetelstat, in hematologic myeloid malignancies. For more information about Geron, visit www.geron.com.
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) the therapeutic potential of imetelstat, including imetelstat’s potential survival benefit for refractory MF patients; (ii) that for the planned Phase 3 clinical trial in refractory MF, Geron expects to begin patient enrollment in the first quarter of 2021, complete patient enrollment in the second half of 2022, conduct an interim analysis in the first half of 2023 and conduct a final analysis in the first half of 2024; (iii) the design, commencement and conduct of the planned Phase 3 clinical trial in refractory MF; (iv) that imetelstat may have disease-modifying activity; (v) that for IMerge, Geron expects to complete enrollment in the first quarter of 2021 and have top-line results in the second half of 2022; (vi) IMerge’s design, including that IMerge will potentially demonstrate durable transfusion independence; and (vii) 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 the evolving effects of the COVID-19 pandemic and resulting global economic and financial disruptions will materially and adversely impact Geron’s business and business prospects, its financial condition and the future of imetelstat; (b) whether Geron overcomes all of the potential delays and other adverse impacts caused by the evolving effects of the COVID-19 pandemic, and overcomes the clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing and regulatory challenges in order to meet the expected timelines and planned milestones in (ii) and (v) above; (c) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (d) whether imetelstat is demonstrated to be safe and efficacious in clinical trials; (e) whether any future efficacy or safety results may cause the benefit-risk profile of imetelstat to become unacceptable; (f) whether imetelstat actually demonstrates disease-modifying activity in patients; (g) Geron’s need to raise substantial capital in order to complete the development and commercialization of imetelstat, including to meet all of the expected timelines and planned milestones in (ii) and (v) above; (h) whether Geron can accurately project or attain complete enrollment in IMerge, the planned Phase 3 refractory MF trial or any potential future clinical trials of imetelstat, whether due to the evolving effects of the COVID-19 pandemic or otherwise; and (i) whether there are failures or delays in manufacturing sufficient quantities of imetelstat or other clinical trial materials in a timely manner, whether due to the evolving effects of the COVID-19 pandemic or otherwise. 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, 2020. 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.
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