- Data and analyses highlight the differentiating clinical
benefits of imetelstat treatment observed in both the Phase 2
IMerge and IMbark trials
- Additional clinical analyses and data presented on the
depletion of abnormal clones and disease mutations strongly suggest
that imetelstat has disease-modifying activity
- Biomarker data on reductions in telomerase activity and hTERT
expression correlated with clinical outcomes provides evidence of
on-target activity of imetelstat
- All ten abstracts submitted were accepted for presentation
- Presentations provide further support of ongoing and upcoming
Phase 3 clinical trials of imetelstat
Geron Corporation (Nasdaq: GERN), a late-stage clinical
biopharmaceutical company, today announced that four oral
presentations and six poster presentations containing clinical data
and analyses related to imetelstat, the Company’s first-in-class
telomerase inhibitor, were presented at the 62nd American Society
of Hematology (ASH) Annual Meeting. The presentations are available
at www.geron.com/r-d/publications.
“Our imetelstat presentations at this year’s ASH provide strong
support for our two registration-enabling Phase 3 clinical trials:
IMerge, in lower risk MDS and IMpactMF, in refractory MF,” said
Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. “We
believe the analyses and data from our Phase 2 IMerge and IMbark
trials provide strong evidence of imetelstat’s disease-modifying
activity, as well as clinical benefits of durable transfusion
independence in MDS and improvement in overall survival in MF.”
Lower Risk Myelodysplastic Syndromes (MDS) – Oral
Presentation
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 #658)
The oral presentation reported long-term efficacy, safety and
biomarker 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. Consistent with prior presentations, 42% of
patients achieved >8-week red blood
cell transfusion independence (RBC-TI) with a median duration of 20
months, which is the longest so far reported with any agent in
relapsed/refractory non-del(5q) lower risk MDS. In addition, 29% of
patients were transfusion free more than a year. Reduction in the
SF3B1 mutation, one of the key mutations correlated with
ineffective erythropoiesis in lower risk MDS, correlated with
longer transfusion independence and shorter onset to achieve
transfusion independence. These biomarker data together with the
durability of transfusion independence provide evidence for the
disease-modifying activity of imetelstat. These data were
previously presented at the European Hematology Association (EHA)
Annual Congress in June.
Relapsed/Refractory Myelofibrosis (MF) – Three Oral
Presentations
Title: Potential Disease-Modifying Activity of Imetelstat
Demonstrated By Reduction in Cytogenetically Abnormal Clones and
Mutation Burden Leads to Clinical Benefits in Relapsed/Refractory
Myelofibrosis Patients (Abstract #346)
This oral presentation reported significant dose-dependent
reduction of mutation burden by imetelstat, including complete
elimination of mutations in MF driver and non-driver genes. A
greater than 20% reduction in variant allele frequency by
imetelstat treatment correlated with improved clinical benefits,
including higher rates of spleen and symptom responses, bone marrow
fibrosis improvement and longer overall survival (OS). As concluded
in the presentation, imetelstat demonstrated disease-modifying
activity by targeting malignant clones, improvement in bone marrow
fibrosis and OS.
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 #347)
This oral presentation reported dose-dependent inhibition of
telomerase, as evaluated by reductions in telomerase activity,
human reverse transcriptase (hTERT) levels and telomere length in
patients treated with imetelstat in the IMbark Phase 2 clinical
trial. Analyses of these biomarker data correlated with clinical
responses and longer OS. In addition, dose-dependent reduction in
variant allele frequency of driver mutations was noted, indicating
that imetelstat has disease-modifying activity by targeting the
underlying MF malignant clones. As expected for a telomerase
inhibitor, treatment with imetelstat at 9.4 mg/kg improved clinical
outcomes in patients with shorter telomeres and higher hTERT
expression at baseline. These data are consistent with telomere
biology in cancer cells and provide evidence for on-target
mechanism of action of imetelstat through telomerase inhibition.
These results were previously reported as a poster presentation at
the EHA Annual Congress in June.
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 #53)
This oral presentation reported the correlation of overall
survival results from the IMbark Phase 2 with clinical benefits
observed with imetelstat treatment. The correlation analyses showed
a trend of longer OS in patients who achieved symptom response,
spleen volume reductions ranging from > 10% to > 35%,
and statistically significant improvement in OS in patients with
improved bone marrow fibrosis, in a dose-dependent manner. These
results were previously reported as a poster presentation at the
EHA Annual Congress in June.
Relapsed/Refractory Myelofibrosis (MF) – Three Poster
Presentations
Collectively, these poster presentations described on-target and
disease-modifying activity of the higher dose of imetelstat from
the IMbark Phase 2, and how that relates to better clinical
outcomes, including OS, fibrosis improvement and symptom response,
especially in a subset of patients defined as triple negative MF,
known to have poor outcome.
Title: Correlation Analyses of Imetelstat Exposure with
Pharmacodynamic Effect, Efficacy and Safety in A Phase 2 Study in
Patients with Higher-risk Myelofibrosis Refractory to Janus Kinase
Inhibitor Identified an Optimal Dosing Regimen for Phase 3
Study (Abstract #1283)
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 #3084)
Title: Treatment with Imetelstat Improves
Myelofibrosis-Related Symptoms and Other Patient-Reported Outcomes
in Patients with Relapsed or Refractory Higher-Risk
Myelofibrosis (Abstract #3088)
Myeloproliferative Neoplasms (MPN) – Poster
Presentation
Title: Imetelstat Inhibits Telomerase and Prevents
Propagation of ADAR1-Activated Myeloproliferative Neoplasm and
Leukemia Stem Cells (Abstract #1264)
Collaborators at UC San Diego reported non-clinical data on
hTERT and ADAR1 activity in pre-leukemia stem cells and leukemia
stem cells (LSC). In various lab experiments and animal models,
treatment with imetelstat prevented pre-leukemia stem cells from
evolving into LSCs, suggesting telomerase inhibition may be an
effective strategy for preventing MPN progression.
Two Trials in Progress Poster Presentations – Ongoing IMerge
Phase 3 and Upcoming IMpactMF Phase 3
Title: IMerge: A Phase 3 Study to Evaluate Imetelstat in
Transfusion-Dependent Subjects with IPSS Low or Intermediate-1 Risk
Myelodysplastic Syndromes (MDS) that is Relapsed/Refractory to
Erythropoiesis-Stimulating Agent (ESA) Treatment (Abstract
#3113)
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 transfusion dependent
patients with Low or Intermediate-1 risk myelodysplastic syndromes
(MDS), also referred to as lower risk MDS, who have relapsed after
or are refractory to prior treatment with an erythropoiesis
stimulating agent (ESA). The IMerge Phase 3 is currently enrolling
patients.
The primary endpoint is the rate of red blood cell (RBC)
transfusion independence (TI) for any consecutive period of eight
weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints
include the rate of RBC-TI lasting at least 24 weeks, or 24-week
RBC-TI rate, and the rate of hematologic improvement-erythroid
(HI-E), defined as a reduction of at least four units of RBC
transfusions over eight weeks compared with the prior RBC
transfusion burden.
Title: A Randomized Open-Label, Phase 3 Study to Evaluate
Imetelstat Versus Best Available Therapy in Patients with
Intermediate-2 or High-risk Myelofibrosis (MF) Refractory to Janus
Kinase (JAK) Inhibitor (Abstract #2194)
The IMpactMF Phase 3 clinical trial in refractory MF is a
registration-enabling trial with OS as the primary endpoint.
Approximately 320 patients with Intermediate-2 or High-risk MF will
be randomized to receive either imetelstat or best available
therapy, which will exclude JAK inhibitors. 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.
Geron expects the trial to be open for screening and enrollment
in the first quarter of 2021.
About Phase 2 IMerge and IMbark Trials
The IMerge Phase 2 was an open label, single arm trial to assess
the safety and efficacy of a 7.5 mg/kg dose of imetelstat
administered as an intravenous infusion every four weeks in
transfusion dependent lower risk MDS patients who had relapsed
after or were refractory to prior treatment with ESA. The IMerge
Phase 2 is no longer enrolling patients, and patients remaining in
the treatment phase continue to receive imetelstat treatment, per
investigator discretion.
The IMbark Phase 2 was designed 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. The trial is complete and closed.
About Imetelstat
Imetelstat is a novel, first-in-class telomerase inhibitor
exclusively owned by Geron and being developed in hematologic
myeloid malignancies. Early clinical data strongly suggest that
imetelstat has disease-modifying activity through the apoptosis of
malignant stem and progenitor cells, which allows potential
recovery of normal hematopoiesis. Current clinical studies of
imetelstat include IMerge, an ongoing Phase 2/3 trial in lower risk
myelodysplastic syndromes (MDS), and IMpactMF, an upcoming Phase 3
clinical trial in refractory myelofibrosis (MF). Imetelstat has
been granted Fast Track designation by the United States 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.
About Geron
Geron is a clinical stage 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) imetelstat’s
potential survival benefit for MF patients who have relapsed after,
or are refractory to, prior treatment with a JAKi
(relapsed/refractory MF); (ii) that the analyses and data from
IMbark and IMerge provide strong evidence that imetelstat has
disease-modifying activity, may enable patients to have clinical
benefits of durable transfusion independence in MDS and improvement
in overall survival in MF; (iii) that analyses and data presented
on the depletion of abnormal clones and disease mutations strongly
suggest that imetelstat has disease-modifying activity; 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 whether: (i) imetelstat in clinical
trials is able to demonstrate an overall survival benefit in
patients who have relapsed/refractory MF; (ii) imetelstat
demonstrates disease-modifying activity and durable transfusion
independence in MDS in clinical trials; (iii) regulatory
authorities permit the further development of imetelstat; (iv)
imetelstat is safe and efficacious; and (v) any future efficacy or
safety results cause the benefit-risk profile of imetelstat to
become unacceptable. 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 periodic
reports filed with the Securities and Exchange Commission under the
heading “Risk Factors,” including Geron’s quarterly report on Form
10-Q for the quarter ended September 30, 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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version on businesswire.com: https://www.businesswire.com/news/home/20201207005942/en/
Suzanne Messere Investor and Media Relations investor@geron.com
media@geron.com
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