- Imetelstat is currently under regulatory review by the FDA and
EMA for the treatment of transfusion-dependent anemia in adult
patients with lower risk MDS
Geron Corporation (Nasdaq: GERN), a late-stage clinical
biopharmaceutical company, today announced presentations of data
from its IMerge Phase 3 clinical trial evaluating first-in-class
investigational telomerase inhibitor imetelstat in patients with
lower risk myelodysplastic syndromes (MDS), as well as population
analysis of claims data in lower risk MDS. The data were presented
at the American Society of Hematology (ASH) Annual Meeting, taking
place from December 9-12, 2023, in San Diego, CA and virtually as
well as published online in Blood.
“These latest analyses from IMerge Phase 3 presented at ASH
contribute to a growing body of data from the trial, including a
recent publication in The Lancet, which continue to give us
confidence in what we believe is a meaningful clinical benefit with
imetelstat in these lower risk MDS patients,” said Faye Feller,
M.D., Executive Vice President, Geron’s Chief Medical Officer. “If
approved, we believe that the significant improvement in red blood
cell transfusion independence possible with imetelstat could
provide an important new treatment option for many lower risk MDS
patients who suffer from iron overload and low quality of life
associated with transfusion dependence.”
“As we continue to see additional analyses from IMerge Phase 3,
such as these latest presentations at ASH, the clinical attributes
of imetelstat continue to be differentiated, particularly high
RBC-TI response rate, durability of response and the consistency of
effect across MDS subgroups that have historically been very
difficult to treat,” 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 is an IMerge lead investigator.
“Additionally, the safety profile was well-characterized, with
Grade 3/4 neutropenia and thrombocytopenia that were generally
transient, reversible to Grade 2 or less, and clinically
manageable, and most importantly, had few clinical consequences and
did not affect the efficacy of imetelstat.”
Below are the highlights of the 6 company-sponsored
abstracts:
“Efficacy of Imetelstat in Achieving Red Blood Cell Transfusion
Independence Across Different Risk Subgroups in Patients With
Lower-Risk Myelodysplastic Syndromes Relapsed/Refractory to
Erythropoiesis-Stimulating Agents in IMerge Phase 3 Study”
This oral presentation provides a subgroup analysis from IMerge
Phase 3 evaluating RBC-transfusion independence (RBC-TI) rates in
patients treated with imetelstat vs. placebo across different risk
subgroups as defined by International Prognostic Scoring System
(IPSS), revised IPSS (IPSS-R) or IPSS molecular (IPSS-M) risk
profiles. The results showed that imetelstat consistently had
higher RBC-TI response rates than placebo across these different
risk subgroups. Overall, durable 24-week and 1-year RBC-TI
responses were observed with imetelstat in all lower- and
higher-risk subgroups. Reclassifying patients by IPSS-M revealed
that one-third of the patients (4/12) identified as higher-risk
IPSS-M derived 8-week RBC-TI benefit whereas higher-risk subgroups
receiving placebo failed to achieve long-term RBC-TI, regardless of
the risk classification scheme used.
“Impact of Mutational Status on Clinical Response to Imetelstat
in Patients with Lower Risk Myelodysplastic Syndromes in the IMerge
Phase 3 Study”
This poster evaluates the impact of MDS-associated mutations on
clinical efficacy of imetelstat for the 165 of 178 patients for
whom mutation data were available. Results showed that in patients
who had more than one mutation detected at baseline and more than
two mutations at baseline, imetelstat significantly improved the
8-week and 24-week RBC-TI response rates compared with placebo. A
significantly higher percentage of imetelstat-treated than
placebo-treated patients with baseline mutations in SF3B1, a gene
commonly mutated in MDS, achieved 8- and 24-week RBC-TI. RBC-TI
responses in patients receiving imetelstat occurred regardless of
the presence of mutations associated with poor prognosis or the
number of mutations. This analysis suggests clinical benefit of
imetelstat across different molecularly defined subgroups and
independent of the underlying molecular mutation pattern.
“Durable Continuous Transfusion Independence With Imetelstat in
IMerge Phase 3 for Patients With Heavily Transfused Non-Del(5q)
Lower-Risk Myelodysplastic Syndromes Relapsed/Refractory to or
Ineligible for Erythropoiesis-Stimulating Agents”
This poster reports on the patients enrolled in IMerge Phase 3
who achieved one-year or greater continuous RBC-TI response, which
included 17.8% of imetelstat-treated patients (21/118; 95% CI,
11.4-25.9) and 1.7% of patients on placebo (1/60; 95% CI, 0-8.9).
One-year RBC-TIs were achieved by 44.7% of 8-week RBC-TI responders
and 63.6% of 24-week RBC-TI responders. During the one-year or
greater RBC-transfusion-free interval, RBC transfusion burden was
reduced from a baseline range of 4-9 units and hemoglobin improved
a median of 5.2 g/dL. Imetelstat 1-year RBC-TI responders had a
median duration of RBC-TI of 123 weeks (95% CI, 80.4-NE) and no
patients progressed to acute myeloid leukemia (AML). At the time of
data cutoff (May 10, 2023), 13 1-year RBC-TI responders receiving
imetelstat and one patient receiving placebo were ongoing on
treatment. Of the 18 imetelstat one-year responders for whom
mutational data were available, complete elimination of certain
mutational clones was observed in 10 of 18 patients (55.5%) for
whom mutational data were available and 13 (72.2%) achieved greater
than or equal to 50% SF3B1 variant allele frequency (VAF)
reduction, including 7 patients with complete elimination of VAF.
For these one-year RBC-TI responders and consistent with the
overall safety profile for patients on IMerge Phase 3, Grade 3-4
thrombocytopenia and neutropenia occurred in 14 (67%) and 20 (95%)
patients, with a mean duration of 1.78 (1.58) and 2.25 (2.48)
weeks, respectively. 81% of Grade 3-4 neutropenia and 89% of Grade
3-4 thrombocytopenia were reversible to Grade 2 or below within 4
weeks.
“Improvement of Patient-Reported Outcomes Among Heavily
Pretreated Patients With Lower-Risk Myelodysplastic Syndromes and
High Transfusion Burden Treated With Imetelstat on the IMerge Phase
3 Trial”
This abstract published in Blood describes exploratory results
from patient-reported outcomes (PROs) questionnaires used in IMerge
Phase 3. Functional Assessment of Cancer Therapy-Anemia (FACT-An;
55 items) and Quality of Life in Myelodysplasia Scale (QUALMS; 38
items) were the main questionnaires used. Findings consistently
showed that imetelstat-treated patients reported improved fatigue,
dyspnea, and QUALMS composite scores (total and physical burden)
compared to those on placebo. Further, patients treated with
imetelstat did not experience greater deterioration in systemic
symptoms, pain, physical function or bleeding than those on
placebo. These data indicate that, in addition to improving RBC
transfusion burden in patients with LR MDS, imetelstat targets
multiple core symptoms of LR MDS simultaneously, also improving
those respective PROs.
“Characterization and Management of Cytopenias after Imetelstat
Treatment in the IMerge Phase 3 Trial of Patients with Lower-Risk
Myelodysplastic Syndromes (LR-MDS)”
This abstract published in Blood describes treatment-emergent
adverse events (TEAEs) of grade 3 or 4 thrombocytopenia and
neutropenia, which were more prevalent in cycles 1-3 (68.6% and
62.7% respectively), and their frequency decreased over time. In
the imetelstat group, cytopenias were managed with
protocol-specified treatment delays and dose adjustments. Dose
reductions due to neutropenia and thrombocytopenia occurred in
33.1% and 22.9% of patients, respectively. Thrombocytopenia and
neutropenia were also managed by cycle delays in 46.6% and 50.8% of
patients, by platelet transfusions in 17.8% of patients, and by
concomitant therapy with growth factor support (mostly during
cycles 2-4) in 34.7% of patients. Among 47 patients who achieved
the primary endpoint of 8-week RBC-TI with imetelstat, 72.3% and
59.6% of patients had grade 3 or4 neutropenia and thrombocytopenia,
respectively. This analysis shows that these Grade 3or 4
thrombocytopenia and neutropenia were generally transient,
reversible and manageable through treatment delays and dose
adjustments, and suggests that these TEAEs do not affect the
efficacy of imetelstat.
A Geron-sponsored population analysis of claims data also were
presented in poster format.
“Durable Transfusion Independence in Lower Risk Myelodysplastic
Syndrome (LR MDS) Is Associated with Better Survival: A Population
Level Analysis Based on a Large US Health Insurance Claims
Database”
This poster describes a population level analysis of 5,662 lower
risk MDS patients identified through Optum Clinformatics® between
October 2015 and June 2022. In these patients, real-world
progression-free survival (rwPFS) from the start of first- and
second- line therapy respectively, was significantly longer in
patients who achieved 16-week RBC-TI after treatments than in
patients who did not (p < .0001). RBC-TI responders also had
significantly greater improvement in median overall survival (OS)
from first and second line than non-responders (p < .0001 for
both). This analysis indicates that achievement of RBC-TI was
associated with improved survival, suggesting that transfusion
dependence is a modifiable predictor of clinical outcomes in lower
risk MDS.
The presentation and posters are available on the Publications
Section of Geron’s corporate website and the abstracts are
available online in Blood.
About IMerge Phase 3
The Phase 3 portion of the IMerge Phase 2/3 study is a
double-blind, 2:1 randomized, placebo-controlled clinical trial to
evaluate imetelstat in patients with IPSS Low or Intermediate-1
risk (lower risk) transfusion dependent MDS who were relapsed
after, refractory to, or ineligible for, erythropoiesis stimulating
agent (ESA) treatment, had not received prior treatment with either
a HMA or lenalidomide and were non-del(5q). To be eligible for
IMerge Phase 3, patients were required to be transfusion dependent,
defined as requiring at least four units of packed red blood cells
(RBCs), over an eight-week period during the 16 weeks prior to
entry into the trial. The primary efficacy endpoint of IMerge Phase
3 is the rate of red blood cell transfusion independence (RBC-TI)
lasting at least eight weeks, defined as the proportion of patients
without any RBC transfusion for at least eight consecutive weeks
since entry to the trial (8-week RBC-TI). Key secondary endpoints
include the rate of RBC-TI lasting at least 24 weeks (24-week
RBC-TI), the duration of RBC-TI and the rate of hematologic
improvement erythroid (HI-E), which is defined under 2006 IWG
criteria as a rise in hemoglobin of at least 1.5 g/dL above the
pretreatment level for at least eight weeks or a reduction of at
least four units of RBC transfusions over eight weeks compared with
the prior RBC transfusion burden. A total of 178 patients were
enrolled in IMerge Phase 3 across North America, Europe, Middle
East and Asia.
About Imetelstat
Imetelstat is a novel, first-in-class investigational telomerase
inhibitor exclusively owned by Geron and being developed in
hematologic malignancies. Data from non-clinical studies and
clinical trials of imetelstat provide strong evidence that
imetelstat targets telomerase to inhibit the uncontrolled
proliferation of malignant stem and progenitor cells in myeloid
hematologic malignancies resulting in malignant cell apoptosis and
potential disease-modifying activity. Imetelstat has been granted
Fast Track designation by the U.S. Food and Drug Administration for
both the treatment of adult patients with transfusion dependent
anemia due to Low or Intermediate-1 risk MDS that is not associated
with del(5q) who are refractory or resistant to an erythropoiesis
stimulating agent, and for adult patients with Intermediate-2 or
High-risk myelofibrosis (MF) whose disease has relapsed after or is
refractory to janus associated kinase (JAK) inhibitor treatment.
Imetelstat is currently not approved by any regulatory
authority.
About Geron
Geron is a late-stage clinical biopharmaceutical company
pursuing therapies with the potential to extend and enrich the
lives of patients living with hematologic malignancies. Our
first-in-class investigational telomerase inhibitor, imetelstat,
harnesses Nobel Prize-winning science in a treatment that may alter
the underlying drivers of disease. The New Drug Application (NDA)
for imetelstat for the treatment of transfusion dependent anemia in
adult patients with lower risk myelodysplastic syndromes (LR MDS)
who have failed to respond or have lost response to or are
ineligible for erythropoiesis-stimulating agents (ESAs), based on
the results from the Phase 3 IMerge clinical trial, is currently
under review by the United States Food and Drug Administration
(FDA) with a Prescription Drug User Fee Act (PDUFA) target action
date of June 16, 2024. In addition, an MAA is under review in the
European Union for the same proposed indication. Furthermore, Geron
currently has an ongoing pivotal Phase 3 clinical trial evaluating
imetelstat in relapsed/refractory myelofibrosis (MF). To learn
more, visit www.geron.com or follow us on LinkedIn.
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: (i) that data from the IMerge Phase 3
clinical trial presented at ASH continue to suggest a meaningful
clinical benefit with imetelstat in patients with lower risk MDS,
and that if approved, imetelstat could provide an important new
treatment option for many lower risk MDS patients; (ii) that, with
additional analyses from IMerge Phase 3, such as the latest
presentations at ASH, the clinical attributes of imetelstat
continue to be differentiated; (iii) that data from IMerge Phase 3
presented at ASH suggests clinical benefit of imetelstat across
different molecularly defined subgroups and independent of the
underlying molecular mutation pattern; (iv) that data from a large
U.S. health insurer claims database presented as ASH indicates that
achievement of RBC-TI was associated with improved survival,
suggesting that transfusion dependence is a modifiable predictor of
clinical outcomes in lower risk MDS; (v) that data from a
patient-reported outcomes (PROs) study presented at ASH indicate
that, in addition to improving RBC transfusion burden in patients
with LR-MDS, imetelstat targets multiple core symptoms of LR-MDS
simultaneously, also improving those PROs; (vi) that data presented
at ASH shows that Grade 3 or 4 thrombocytopenia and neutropenia
experienced by imetelstat-treated patients were generally
transient, reversible and manageable through treatment delays and
dose adjustments, and suggests that these TEAEs do not affect the
efficacy of imetelstat; 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
regulatory authorities permit the further development of imetelstat
on a timely basis, or at all, without any clinical holds; (b)
whether any future safety or efficacy results cause the
benefit-risk profile of imetelstat to become unacceptable; (c)
whether imetelstat actually demonstrates that it alters the
underlying drivers of disease and has disease-modifying activity in
patients; and (d) whether the FDA and EMA will approve imetelstat
for the treatment of transfusion-dependent anemia in patients with
lower risk MDS. 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 September 30, 2023 and future filings and reports by
Geron. 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231211013386/en/
Aron Feingold Vice President, Investor Relations and Corporate
Communications
Kristen Kelleher Senior Manager, Investor Relations
investor@geron.com media@geron.com
Geron (NASDAQ:GERN)
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