- Analyses pooling data from IMerge Phase 2, Phase 3 and the QTc
substudy suggest patients who were ESA ineligible or who had prior
treatment with luspatercept or lenalidomide experienced clinical
benefit from imetelstat similar to prior results from the IMerge
pivotal trial
- Data from the QTc substudy reinforce imetelstat as a
second-line treatment option for LR-MDS patients with
transfusion-dependent anemia regardless of prior therapies,
including luspatercept and lenalidomide
- A patient-reported outcome analysis from IMerge Phase 3 showed
sustained improvement in fatigue and maintenance of quality of life
and anemia symptoms with imetelstat compared with placebo
Geron Corporation (Nasdaq: GERN), a commercial-stage
biopharmaceutical company aiming to change lives by changing the
course of blood cancer, today announced new analyses presented at
the 66th American Society of Hematology (ASH) Annual Meeting from
the IMerge clinical trial in patients with lower-risk
myelodysplastic syndromes (LR-MDS) with transfusion-dependent
anemia suggesting clinical activity of first-in-class telomerase
inhibitor RYTELO™ (imetelstat) regardless of type or number of
prior therapies, as well as favorable patient-reported outcomes
(PROs).
“These latest IMerge analyses presented at ASH contribute to a
growing body of clinical evidence that support RYTELO as a
second-line option in red blood cell transfusion-dependent
lower-risk MDS, regardless of prior treatments,” said Faye Feller,
M.D., Executive Vice President, Chief Medical Officer of Geron.
“Additionally, the sustained improvement in fatigue observed in the
IMerge Phase 3 patient-reported outcomes population is meaningful
for this progressive disease that is characterized by fatigue.”
“Patients with red blood cell transfusion-dependent lower-risk
MDS often cycle through limited available therapies. The IMerge
data presented at ASH suggesting clinical activity of imetelstat
regardless of prior therapies, offers physicians important clinical
evidence while assessing sequencing of treatments,” said Rami S.
Komrokji, M.D., Vice Chair, Malignant Hematology Department,
Moffitt Cancer Center, an investigator of the IMerge clinical
trial, who presented IMerge results at ASH. “Further, anemia and
fatigue remain two of the most burdensome symptoms of lower-risk
MDS, and patient-reported outcomes such as improvement in fatigue
and maintenance of quality of life and anemia symptoms may inform
treatment choices as we aim to improve outcomes for our
patients.”
“Effect of Prior Treatments on the Clinical Activity of
Imetelstat in Transfusion-Dependent Patients with
Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible
Lower-Risk Myelodysplastic Syndromes”
This oral presentation reported findings from analyses
investigating the effects of prior therapies on the clinical
activity of imetelstat using pooled data from IMerge Phase 2, Phase
3, and the QTc substudy. Of the 226 total imetelstat-treated LR-MDS
patients included in this analysis, 90% had prior treatment with an
erythropoiesis-stimulating agent (ESA), 12% had prior treatment
with lenalidomide, 16% had prior treatment with luspatercept and
10% had prior treatment with a hypomethylating agent (HMA). Across
this pooled population, median imetelstat treatment duration was
33.6 weeks (range: 0.1-260.1 weeks).
Imetelstat clinical activity was observed in the pooled patient
population consistent with that of the IMerge Phase 3 pivotal trial
with regards to safety and critical efficacy measures that include
≥8-week red blood cell transfusion independence (RBC-TI), ≥24-week
RBC-TI, RBC transfusion reduction ≥4 U/8 weeks and hemoglobin rise
≥1.5 g/dL/8 weeks.
The results suggest that patients who were ESA ineligible,
patients who had prior treatment with luspatercept or lenalidomide,
or patients who had prior treatment with ESAs followed by
luspatercept or lenalidomide experienced clinical benefit from
imetelstat treatment similar to that demonstrated in the IMerge
Phase 3 pivotal trial. Patients who had prior treatment with HMAs,
or with ESAs followed by HMAs, showed modest clinical activity with
imetelstat. Overall, while these analyses were limited by the small
number of patients in each group, imetelstat showed clinical
activity regardless of prior ESA response status and regardless of
the number of prior lines of therapy.
“Initial Results from the QTc Substudy of the IMerge Phase 3
Trial Demonstrate Clinically Meaningful Efficacy, Manageable
Safety, and Absence of Proarrhythmic Risk in Patients with
Lower-Risk Myelodysplastic Syndromes Who Received Prior Therapies
Beyond Erythropoiesis Stimulating Agents”
This poster presentation reports initial results from the
ventricular repolarization (QTc) substudy of IMerge conducted per
FDA guidance. This substudy differed from the IMerge Phase 3 trial
in its crossover design, the inclusion of patients with del(5q)
MDS, and by allowing prior lenalidomide and HMA therapy besides
ESAs. The QTc substudy population comprised 53 treated patients
(n=35 imetelstat, n=18 placebo). As of the data cutoff on May 10,
2024, 16 of 18 placebo recipients crossed over to receive
imetelstat. Median treatment duration on imetelstat, including
crossover (n=51) was 29.3 weeks; median duration in the imetelstat
group (n=35) was 37.0 weeks and median duration in the crossover
group (n=16) was 27.9 weeks.
In the total imetelstat population (n=51), 41% of patients
(n=21) achieved ≥8-week RBC-TI, 25% of patients (n=13) achieved
≥24-week RBC-TI, 41% of patients (n=21) achieved hematologic
improvement-erythroid (HI-E) per IWG 2018 criteria, 35% of patients
(n=18) had hemoglobin rises ≥1.5 g/dL lasting ≥8 weeks and 75% of
patients (n=38) had RBC transfusion reductions ≥4 U/8 weeks.
In patients with prior luspatercept, lenalidomide or HMA
(azacitidine or decitabine) treatment, 30% (7/23), 38% (5/13), and
21% (3/14) of patients achieved ≥8-week RBC-TI, and 22% (5/23) 15%
(2/13), and 14% (2/14) achieved ≥24-week RBC-TI, respectively.
Patients treated with imetelstat showed no treatment-related
changes in absolute and change in QTcF nor clinically meaningful
effects on cardiac repolarization compared with placebo.
The poster concludes that in this QTc substudy, imetelstat was
associated with an absence of proarrhythmic risk, durable RBC-TI,
transfusion reduction, clinically meaningful increases in
hemoglobin, and a safety profile comparable to the overall
population of the pivotal Phase 3 IMerge trial. RBC-TI was attained
in imetelstat-treated patients who received prior therapies with
HMA, luspatercept and lenalidomide, supporting the use of
imetelstat in patients with relapsed or refractory LR-MDS
regardless of prior therapies.
“Correlation of Patient-Reported Outcomes with Red Blood Cell
Transfusion Reduction and Rise in Hemoglobin in Patients with
Lower-Risk Myelodysplastic Syndromes in the IMerge Trial”
This poster reports on the exploratory PRO analysis from IMerge
Phase 3, with a data cutoff of October 2022. PROs were assessed
with validated using Functional Assessment of Chronic Illness
Therapy-Fatigue (FACIT-Fatigue), Functional Assessment of Cancer
Therapy-Anemia (FACT-An), and Quality of Life in Myelodysplasia
Scale (QUALMS) questionnaires. Sustained meaningful improvement in
fatigue was defined as a ≥3-point increase in FACIT-Fatigue score
for ≥2 consecutive assessments. The PRO population (n=175) included
all patients in the intent-to-treat population who had
FACIT-Fatigue data at baseline and consisted of 118
imetelstat-treated patients and 57 patients who received
placebo.
In the subgroup analysis, more patients treated with imetelstat
than placebo reported sustained improvement in fatigue regardless
of ring sideroblast (RS) status, prior transfusion burden and
baseline serum EPO levels. Additionally, improvement in fatigue was
seen in more patients who responded to imetelstat versus those who
did not across measures of response including RBC-TI, hemoglobin
rise and transfusion reduction. The QUALMS and FACT-An analyses
suggested that imetelstat maintained QOL and anemia symptoms, while
placebo recipients experienced worsening QOL and anemia
symptoms.
The poster concludes that data from the pivotal IMerge phase 3
trial showed that improvement in fatigue with imetelstat was
associated with reduced transfusion burden and a rise in hemoglobin
and that imetelstat appears to offer the advantage of sustained
RBC-TI benefit while maintaining QOL in patients with LR-MDS with
TD anemia.
The ASH presentations are available on Geron’s website in the
investor section under publications.
About RYTELO™ (imetelstat)
RYTELO™ (imetelstat) is an FDA-approved oligonucleotide
telomerase inhibitor for the treatment of adult patients with
low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with
transfusion-dependent anemia requiring four or more red blood cell
units over eight weeks who have not responded to or have lost
response to or are ineligible for erythropoiesis-stimulating agents
(ESAs). It is indicated to be administered as an intravenous
infusion over two hours every four weeks.
RYTELO is a first-in-class treatment that works by inhibiting
telomerase enzymatic activity. Telomeres are protective caps at the
end of chromosomes that naturally shorten each time a cell divides.
In LR-MDS, abnormal bone marrow cells often express the enzyme
telomerase, which rebuilds those telomeres, allowing for
uncontrolled cell division. Developed and exclusively owned by
Geron, RYTELO is the first and only telomerase inhibitor approved
by the U.S. Food and Drug Administration.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Thrombocytopenia
RYTELO can cause thrombocytopenia based on laboratory values. In
the clinical trial, new or worsening Grade 3 or 4 decreased
platelets occurred in 65% of patients with MDS treated with
RYTELO.
Monitor patients with thrombocytopenia for bleeding. Monitor
complete blood cell counts prior to initiation of RYTELO, weekly
for the first two cycles, prior to each cycle thereafter, and as
clinically indicated. Administer platelet transfusions as
appropriate. Delay the next cycle and resume at the same or reduced
dose, or discontinue as recommended.
Neutropenia
RYTELO can cause neutropenia based on laboratory values. In the
clinical trial, new or worsening Grade 3 or 4 decreased neutrophils
occurred in 72% of patients with MDS treated with RYTELO.
Monitor patients with Grade 3 or 4 neutropenia for infections,
including sepsis. Monitor complete blood cell counts prior to
initiation of RYTELO, weekly for the first two cycles, prior to
each cycle thereafter, and as clinically indicated. Administer
growth factors and anti-infective therapies for treatment or
prophylaxis as appropriate. Delay the next cycle and resume at the
same or reduced dose, or discontinue as recommended.
Infusion-Related Reactions
RYTELO can cause infusion-related reactions. In the clinical
trial, infusion-related reactions occurred in 8% of patients with
MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions
occurred in 1.7%, including hypertensive crisis (0.8%). The most
common infusion-related reaction was headache (4.2%).
Infusion-related reactions usually occur during or shortly after
the end of the infusion.
Premedicate patients at least 30 minutes prior to infusion with
diphenhydramine and hydrocortisone as recommended and monitor
patients for one hour following the infusion as recommended. Manage
symptoms of infusion-related reactions with supportive care and
infusion interruptions, decrease infusion rate, or permanently
discontinue as recommended.
Embryo-Fetal Toxicity
RYTELO can cause embryo-fetal harm when administered to a
pregnant woman. Advise pregnant women of the potential risk to a
fetus. Advise females of reproductive potential to use effective
contraception during treatment with RYTELO and for 1 week after the
last dose.
ADVERSE REACTIONS
Serious adverse reactions occurred in 32% of patients who
received RYTELO. Serious adverse reactions in >2% of patients
included sepsis (4.2%) and fracture (3.4%), cardiac failure (2.5%),
and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of
patients who received RYTELO, including sepsis (0.8%).
Most common adverse reactions (≥10% with a difference between
arms of >5% compared to placebo), including laboratory
abnormalities, were decreased platelets, decreased white blood
cells, decreased neutrophils, increased AST, increased alkaline
phosphatase, increased ALT, fatigue, prolonged partial
thromboplastin time, arthralgia/myalgia, COVID-19 infections, and
headache.
Please see RYTELO (imetelstat) full Prescribing Information,
including Medication Guide, available at
https://pi.geron.com/products/US/pi/rytelo_pi.pdf.
About Geron
Geron is a commercial-stage biopharmaceutical company aiming to
change lives by changing the course of blood cancer. Our
first-in-class telomerase inhibitor RYTELO™ (imetelstat) is
approved in the United States for the treatment of certain adult
patients with lower-risk myelodysplastic syndromes (LR-MDS) with
transfusion-dependent anemia. We are also conducting a pivotal
Phase 3 clinical trial of imetelstat in JAK-inhibitor
relapsed/refractory myelofibrosis (R/R MF), as well as studies in
other hematologic malignancies. Inhibiting telomerase activity,
which is increased in malignant stem and progenitor cells in the
bone marrow, aims to potentially reduce proliferation and induce
death of malignant cells. 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, those regarding: (i) that the IMerge
analyses presented at ASH contribute to a growing body of clinical
evidence that support RYTELO as a second-line option in red blood
cell transfusion-dependent lower-risk MDS, regardless of prior
treatments; (ii) that sustained improvement in fatigue observed in
the IMerge Phase 3 patient-reported outcomes population is
meaningful for this progressive disease that is characterized by
fatigue; (iii) that the IMerge data presented at ASH suggests
clinical activity of imetelstat regardless of prior therapies,
offering physicians important clinical evidence while assessing
sequencing of treatments; (iv) that patient-reported outcomes such
as improvement in fatigue and maintenance of quality of life and
anemia symptoms may inform treatment choices for patients with
lower-risk MDS; and (v) 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 Geron
is successful in commercializing RYTELO (imetelstat) for the
treatment of certain patients with LR-MDS with transfusion
dependent anemia; (b) whether Geron overcomes potential delays and
other adverse impacts caused by enrollment, clinical, safety,
efficacy, technical, scientific, intellectual property,
manufacturing and regulatory challenges in order to have the
financial resources for and meet expected timelines and planned
milestones; (c) whether regulatory authorities permit the further
development of imetelstat on a timely basis, or at all, without any
clinical holds; (d) whether any future safety or efficacy results
of imetelstat treatment cause the benefit-risk profile of
imetelstat to become unacceptable; (e) whether imetelstat actually
demonstrates disease-modifying activity in patients and the ability
to target the malignant stem and progenitor cells of the underlying
disease; (f) that Geron may seek to raise substantial additional
capital in order to continue the development and commercialization
of imetelstat; (g) whether Geron meets its post-marketing
requirements and commitments in the U.S. for RYTELO for the
treatment of certain patients with LR-MDS with transfusion
dependent anemia; (h) whether there are failures or delays in
manufacturing or supplying sufficient quantities of imetelstat or
other clinical trial materials that impact commercialization of
RYTELO for the treatment of certain patients with LR-MDS with
transfusion dependent anemia or the continuation of the IMpactMF
trial; (i) that the projected timing for the interim and final
analyses of the IMpactMF trial may vary depending on actual
enrollment and death rates in the trial; (j) whether Geron stays in
compliance with and satisfies its obligations under its debt and
royalty financing agreements; and (k) whether the EMA will approve
RYTELO for the treatment of patients with LR-MDS with transfusion
dependent anemia and whether the FDA and EMA will approve
imetelstat for other indications on the timelines expected, or at
all. 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, 2024, and subsequent 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/20241210229893/en/
Aron Feingold Vice President, Investor Relations and Corporate
Communications
Kristen Kelleher Associate Director, Investor Relations and
Corporate Communications investor@geron.com media@geron.com
Geron (NASDAQ:GERN)
Historical Stock Chart
From Dec 2024 to Jan 2025
Geron (NASDAQ:GERN)
Historical Stock Chart
From Jan 2024 to Jan 2025
