- MOMENTUM trial designed to confirm the unique
benefits of momelotinib on all three hallmarks of myelofibrosis:
symptoms, anemia and enlarged spleen -
- Targeting enrollment of 180 symptomatic and anemic patients
previously treated with a JAK inhibitor –
- Top-line data anticipated in Q4 2021 -
VANCOUVER, Nov. 20, 2019 /CNW/ - Sierra Oncology, Inc.
(Nasdaq: SRRA), a late-stage drug development company focused on
the development and commercialization of momelotinib, a JAK1, JAK2
& ACVR1 inhibitor with a potentially differentiated therapeutic
profile for the treatment of myelofibrosis, today announced that it
has launched the MOMENTUM clinical trial for patients with
myelofibrosis. The randomized double-blind global Phase 3 trial is
designed to confirm the efficacy of momelotinib on myelofibrosis
symptoms, transfusion independence and splenomegaly, as compared to
danazol. The trial is targeting enrollment of 180 myelofibrosis
patients who are symptomatic, anemic and have been treated
previously with a JAK inhibitor.
"I am pleased to act as Chief Investigator for this important
global trial for the myelofibrosis patient community," said Dr.
Srdan Verstovsek, MD, PhD, Professor in the Department of Leukemia
at The University of Texas MD Anderson Cancer
Center, Houston, Texas. "JAK
inhibitors remain the cornerstone of myelofibrosis treatment but
new options in this class are needed for the majority of patients
who have difficulty tolerating the currently approved agents due to
the cytopenias they can exacerbate or induce. Momelotinib could
become a suitable alternative for many patients previously treated
with a JAK inhibitor due to its ability to positively address all
three hallmarks of myelofibrosis - symptoms, anemia and an enlarged
spleen. Critically, momelotinib has consistently demonstrated
positive anemia benefits in its prior clinical trials. This anemia
benefit is biologically-driven, via potent inhibition of the
ACVR1/hepcidin axis, a mechanism that is unique in the JAK
inhibitor class."
"The launch of the MOMENTUM trial is a key milestone in our
global registration strategy for momelotinib, aimed at bringing
this important and differentiated therapy to patients with
myelofibrosis," said Dr. Barbara
Klencke, Chief Development Officer of Sierra Oncology.
"MOMENTUM is designed to confirm the array of benefits observed in
prior Phase 3 studies, where momelotinib demonstrated a unique
ability to improve anemia and reduce transfusion dependency in
patients with myelofibrosis, while also providing clinically
comparable benefits on constitutional symptoms and enlarged spleens
to other JAK inhibitors. To support our proposed study timeline,
global clinical trial sites are anticipated to be activated over
the coming months with top-line data from MOMENTUM anticipated in
the fourth quarter of 2021."
"The launch of MOMENTUM is a major step in advancing Sierra's
vision of becoming a commercial company. Momelotinib is a promising
late stage asset that targets a sizable unaddressed global market
with a clear path forward to registration. Importantly,
momelotinib's clinical potential has been previously demonstrated
in two large, completed Phase 3 clinical trials, which informed the
design of MOMENTUM," said Dr. Nick
Glover, President and CEO of Sierra Oncology. "As recently
announced, Sierra has secured capital that we expect to be
sufficient to execute our development strategy into the second half
of 2022, providing us with the financial runway to advance
momelotinib towards its anticipated commercialization. Moreover, we
also recently announced that we had amended our Asset Purchase
Agreement (the "Amendment") with Gilead Sciences, Inc. ("Gilead").
Pursuant to the terms of the Amendment, and subject to certain
conditions, Gilead will become a stockholder in Sierra in exchange
for substantive reductions in the annual royalty rates payable by
Sierra to Gilead upon commercialization of momelotinib. This
Amendment will meaningfully benefit Sierra's stockholders should
momelotinib prove commercially successful."
About Momelotinib
Momelotinib is a potent, selective
and orally-bioavailable JAK1, JAK2 & ACVR1 inhibitor with a
differentiated therapeutic profile in myelofibrosis encompassing
robust constitutional symptom improvements, a range of meaningful
anemia benefits, including eliminating or reducing the need for
frequent blood transfusions, and comparable spleen control to
ruxolitinib. More than 1,200 subjects have received momelotinib
since clinical studies began in 2009, including more than 800
patients treated for myelofibrosis.
Chronic, progressive anemia is a key hallmark of myelofibrosis
and transfusion dependence is the most important negative
prognostic indicator of reduced survival in this disease.
Approximately 60% of patients are anemic and 45% are transfusion
dependent within one year of diagnosis, with most patients
ultimately progressing to transfusion dependency. Unfortunately,
currently approved JAK inhibitor therapies can induce or worsen
anemia, exacerbating this significant unmet medical need in anemic
myelofibrosis patients.
The marked systemic inflammation seen in myelofibrosis leads to
increased ACVR1 activity which in turn increases secretion of
hepcidin, resulting in perturbed iron homeostasis and an
iron-restricted anemia. Momelotinib's inhibition of ACVR1 in
addition to JAK1 and JAK2, unique amongst the JAK inhibitor class,
results in notable reductions of both hepcidin and inflammation,
restoring iron homeostasis and RBC production, thereby alleviating
anemia and transfusion dependency.
The SIMPLIFY-1 trial was a double-blind, active-controlled Phase
3 study in which 432 patients received randomized treatment with
momelotinib or ruxolitinib for 24 weeks (JCO. 2017;35:3844–50). In
addition to a significant reduction in splenomegaly and
improvements in constitutional symptoms, previously reported
analyses of the SIMPLIFY-1 data demonstrated that patients in the
momelotinib arm achieved nominal-statistical significance for all
anemia endpoints tested, including a higher rate of transfusion
independence (p < 0.001) and lower rates of transfusion
dependence (p = 0.019) at Week 24, compared to patients on
ruxolitinib.
Retrospective analyses of SIMPLIFY-1 transfusion data, to be
presented in a poster at ASH 2019, demonstrate that the odds of
momelotinib patients remaining transfusion free are nearly 10-times
higher than those for ruxolitinib treated patients.
Momelotinib is an investigational drug that is not approved for
any use in any country. The U.S. Food and Drug Administration has
granted Fast Track designation to momelotinib for the treatment of
patients with intermediate/high-risk myelofibrosis who have
previously received a JAK inhibitor.
Momelotinib is wholly owned by Sierra Oncology and is protected
by patents anticipated to provide potential exclusivity to 2040 in
the United States and Europe (including Patent Term Extension or
Supplementary Protection Certificate).
About the MOMENTUM Phase 3 Clinical Trial for Patients with
Myelofibrosis:
The MOMENTUM Phase 3 clinical trial is a
randomized double-blind trial designed to enroll 180 myelofibrosis
patients who are symptomatic and anemic, and who have been treated
previously with a JAK inhibitor. Patients will be randomized 2:1 to
receive either momelotinib or danazol. Danazol has been
selected as an appropriate treatment comparator given its use to
ameliorate anemia in myelofibrosis patients, as recommended by NCCN
and ESMO guidelines. After 24 weeks of treatment, patients on
danazol will be allowed to crossover to receive momelotinib.
The Primary Endpoint of the trial is the Total Symptom Score
(TSS) response rate of momelotinib compared to danazol at Week 24
(99% power; p-value < 0.05).
Secondary and exploratory endpoints include:
- Transfusion Independence (TI) rate at Week 24 (key secondary:
>90% powered; p-value < 0.05),
- Splenic response rate (SRR) at Week 24 (>90% powered;
p-value < 0.05),
- Duration of TSS response to Week 48,
- Other measures of anemia benefit, including Transfusion
Dependence response rate and various measures of cumulative
transfusion burden,
- Patient Reported Outcome measures of fatigue and physical
function.
About Sierra Oncology
Sierra Oncology is a late stage
drug development company focused on advancing targeted therapeutics
for the treatment of patients with significant unmet medical needs
in hematology and oncology. Momelotinib, Sierra's lead drug
candidate, is a potent, selective and orally-bioavailable JAK1,
JAK2 & ACVR1 inhibitor with a differentiated therapeutic
profile in myelofibrosis encompassing robust constitutional symptom
improvements, a range of meaningful anemia benefits, including
eliminating or reducing the need for frequent blood transfusions,
and comparable spleen control to ruxolitinib.
Sierra is also developing a portfolio of DNA Damage Response
(DDR) assets, consisting of SRA737 and SRA141, and is conducting a
campaign intended to seek non-dilutive strategic options to support
their further advancement. SRA737 is a potent, highly selective,
orally bioavailable small molecule inhibitor of Checkpoint kinase 1
(Chk1), a key regulator of cell cycle progression and the DDR, and
has demonstrated preliminary clinical efficacy. SRA141 is a potent,
selective, orally bioavailable small molecule inhibitor of Cell
division cycle 7 kinase (Cdc7) with a potential novel mechanism of
cytotoxicity, and has successfully completed the IND process with
the FDA enabling the commencement of clinical trials. Sierra
retains the global commercialization rights to SRA737 and
SRA141.
For more information, please visit www.sierraoncology.com.
Cautionary Note on Forward-Looking Statements
This
press release contains forward-looking statements within the
meaning of the "safe harbor" provisions of the Private Securities
Litigation Reform Act of 1995, including, but not limited to,
statements regarding Sierra Oncology's expectations from current
data, anticipated clinical development activities, the expected
timing of, and results of MOMENTUM, potential benefits of Sierra
Oncology's lead product candidate and other product candidates and
sufficiency of its capital resources. All statements other than
statements of historical fact are statements that could be deemed
forward-looking statements. These statements are based on
management's current expectations and beliefs and are subject to a
number of risks, uncertainties and assumptions that could cause
actual results to differ materially from those described in the
forward-looking statements. Such forward-looking statements are
subject to risks and uncertainties, including, among others, the
risk that Sierra Oncology may be unable to successfully develop and
commercialize product candidates, product candidates may not
demonstrate safety and efficacy or otherwise produce positive
results, Sierra Oncology may experience delays in the preclinical
and anticipated clinical development of its product candidates,
Sierra Oncology may be unable to acquire additional assets to build
a pipeline of additional product candidates, Sierra Oncology's
third-party manufacturers may cause its supply of materials to
become limited or interrupted or fail to be of satisfactory
quantity or quality, Sierra Oncology's cash resources may be
insufficient to fund its current operating plans and it may be
unable to raise additional capital when needed, Sierra Oncology may
be unable to obtain and enforce intellectual property protection
for its technologies and product candidates and the other factors
described under the heading "Risk Factors" set forth in Sierra
Oncology's filings with the Securities and Exchange Commission from
time to time. Sierra Oncology undertakes no obligation to update
the forward-looking statements contained herein or to reflect
events or circumstances occurring after the date hereof, other than
as may be required by applicable law.
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SOURCE Sierra Oncology