- New dynamic analyses of Phase 3 SIMPLIFY-1
transfusion data demonstrate that momelotinib patients are nearly
10-times more likely to remain transfusion free compared to
ruxolitinib treated patients -
VANCOUVER, Nov. 6, 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
new analyses of RBC transfusion data from SIMPLIFY-1, a
double-blind Phase 3 trial of its investigational drug momelotinib
vs ruxolitinib in JAK inhibitor naïve patients, will be presented
in a poster at the 61st American Society of
Hematologists (ASH) Annual Meeting in Orlando, Florida. These retrospective
analyses, to be presented by renowned myelofibrosis expert, Dr.
Ruben Mesa, demonstrate that
patients who received momelotinib had significantly decreased
transfusion requirements compared to those treated with
ruxolitinib, including a decreased risk of receiving a transfusion
and a longer transfusion-free period.
"We explored the relative burden of transfusions, a tangible and
significant concern to clinicians and patients with myelofibrosis,
by examining the SIMPLIFY-1 data comprising more than 400
myelofibrosis patients through statistical models utilizing a
variety of novel dynamic anemia benefit endpoints, including the
proportion of patients who remained transfusion free, the odds of
requiring zero transfusions, the time to first transfusion in
patients who remain transfusion requiring and the overall
transfusion burden," said Dr. Ruben
Mesa, Director of the Mays Cancer Center, home to UT Health
San Antonio MD Anderson Cancer Center. "Overall, these highly
persuasive statistical analyses further confirm that momelotinib
treatment elicits a substantive mechanistically-driven anemia
benefit, including a significantly greater proportion of
momelotinib patients remaining transfusion free, a 50% lower risk
of receiving a transfusion and nearly 10-fold higher odds of
receiving no transfusions during the 24-week study period, directly
compared to ruxolitinib."
Historically, myelofibrosis clinical studies have employed
landmark analyses of transfusion independence or dependence to
describe anemia benefit. While momelotinib is the only JAK
inhibitor to have demonstrated superior head-to-head landmark
anemia benefits compared to ruxolitinib, these static measures of
anemia alone do not fully describe the significant, clinically
meaningful anemia benefit observed following momelotinib
administration. In conjunction with the statistical
consulting group at the International Drug Development Institute
(IDDI), Sierra has developed additional sophisticated dynamic
statistical analyses of anemia benefit in order to complement those
assessments typically presented in the myelofibrosis
literature.
"Chronic, progressive anemia is a key hallmark feature of
myelofibrosis and 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 induce or worsen anemia, exacerbating this
significant unmet medical need in anemic myelofibrosis patients,"
said Dr. Barbara Klencke, Chief
Development Officer of Sierra Oncology. "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 is 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, consistent with momelotinib's pro-erythropoietic
effect.
New retrospective analyses of the SIMPLIFY-1 transfusion data
demonstrated that:
- The Kaplan-Meier (K-M) proportion of patients who did not
require any transfusions during the randomized treatment period was
significantly greater for the momelotinib treated group (73%) than
those who received ruxolitinib (46%; p<0.0001)
- The K-M proportion of patients requiring fewer than 5 RBC units
over the treatment period was also significantly greater for
momelotinib (83%) than ruxolitinib (62%; p<0.0001).
- The odds of a momelotinib patient receiving no transfusions was
approximately 10-fold higher including covariates, compared to a
patient treated with ruxolitinib
- The overall transfusion burden during momelotinib therapy was
approximately half of that for ruxolitinib (HR 0.522; p<0.0001)
for models both with and without baseline characteristics from
patients as covariates.
These dynamic measures of transfusion requirement will be
further evaluated as exploratory endpoints in MOMENTUM, a planned
Phase 3 study of momelotinib in anemic myelofibrosis
patients previously treated with a JAK inhibitor, anticipated
to launch in the fourth quarter of 2019. The MOMENTUM trial
has been designed to re-confirm momelotinib's ability to address
each of the three hallmark features of myelofibrosis, namely
constitutional symptoms, anemia, and splenomegaly. Dr. Srdan
Verstovsek, MD, PhD, Chief, Section for Myeloproliferative
Neoplasms, Department of Leukemia, Division of Cancer Medicine, The
University of Texas MD Anderson Cancer
Center, Houston, Texas, has been
named Chief Investigator of the trial.
About the ASH 2019 Poster:
Title: Dynamic and
Time-To-Event Analyses Demonstrate Marked Reduction in Transfusion
Requirements for Janus Kinase Inhibitor–Naïve Myelofibrosis
Patients Treated with Momelotinib Compared Head to Head with
Ruxolitinib
Session Name: 634. Myeloproliferative Syndromes: Clinical: Poster
I
Date: Saturday, December 7, 2019
Presentation Time: 5:30 PM - 7:30
PM
Location: Orange County Convention
Center, Hall B
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. More than 1,200 subjects have received momelotinib
since clinical studies began in 2009, including more than 800
subjects treated for myelofibrosis. Sierra plans to launch the
MOMENTUM Phase 3 clinical trial in the fourth quarter of 2019 to
support potential registration of momelotinib on a global basis.
Momelotinib is wholly owned by Sierra Oncology and is covered by
patents anticipated to provide potential exclusivity to 2040 in
the United States and Europe (including Patent Term Extension or
Supplementary Protection Certificate).
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 Oncology retains the global commercialization rights to
momelotinib, 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, timing of the
initiation of MOMENTUM, expected timing of the execution of, and
expected results from, non-dilutive strategic options, and
potential benefits of Sierra Oncology's lead product candidate and
other product candidates. 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