- 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.
SOURCE Sierra Oncology