On November 20, 2019 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, reported that it has launched the MOMENTUM clinical trial for patients with myelofibrosis (Press release, Sierra Oncology, NOV 20, 2019, View Source [SID1234551535]). 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.
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"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 (Free ASH Whitepaper) 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 (Free ESMO Whitepaper) 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.