On December 7, 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 new analyses of Phase 3 clinical data highlighting the anemia related benefits of momelotinib directly compared to ruxolitinib, which were presented at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida (Press release, Sierra Oncology, DEC 7, 2019, View Source [SID1234552030]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Transfusion dependency and moderate to severe anemia are the most important negative prognostic factors for overall survival in myelofibrosis," said Dr. Ruben Mesa, Director of the Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center. "These novel analyses of RBC transfusion data from the Phase 3 SIMPLIFY-1 study further demonstrate momelotinib’s compelling anemia benefits, including a substantively reduced transfusion burden compared directly with ruxolitinib, and further support momelotinib as a potentially desirable treatment option for patients with myelofibrosis."
"These retrospective analyses, performed using a variety of novel dynamic anemia benefit endpoints, underscore the demonstrably lower burden of transfusions experienced by myelofibrosis patients treated with momelotinib versus ruxolitinib in a large, blinded, randomized, clinical trial," said Dr. Nick Glover, President and CEO of Sierra Oncology. "Momelotinib uniquely inhibits ACVR1 in addition to JAK1 and JAK2, resulting in an array of distinct and clinically relevant mechanistically-based anemia benefits. While momelotinib’s favorable effect on anemia was previously demonstrated in direct comparison to ruxolitinib using a variety of standard landmark analyses of data from SIMPLIFY-1, these new analyses further describe the relative patient burden of transfusions on study, and help contrast the differences in therapeutic options for clinicians."
"Transfusion burden is a fundamental consideration in myelofibrosis, a disease characterized by chronic, progressive anemia. Specifically, preventing transfusions for patients who are currently transfusion free, or reducing or eliminating the need for transfusions for patients who are actively receiving regular blood transfusions are clinically important outcomes of direct relevance to myelofibrosis patients and their clinicians, underscoring the importance of these data," said Dr. Barbara Klencke, Chief Development Officer of Sierra Oncology. "Myelofibrosis is a disease comprising three clinical dimensions – constitutional symptoms, anemia and splenomegaly. Critically, momelotinib’s meaningful anemia benefits were achieved while also maintaining clinically comparable benefits on splenomegaly and constitutional symptoms as directly compared to ruxolitinib."
The new analyses demonstrate that:
Patients who received momelotinib had significantly decreased transfusion requirements compared to those treated with ruxolitinib, including a nearly 10-fold higher odds of receiving no transfusions during the 24-week study period (covariate ZINB model; p < 0.0001).
Patients receiving momelotinib had a significantly reduced chance of receiving one transfusion, two ‘transfusion events’ (≥ 3 RBC units) or three ‘transfusion events’ (≥ 5 RBC units).
At any given time, the mean cumulative number of RBC units received for a typical patient receiving momelotinib is approximately half of that for patients receiving ruxolitinib (HR = 0.522; p < 0.0001). Thus, for patients on momelotinib, half as many RBC units are transfused at any time as compared to ruxolitinib.
A Kaplan-Meier time-to-first RBC unit transfused analysis indicated an immediate and sustained momelotinib treatment effect compared to ruxolitinib (log-rank p < 0.0001).
A sustained and durable period of transfusion independence (TI) was maintained over long-term treatment on momelotinib. The median time to loss of TI was not reached for momelotinib-treated patients, with a follow up period exceeding 3 years.
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.
Sierra management will host an Analyst & Investor Event on Sunday, December 8th at 7:00 am ET to discuss these results. The event will include a presentation by renowned myelofibrosis expert, Dr. Ruben Mesa, Director of the Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center.
Sierra recently launched the MOMENTUM Phase 3 clinical trial, 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.
About Momelotinib
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 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.
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).
Analyst and Investor Event and Webcast Information
Sierra Oncology will host an Analyst & Investor Event to discuss these data being presented at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida. The event will be led by Dr. Nick Glover, President and CEO of Sierra Oncology, and include a presentation by Dr. Ruben Mesa.
Date and Time: Sunday, December 8th at 7:00 – 8:00 am ET
Location: Bayhill 33 Meeting Room, Hyatt Regency, 9801 International Dr., Orlando
Event registration and webcast information are available through the Sierra Oncology website at www.sierraoncology.com. The event will be webcast live, and an archive of the presentation will be accessible after the event through the Sierra Oncology website.
Domestic (Toll Free- US): 1 (844) 467-7642
International (Toll): 1 (417) 385-2994
Conference ID: 3577956
Webcast: www.sierraoncology.com
Direct link: View Source
ASH 2019 Momelotinib Poster Presentation Information:
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 7th, 2019
Presentation Time: 5:30 pm – 7:30 pm ET
Location: Orange County Convention Center, Hall B
The poster will be available on Saturday, December 7th, 2019 on the company’s website at www.sierraoncology.com