On December 13, 2021 Sierra Oncology, Inc. (NASDAQ: SRRA), a late-stage biopharmaceutical company on a mission to deliver targeted therapies that treat rare forms of cancer, reported data from new retrospective analyses of the Phase 3 SIMPLIFY studies demonstrate baseline ferritin differentially predicts Week 24 Transfusion Independence Response for momelotinib and ruxolitinib in patients with myelofibrosis (Press release, Sierra Oncology, DEC 13, 2021, View Source [SID1234596973]). The data were presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held virtually and in Atlanta, GA December 11-14, 2021.
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Baseline Serum Ferritin Differentially Predicts W24 Transfusion Independence Response for Momelotinib and Ruxolitinib in Patients with Myelofibrosis
Myelofibrosis is characterized by the presentation of constitutional symptoms, splenomegaly and anemia, with the degree of anemia and transfusion dependence being among the most important predictors of overall survival. Dr. Stephen Oh, MD, PhD, Washington University School of Medicine in St. Louis and Siteman Cancer Center, noted how the analyses identified pre-treatment serum ferritin level as the most predictive biomarker for the treatment effect of momelotinib versus ruxolitinib on Week 24 Transfusion Independence Response (TI-R) in the SIMPLIFY-1 (JAK inhibitor-naïve) and SIMPLIFY-2 (JAK-inhibitor experienced) studies.
Key results for SIMPLIFY-1 include:
Ruxolitinib was associated with a significantly greater increase in ferritin levels over time compared with momelotinib, irrespective of baseline ferritin, highlighting the differential treatment impact on serum ferritin between the two agents
Baseline hemoglobin (Hgb), an indicator of anemic status, differentially predicted Week 24 TI-R in patients randomized to momelotinib or ruxolitinib
Baseline ferritin also differentially predicted Week 24 TI-R in patients randomized to momelotinib or ruxolitinib
For patients with baseline ferritin between 90-650 ng/mL, momelotinib-treated patients had a higher Week 24 TI-R rate than ruxolitinib-treated patients [72% vs. 38%, OR 4.21 (95% CI: 2.24, 7.89); p=0.0439]
In patients with baseline Hgb <12 g/dL, baseline ferritin levels provided additional, differential predictive value for Week 24 TI-R
The differential treatment effect between momelotinib and ruxolitinib was highest for anemic patients with baseline ferritin between 90-650 ng/ml
No correlation was observed between baseline ferritin and Week 24 splenic or symptom response rates
Findings from SIMPLIFY-1 were independently confirmed in the JAK inhibitor experienced setting of the SIMPLIFY-2 study, where Hgb and ferritin each differentially predicted Week 24 TI-R in patients randomized to momelotinib or best available therapy (BAT; 88.5% ruxolitinib), and baseline ferritin predicted additional, differential predictive value for Week 24 TI-R in patients with Hgb <12 g/dL. For patients with baseline ferritin between 90-650 ng/mL, momelotinib-treated patients had higher Week 24 TI-R than those treated with BAT [53% vs 22%, OR 2.27 (95% CI: 1.01,12.77); p=0.03099].
These data suggest that ferritin may be useful in treatment decision making in myelofibrosis, especially in patients with anemia and ferritin 90-650 ng/mL, in which momelotinib demonstrates a greater TI effect than ruxolitinib. Future evaluation may be made in forthcoming clinical trials to further examine the correlation between ferritin and TI response.
About Momelotinib
Momelotinib is a selective and orally bioavailable JAK1, JAK2 and ACVR1/ALK2 inhibitor currently under investigation for the treatment of myelofibrosis. Myelofibrosis results from dysregulated JAK-STAT signaling and is characterized by constitutional symptoms, splenomegaly (enlarged spleen) and progressive anemia.
Sierra Oncology is currently awaiting topline results of the MOMENTUM clinical trial, a global, randomized, double-blind Phase 3 study evaluating momelotinib for the treatment of symptomatic and anemic myelofibrosis patients. Top-line data are anticipated by February 2022. Assuming positive data, the company plans to file a New Drug Application with the US Food & Drug Administration (FDA) in the second quarter of 2022. The FDA has granted Fast Track designation for momelotinib.