Phase III SIMPLIFY-1/MOMENTUM post hoc analyses: Momelotinib in intermediate-1 vs intermediate-2/high-risk MF

Results from post hoc analyses of the randomized, double-blind, phase III SIMPLIFY-1 (NCT01969838) and MOMENTUM (NCT04173494) trials, evaluating momelotinib in patients with intermediate-1 vs intermediate-2/high-risk myelofibrosis (MF), were presented by Prithviraj Bose at the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE. Analyses focused on the momelotinib arms of the intention-to-treat (ITT) populations (SIMPLIFY-1: intermediate-1, n = 46; intermediate-2/high risk, n = 169; MOMENTUM: intermediate-1, n = 7; intermediate-2/high risk, n = 122). Risk groups were defined using the International Prognostic Scoring System (IPSS) for SIMPLIFY-1 and the Dynamic International Prognostic Scoring System (DIPSS) for MOMENTUM. Week 24 outcomes were summarized descriptively and included spleen volume reduction ≥35% from baseline (SVR35), Total Symptom Score reduction ≥50% from baseline (TSS50), transfusion independence (TI), and dual/triple responses. 

Key data: SVR35 rates at Week 24 were numerically similar in intermediate-1 vs intermediate-2/high-risk groups in SIMPLIFY-1 (26.1% vs 26.6%) and MOMENTUM (28.6% vs 22.1%). In SIMPLIFY-1, TSS50 rates were 39.1% vs 24.9% and TI rates were 82.6% vs 62.1% in the intermediate-1 vs intermediate-2/high-risk subgroups, respectively; in MOMENTUM, TSS50 and TI rates were 57.1% vs 23.0% and 57.1% vs 28.7%, respectively. Triple responses, defined as concurrent SVR35, TSS50, and TI at Week 24, occurred in 10.9% vs 10.1% of intermediate-1 and intermediate-2/high-risk patients in SIMPLIFY-1, respectively, and 28.6% vs 1.6% in MOMENTUM, respectively. Grade ≥3 treatment-emergent adverse event (TEAE) rates were lower in the intermediate-1 vs intermediate-2/high-risk groups in both SIMPLIFY-1 (26.1% vs 38.5%) and MOMENTUM (28.6% vs 54.9%). 

Key learning: These post hoc data support momelotinib as a treatment option across the spectrum of intermediate-1, intermediate-2, and high-risk MF and highlight the potential clinical relevance of initiating therapy before progression to higher-risk disease.