Phase II RALLY-MF trial: DISC-0974 in MF stratified by transfusion dependence

Results from the phase II RALLY-MF (NCT05320198) trial evaluating DISC-0974, an anti-hemojuvelin antibody, in patients with non-transfusion-dependent (nTD; n = 35), low-transfusion-dependent (TD Low; n = 13), or high-transfusion-dependent (TD High; n = 13) myelofibrosis (MF) were presented by Naseema Gangat at the European Hematology Association (EHA) 2026 Congress; Jun 11–14, 2026; Stockholm, SE. The primary endpoints were mean hemoglobin (Hb) increase of 1.5 g/dL from baseline persisting for ≥12 weeks in the nTD group, transfusion independence for ≥16 weeks and Hb ≥7 g/dL in the TD Low group, and transfusion independence for ≥12 weeks and Hb ≥7 g/dL in the TD High group. 

Key data: Overall, 55%, 64%, and 50% of patients in the nTD, TD Low, and TD High groups, respectively, met their primary endpoint. Overall response rates (ORRs) were 68%, 73%, and 88%, with major responses in 55%, 64%, and 50% of patients, respectively. Treatment with DISC-0974 led to hepcidin reduction, iron mobilization, and hematologic response regardless of concomitant Janus kinase inhibitor (JAKi) use. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 37.1%, 46.2%, and 46.2% of patients, respectively; the most common TEAEs of any grade in the overall population were muscle spasms (21.3%), diarrhea (16.4%), fatigue (16.4%), anemia (14.8%), and headache (14.8%). 

Key learning: Treatment with DISC-0974 resulted in clinically meaningful hematologic responses across cohorts, with responses achieved regardless of baseline JAKi therapy or concomitant JAKi use and was generally well tolerated in patients with MF.