Selcodebart improved hemoglobin levels and transfusion independence across 3 anemia cohorts in myelofibrosis, regardless of concomitant JAK inhibitor use.
Selcodebart (DISC-0974), an investigational anti-hemojuvelin antibody, produced hematologic responses across 3 anemia-defined cohorts of patients with myelofibrosis, according to initial efficacy data from the phase 1/2 RALLY-MF trial (NCT05320198) presented at the
At a data cutoff of April 27, 2026, 55% of evaluable non–transfusion-dependent patients (n = 31) achieved a mean hemoglobin level increase of 1.5 g/dL sustained for 12 weeks or longer, 64% of patients with low transfusion dependence (n = 11) achieved transfusion independence for at least 16 weeks, and 50% of patients with high transfusion dependence (n = 8) achieved transfusion independence for at least 12 weeks. Responses occurred regardless of concomitant JAK inhibitor use; 56% of patients receiving a JAK inhibitor (n = 25) and 56% of those not receiving one (n = 25) achieved a major hematologic response.
Elevated hepcidin levels are considered a key driver of myelofibrosis-related anemia; levels run higher in patients with myelofibrosis-related anemia than in healthy control patients, and these levels track with anemia severity and transfusion burden.² No therapy is currently FDA approved specifically for this indication, and JAK inhibitor use can itself worsen anemia, according to the RALLY-MF study authors.1 Selcodebart blocks the co-receptor hemojuvelin, interrupting bone morphogenetic protein–SMAD signaling in the liver to reduce hepcidin production, mobilize stored iron into circulation, and increase iron absorption and hemoglobin levels.
RALLY-MF enrolled adult patients with primary myelofibrosis, post–essential thrombocythemia myelofibrosis, or post–polycythemia vera myelofibrosis with anemia, excluding anemia attributable to infection, bleeding, or iron or vitamin B12 deficiency. Patients were assigned to the following subgroups: non–transfusion-dependent (baseline hemoglobin levels less than 10 g/dL without transfusion), low transfusion dependent (requiring 1-2 packed red blood cell [PRBC] units over 84 days), or high transfusion dependent (requiring 3-12 PRBC units over 84 days) cohorts. The use of concomitant stable JAK inhibitor or hydroxyurea was permitted. Selcodebart was dosed subcutaneously at 50 mg every 28 days for 6 cycles, with escalation to 75 mg at day 57 for insufficient response, followed by an optional continuation period. As of the data cutoff, 61 patients had been treated (non–transfusion-dependent, n = 35; low transfusion dependent, n = 13; high transfusion dependent, n = 13), with 50 total patients evaluable for efficacy.
RALLY-MF Trial: Highlights
Among evaluable non–transfusion-dependent patients, the mean time to major response was 27 ± 30 days (n = 17), and the mean duration of the longest major response through the optional continuation phase was 318 (standard deviation [SD], 235) days (n = 14). Among evaluable patients with low transfusion dependence, the mean time to major response was 4 (SD, 8) days (n = 7), and the mean duration of the longest major response through the optional continuation phase was 345 (SD, 243) days (n = 6). Among evaluable patients with high transfusion dependence, the mean time to major response was 2 (SD, 1) days (n = 4), and the mean duration of the longest major response through the optional continuation phase was 239 (SD, 18) days (n = 2).
Hepcidin reduction, iron mobilization, and hematologic response outcomes were similar regardless of concomitant JAK inhibitor therapy, including ruxolitinib (Jakafi), momelotinib (Ojjaara), and pacritinib (Vonjo).
Both non–transfusion-dependent and low transfusion dependent patients reported clinically meaningful improvements on the FACIT-Fatigue scale, exceeding the established 3-point threshold for clinical significance. Improvement in FACIT-Fatigue score correlated with hemoglobin level change at end of study (P = .0120). Improvement in Patient Global Impression of Severity also correlated with hemoglobin level change (P = .0004). Additionally, 50% of –transfusion-dependent and low transfusion dependent patients with major responses achieved a 50% reduction in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score by end of study.
Any treatment-emergent adverse effects (TEAEs) occurred in 56 of 61 evaluable patients (91.8%), with treatment-related TEAEs seen in 24.6% of patients, serious AEs observed in 19.7% of patients, grade 3 or higher TEAEs reported in 41.0% of patients, and AEs of special interest seen in 3.3% of patients (n = 2; both related to decreased renal function). The most common TEAEs seen in more than 10% of patients included muscle spasms (21.3%); diarrhea and fatigue (16.4% each); anemia and headache (14.8% each); and dizziness, urinary tract infection, and falls (13.1% each). One patient discontinued treatment because of AEs (nephrolithiasis, chronic kidney disease, and Clostridium colitis), none of which were considered related to selcodebart.
The investigators noted that RALLY-MF is a single-arm study, with follow-up ongoing in the non–transfusion-dependent cohort and enrollment ongoing in the transfusion-dependent cohorts.
