Selcodebart Yields Hematologic Responses in Anemia From Myelofibrosis

Selcodebart (DISC-0974), an investigational, first-in-class anti-hemojuvelin monoclonal antibody, produced meaningful hematologic responses and was generally well tolerated in patients with myelofibrosis and anemia, according to data from the ongoing phase 2 RALLY-MF study (NCT05320198).¹

These initial findings were presented in a poster session at the Society of Hematologic Oncology (SOHO) 2026 Annual Meeting.

What hematologic responses were observed with selcodebart?

Responses were evaluated separately across 3 cohorts defined by baseline transfusion burden. Among evaluable non–transfusion-dependent (nTD) patients (n = 31), 55% achieved a major response, defined as a mean hemoglobin increase of at least 1.5 g/dL sustained for 12 weeks or longer, and the overall response rate (ORR) was 68%. Among evaluable transfusion-dependent (TD) low participants, those who received 1 to 2 units at baseline (n = 11), 64% achieved a major response, defined as transfusion independence for at least 16 weeks with a hemoglobin of at least 7 g/dL, and the ORR was 73%.

Among evaluable TD high patients (3 to 12 units at baseline; n = 8), 50% achieved a major response, defined as transfusion independence for at least 12 weeks with a hemoglobin of at least 7 g/dL, and the ORR was 88%. Responses occurred rapidly, with a mean time to major response of 27 days in the nTD cohort, 4 days in the TD low cohort, and 2 days in the TD high cohort. Responses were durable; among nTD major responders with ongoing follow-up (n = 14), the mean duration of the longest major response was 318 days.

Did concomitant JAK inhibitor therapy affect response?

Major responses were achieved regardless of baseline JAK inhibitor therapy. Among evaluable patients with follow-up through study day 113, 56% of those receiving concomitant JAK inhibitor therapy (n = 25) and 56% of those not receiving concomitant JAK inhibitor therapy (n = 25) achieved a major response. Selcodebart dosing led to a sustained decrease in serum hepcidin and an increase in serum iron in patients regardless of concomitant JAK inhibitor therapy or baseline transfusion requirement. Increases in hemoglobin after selcodebart dosing correlated with improvement in patient-reported outcomes; the change in Functional Assessment of Chronic Illness Therapy (FACIT)–Fatigue score and hemoglobin change were correlated (r = 0.49; P = .0120) at the end of study, and nTD and TD low patients experienced clinically significant improvement in FACIT-Fatigue.

“[Selcodebart] is a very versatile agent. It is able to be efficacious regardless of JAK inhibitor use,” lead study investigator Naseema Gangat, MBBS, a professor of medicine and a consultant in hematology at Mayo Clinic Comprehensive Cancer Center, stated in an interview with CancerNetwork® regarding these data. “In terms of specific JAK inhibitors, we did not see any particular difference in terms of improved responses, so the responses held across whether the patients were on ruxolitinib [Jakafi] vs momelotinib [Ojjaara] or pacritinib [Vonjo].”

What was the safety profile of selcodebart?

Among the 61 patients in the analysis, treatment-emergent adverse events (TEAEs) of any grade occurred in 91.8%, treatment-related TEAEs occurred in 24.6%, serious adverse events (SAEs) occurred in 19.7%, and grade 3 or higher TEAEs occurred in 41.0%. The only treatment-related TEAE occurring in at least 2 patients overall was diarrhea (n = 5), none of which were serious.

SAEs and grade 3 or higher adverse events occurring in more than 1 patient included hypotension (n = 2) and cellulitis (n = 2). Grade 3 or higher and non-serious AEs occurring in more than 1 patient included anemia (n = 7), decreased lymphocyte counts (n = 3), and decreased platelet counts (n = 2). AEs of special interest, those related to a decrease in renal function, occurred in 2 patients (increased blood creatinine, n = 2; chronic kidney disease, n = 1), and none were related to the study drug. One patient withdrew because of AEs that were unrelated to selcodebart.

What is selcodebart, and how was RALLY-MF designed?

Hepcidin, a central regulator of iron homeostasis, is pathologically elevated in patients with myelofibrosis and anemia. Selcodebart is an investigational, first-in-class monoclonal antibody that blocks hemojuvelin, a co-receptor in the bone morphogenetic protein–signaling pathway that drives hepcidin expression.

RALLY-MF is a phase 2, open-label, multiple ascending–dose study assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of selcodebart in patients with myelofibrosis and anemia; the study plans to enroll approximately 90 patients, inclusive of 12 phase 1b patients dosed at 50 mg. Eligible adults had myelofibrosis with anemia—defined as a hemoglobin below 10 g/dL on at least 3 assessments over 84 days or 1 to 12 packed red blood cell units transfused in 84 days—and Dynamic International Prognostic Scoring System (DIPSS) Intermediate-1 to High disease; concomitant JAK inhibitor therapy was permitted.

Selcodebart was administered subcutaneously at 50 mg, with dose escalation to 75 mg on day 57 in patients with an insufficient response. As of the April 27, 2026, data cut, 61 patients were included in the analysis; at baseline, the median age was 71 years, 52.5% were receiving concomitant JAK inhibitors, 83.6% had DIPSS Intermediate-2 disease, and the median baseline hemoglobin was 8.4 g/dL. Selcodebart is not approved for use in any jurisdiction worldwide.

Reference

Gangat N, Tefferi A, Hexner E, et al. RALLY-MF: initial efficacy of a phase 2 study of DISC-0974, an anti-hemokuvelin antibody, to treat anemia in myelofibrosis. Presented at: 2026 Society of Hematologic Oncology (SOHO) Annual Meeting; September 9-12, 2026; Houston, TX. Abstract MPN-099.