Selcodebart Shows Hematologic Activity in Myelofibrosis-Associated Anemia

As reported on ONC Live, early findings from the phase 1/2 RALLY-MF trial suggest selcodebart may improve hemoglobin levels and reduce dependence on red blood cell transfusions in patients with myelofibrosis-associated anemia, including those receiving JAK inhibitor therapy.

Selcodebart (DISC-0974), an investigational antibody targeting hemojuvelin, demonstrated hematologic activity across multiple groups of patients with anemia associated with myelofibrosis in the phase 1/2 RALLY-MF trial (NCT05320198). Initial efficacy findings were presented at the 2026 SOHO Annual Meeting.

As of the April 27, 2026, data cutoff, 50 patients were evaluable for efficacy. Among 31 patients who were not dependent on transfusions, 55% experienced an average hemoglobin increase of at least 1.5 g/dL that persisted for 12 weeks or more.

Transfusion-dependent patients also experienced responses. Seven of 11 evaluable patients (64%) with a low baseline transfusion requirement became transfusion independent for at least 16 weeks. Among 8 evaluable patients with a higher transfusion requirement, 4 (50%) achieved transfusion independence lasting at least 12 weeks.

Importantly, hematologic responses did not appear to depend on concomitant JAK inhibitor treatment. Major responses were reported in 56% of evaluable patients receiving a JAK inhibitor and 56% of those who were not.

RALLY-MF Investigates a Different Approach to Anemia

Anemia is a significant complication of myelofibrosis, and elevated hepcidin has been implicated in its development and severity. Higher hepcidin levels can interfere with the availability of iron needed for red blood cell production.

Selcodebart is designed to address this pathway by inhibiting hemojuvelin, which participates in signaling involved in hepatic hepcidin production. Reducing hepcidin is intended to make stored iron more readily available, enhance iron absorption, and ultimately support hemoglobin production.

RALLY-MF enrolled adults with primary myelofibrosis, post–essential thrombocythemia myelofibrosis, or post–polycythemia vera myelofibrosis who had anemia that could not be explained by reversible factors such as bleeding, infection, iron deficiency, or vitamin B12 deficiency.

Participants were categorized according to their transfusion needs at baseline:

Non–transfusion dependent: hemoglobin below 10 g/dL with no transfusions required.
Low transfusion dependence: 1 to 2 units of packed red blood cells during an 84-day period.
High transfusion dependence: 3 to 12 units during an 84-day period.

Patients received subcutaneous selcodebart at 50 mg every 28 days for 6 treatment cycles. Those with an inadequate response could have their dose increased to 75 mg beginning on day 57. Continued treatment was optional after the initial study period, and patients receiving stable JAK inhibitor or hydroxyurea therapy were allowed to remain on those treatments.

By the cutoff, 61 patients had received selcodebart, including 35 who were non–transfusion dependent, 13 with low transfusion dependence, and 13 with high transfusion dependence.

Responses Were Observed Across Baseline Transfusion Groups

The investigators reported both relatively early responses and sustained benefit among some participants.

In the non–transfusion-dependent group, 17 responders had an average time to major hematologic response of 27 days, with substantial variability between patients. Among 14 participants evaluated for response duration, the longest major response averaged 318 days through the optional continuation period.

Among patients with low transfusion dependence, the average time to response was 4 days in 7 responders. Six patients included in the response-duration analysis had an average longest response of 345 days.

Responses were also observed in heavily transfusion-dependent patients. Four responders in that group had an average time to major response of 2 days. For 2 patients with available duration data, the longest response averaged 239 days.

Changes in hepcidin, iron availability, and hematologic outcomes were reported to be similar irrespective of concomitant JAK inhibition, including treatment with ruxolitinib, momelotinib, or pacritinib.

Hemoglobin Gains Associated With Improvements in Fatigue

The trial also assessed whether improvements in anemia translated into benefits patients could perceive in their daily lives.

Participants in the non–transfusion-dependent and low-transfusion-dependence groups achieved improvements on the FACIT-Fatigue scale that exceeded the established 3-point threshold for a clinically meaningful change.

The magnitude of hemoglobin improvement was significantly associated with changes in FACIT-Fatigue scores at the end of the study (P = .012). Hemoglobin changes were also significantly associated with improvement on the Patient Global Impression of Severity measure (P = .0004).

In addition, among patients with major hematologic responses in the non–transfusion-dependent and low-transfusion-dependence groups, half experienced at least a 50% reduction in total symptom scores on the Myeloproliferative Neoplasm Symptom Assessment Form by the end of the study.

Safety Findings From RALLY-MF

Treatment-emergent adverse events were reported in 56 of the 61 treated patients (91.8%), although investigators classified treatment-related events in 24.6% of patients.

Serious adverse events occurred in 19.7%, while 41.0% experienced an event of grade 3 or greater severity. Two patients (3.3%) experienced adverse events of special interest involving reduced renal function.

The most frequently reported treatment-emergent events were:

Muscle spasms: 21.3%
Diarrhea: 16.4%
Fatigue: 16.4%
Anemia: 14.8%
Headache: 14.8%
Dizziness: 13.1%
Urinary tract infection: 13.1%
Falls: 13.1%

One patient stopped treatment following nephrolithiasis, chronic kidney disease, and Clostridium colitis. Investigators did not consider these events related to selcodebart.

Early Findings Require Further Follow-Up

The initial RALLY-MF findings suggest that targeting the hepcidin pathway with selcodebart could improve hemoglobin levels or decrease transfusion requirements across different degrees of myelofibrosis-associated anemia. The comparable response rates among patients receiving and not receiving JAK inhibitors may also be relevant given the frequent use of these drugs in myelofibrosis.

However, the findings remain preliminary. RALLY-MF is a single-arm phase 1/2 trial without a randomized comparator, and the efficacy analyses included relatively small numbers of patients, particularly in the transfusion-dependent cohorts. Follow-up of non–transfusion-dependent participants and enrollment of transfusion-dependent patients were ongoing at the reported cutoff.

Key Takeaways

Selcodebart produced hematologic responses in patients with myelofibrosis-associated anemia across 3 levels of baseline transfusion burden.
55% of evaluable non–transfusion-dependent patients achieved the prespecified sustained hemoglobin improvement.
64% of evaluable patients with low transfusion dependence and 50% with high transfusion dependence achieved the respective transfusion-independence outcomes.
Major hematologic response rates were 56% both with and without concomitant JAK inhibitor treatment.
Improvements in hemoglobin were associated with improvements in patient-reported fatigue and overall disease severity.
Only 1 of 61 treated patients discontinued because of adverse events, which investigators considered unrelated to selcodebart.
The single-arm design and small efficacy populations mean that larger, controlled studies will be needed to establish the magnitude and durability of benefit.