DISC-0974 shows durable anemia responses in myelofibrosis

Treatment with DISC-0974, Disc Medicine’s experimental antibody therapy for myelofibrosis-associated anemia, led to durable anemia responses across patient subgroups and clinically significant fatigue improvements in certain groups of people with myelofibrosis, according to updated Phase 2 trial data.

The Phase 1b/2 clinical trial, called RALLY-MF (NCT05320198), is testing DISC-0974 in adults ages 18 and older with myelofibrosis and anemia. Compared with the earlier dose-escalation Phase 1b portion, the ongoing Phase 2 expansion study includes a broader range of patients, including those with less advanced myelofibrosis and varying degrees of anemia and blood transfusion needs.

According to the company, anemia responses with DISC-0974 were observed regardless of participants’ transfusion needs at the start of the study and whether they were using JAK inhibitors, a class of therapies commonly used to treat myelofibrosis. The findings were presented at the American Society of Clinical Oncology (ASCO) annual meeting, held May 29–June 2 in Chicago.

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“We are excited to have solidified and strengthened the magnitude, durability, and consistency of responses as we have enrolled more patients and extended follow-up,” John Quisel, PhD, president and CEO of Disc, said in a company press release.

Disc said additional data from RALLY-MF are expected later this year. The company also expects to meet with the U.S. Food and Drug Administration (FDA) before the end of 2026 to discuss the therapy’s future development.

Myelofibrosis is a rare blood cancer in which scar tissue gradually builds up in the bone marrow, impairing the body’s ability to produce healthy blood cells and driving symptoms. Many people develop anemia, or low red blood cell levels, which can cause severe fatigue, weakness, shortness of breath, and an increased need for blood transfusions.

DISC-0974 is an experimental antibody therapy designed to block hemojuvelin, a protein involved in the production of hepcidin, a hormone that regulates iron levels in the body. Hepcidin levels are often abnormally high in people with myelofibrosis, limiting the availability of iron needed to make red blood cells. By lowering hepcidin levels, DISC-0974 is intended to increase iron availability and improve red blood cell production.

In the Phase 1b portion of RALLY-MF, 34 adults with more advanced myelofibrosis and anemia, including those who were and were not dependent on blood transfusions, received six monthly under-the-skin injections of DISC-0974 at doses ranging from 14 mg to 100 mg. Participants could continue receiving standard treatments for myelofibrosis, including JAK inhibitors, provided their doses remained stable.

The study’s main goal was to evaluate safety. Overall, DISC-0974 was generally well tolerated, with diarrhea being the only side effect considered at least possibly related to treatment that was reported in two or more participants. Most serious or severe adverse events were not considered related to the therapy.

Hepcidin reductions seen across patient groups

In the initial Phase 1b portion of the study, DISC-0974 reduced hepcidin levels by more than 80% on average, consistent with improved iron availability for red blood cell production. Corresponding anemia responses were observed across both transfusion-dependent and non-transfusion-dependent participants, as well as in those receiving JAK inhibitors.

At the time of the updated Phase 2 analysis, that portion of the study had enrolled 61 participants, of whom 50 were evaluable for efficacy. These included 31 patients who were not dependent on transfusions, 11 with lower transfusion needs, and eight who required more frequent transfusions. DISC-0974 was administered as a 50 mg under-the-skin injection every four weeks for up to six treatments.

Treatment led to sustained reductions in hepcidin levels of more than 75% from the initial level at the study’s start, accompanied by increases in blood iron levels. These changes translated into anemia responses across patient groups regardless of their transfusion needs at the start of the study.

Among participants who were not dependent on transfusions, 55% achieved clinically meaningful increases in hemoglobin levels of at least 1.5 grams per deciliter (g/dL) that were maintained for at least 12 weeks. Looking at a broader threshold, 68% of these participants achieved an overall response of at least a 1.0 g/dL increase for the same duration.

Among those who required transfusions, 64% of patients with lower transfusion needs became transfusion independent over 16 weeks, and 50% of those with higher transfusion needs became transfusion independent over 12 weeks. When patients who reduced their transfusion needs by at least half were included, the overall response rates rose to 73% and 88%, respectively.

Responses seen with JAK inhibitors

Among participants receiving JAK inhibitors, 56% achieved a major hematologic response and 72% an overall response, regardless of the specific therapy used.

DISC-0974 was also associated with clinically significant improvements in patient-reported fatigue among participants who were not dependent on transfusions and those with lower transfusion needs, with improvements correlated with hemoglobin increases. The therapy remained generally well tolerated, with diarrhea as the only treatment-related side effect reported by two or more participants.

“The activity observed both with and without background JAK inhibitor therapy, together with improvements in transfusion burden and fatigue, continues to support the potential for DISC-0974 to serve a broad population of patients living with [myelofibrosis]-associated anemia, an area where substantial unmet need remains,” Quisel said.