Clinical Summary:

• Design/Population: The phase 2 RALLY-MF study evaluated DISC-0974, a hemojuvelin-blocking monoclonal antibody, in patients with primary or secondary myelofibrosis and anemia, including those receiving concomitant Janus kinase inhibitor therapy.
• Key Outcomes: DISC-0974 reduced hepcidin levels, mobilized iron, and produced meaningful hematologic responses across transfusion-dependent and non–transfusion-dependent cohorts. Improvements in fatigue were observed, and the treatment was well tolerated, with no serious or grade ≥ 3 adverse events considered treatment related.
• Clinical Relevance: These findings support hepcidin inhibition as a promising therapeutic strategy for treating anemia in myelofibrosis, including among patients receiving JAK inhibitor therapy.

Results from the ongoing, phase 2 RALLY-MF trial demonstrated that DISC-0974 produced meaningful hematologic responses and improved fatigue in patients with myelofibrosis-associated anemia, supporting hepcidin inhibition as a potential treatment strategy for this unmet clinical need.

These results were presented by Naseema Gangat, MBBS, Mayo Clinic Rochester, Rochester, Minnesota, at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this open-label phase 2 trial, 47 patients with primary or secondary myelofibrosis and anemia were enrolled to receive 50 mg of DISC-0974 subcutaneously every month for up to 6 doses, with dose escalation to 75 mg permitted for inadequate or lost response. Patients were enrolled into non–transfusion-dependent (n = 30), low transfusion burden (n = 10), or high transfusion burden (n = 7) cohorts based on red blood cell transfusion requirements. Fifty-three percent of patients were receiving concomitant JAK inhibitor therapy. 

The primary end point was major hematologic response, defined according to transfusion status. Secondary end points included pharmacokinetic and pharmacodynamic markers of iron regulation and safety.

At analysis, DISC-0974 produced sustained reductions in hepcidin levels and mobilized iron across all treatment cohorts. Among evaluable patients, 50% of non–transfusion-dependent patients achieved a mean hemoglobin increase of at least 1.5 g/dL that was maintained for at least 12 weeks. Transfusion independence for at least 16 weeks was achieved by 71% of patients with a low transfusion burden, while 67% of patients with a high transfusion burden achieved at least a 50% reduction in transfusion requirements.

Major hematologic response rates were similar regardless of concomitant JAK inhibitor therapy, with response rates of 50% among patients receiving and not receiving JAK inhibitors. DISC-0974 also produced meaningful improvements in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) scores among non–transfusion-dependent patients and those with a low transfusion burden. 

DISC-0974 was generally well tolerated. Serious adverse events (n = 9) and grade ≥ 3 adverse events (n = 16) were considered unrelated to treatment, and no patients discontinued therapy because of adverse events.

“These data validate hepcidin reduction as a promising approach to treating anemia in [myelofibrosis],” concluded Dr Gangat.

Source: 

Gangat N, Tefferi A, Bose P, et al. RALLY-MF: Initial efficacy of a phase 2 study of DISC-0974, an anti-hemojuvelin antibody, to treat anemia in myelofibrosis. Presented at the 2025 ASCO Annual Meeting; May 30–June 3, 2025; Chicago, Illinois. Abstract 6501.