Anti-Hemojuvelin Agent Counters Anemia in Myelofibrosis

In patients with myelofibrosis, an investigational, first-in-class, anti-hemojuvelin monoclonal antibody agent reduced anemia with acceptable safety. The results from a phase Ib/IIa study were presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.

“Anemia responses were achieved in [non-transfusion-dependent] and [transfusion-dependent] participants, regardless of concomitant [Janus kinase (JAK)] inhibitor use,” wrote lead investigator Naseema Gangat, MD, of Mayo Clinic in Rochester, Minnesota.

The agent in this open-label, multiple-ascending dose study, DISC-0974, was given to 11 adult patients with intermediate-2 or high-risk myelofibrosis and anemia. They received the agent subcutaneously once monthly in six doses. Use of concomitant hydroxyurea or a JAK inhibitor was permitted among the patients.

The investigators observed in all patients that DISC-0974 produced sustained, dose-dependent reductions in hepcidin and dose-dependent increases in serum iron.

Regarding changes in hemoglobin level, among the seven evaluable non-transfusion-dependent patients, 57% of those treated at the 28 mg and 50 mg dose levels of DISC-0974 saw an increase of 1.5 g/dL or greater from baseline. One of the two transfusion-dependent patients in the study achieved transfusion independence as defined by Gale criteria. Hematologic activity occurred in patients regardless of JAK inhibitor use.

“Sustained and substantial hepcidin reduction with DISC-0974 leads to increased serum iron that precedes anemia responses,” Dr. Gangat elaborated about the results.

Adverse events (AEs) of anemia, diarrhea, fatigue, and nausea were reported by at least two patients each. Three patients experienced grade 3 anemia, one patient experienced grade 3 headache, and one patient had serious worsening hip pain, though none of those AEs was attributed to DISC-0974.

Reference

Gangat N, Foran J, Halpern A, et al. A phase 1b trial of DISC-0974, an anti-hemojuvelin antibody, in participants with myelofibrosis and anemia. Abstract #MPN-153. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.