Disc Medicine's DISC-0974 Shows Promising Results for Myelofibrosis Anemia in Phase 2 Trial
核心洞察
Disc Medicine reported positive initial data from the RALLY-MF Phase 2 trial of DISC-0974, demonstrating meaningful anemia (搜索) responses across all patient subgroups with myelofibrosis (搜索) regardless of baseline transfusion status.
The treatment achieved substantial reductions in hepcidin levels exceeding 75% from baseline and corresponding increases in serum iron, with 63% of non-transfusion dependent patients achieving hemoglobin increases of ≥1 g/dL for ≥12 weeks.
DISC-0974 showed efficacy independent of concomitant JAK inhibitor (搜索) therapy use, with 71% of low transfusion burden patients achieving transfusion independence over a 16-week period.
Disc Medicine presented encouraging initial data from its RALLY-MF Phase 2 trial of DISC-0974 for treating anemia (搜索) in myelofibrosis (搜索) patients at the ASH Annual Meeting in Orlando, Florida. The results demonstrated substantial reductions in hepcidin and increases in iron levels that translated to clinically meaningful improvements in anemia across a broad range of patient types.
The ongoing Phase 2 open-label study enrolled 47 adult patients with myelofibrosis (搜索) and anemia (搜索) as of the October 16 data cutoff, with 34 patients having sufficient follow-up for responder analysis. Patients were categorized into three groups: non-transfusion dependent receiving no transfusions (nTD, n=24), transfusion dependent with low transfusion burden (TD Low, n=7), and transfusion dependent with high transfusion burden (TD High, n=3). The trial included both patients receiving concomitant JAK inhibitor (搜索) therapy (n=18) and those not receiving JAK inhibitor therapy (n=16).
Treatment Protocol and Mechanism
DISC-0974 was administered subcutaneously at 50 mg every 4 weeks for up to 6 treatments. The drug targets iron homeostasis pathways, achieving consistent and substantial decreases in hepcidin reaching greater than 75% reduction from baseline with corresponding increases in serum iron levels.
Efficacy Results Across Patient Subgroups
The trial demonstrated robust hematologic responses across different patient populations. Among non-transfusion dependent patients, 63% achieved a hemoglobin increase of ≥1 g/dL for ≥12 weeks (overall response), while 50% had an increase of ≥1.5 g/dL for ≥12 weeks (major response).
For patients with low transfusion burden, 71% achieved transfusion independence over a 16-week period, representing a major response. Among high transfusion burden patients with at least 85 days on study, 67% achieved a ≥50% reduction in transfusion requirement. Initial data for an additional three high transfusion burden patients showed trends toward major response of transfusion independence lasting more than 12 weeks.
JAK Inhibitor Independence
A notable finding was that anemia (搜索) response occurred independent of concomitant JAK inhibitor (搜索) therapy use. Fifty percent of patients receiving concomitant JAK inhibitor therapy achieved a major hematologic response, demonstrating the drug's potential as both monotherapy and combination treatment.
"We are excited that we continue to see robust hematologic responses to DISC-0974 regardless of background JAK inhibitor (搜索) therapy," said John Quisel, J.D., Ph.D., President and Chief Executive Officer of Disc Medicine. "It is also encouraging to see these hematologic improvements translating into reduced transfusion burden and fatigue."
Quality of Life Improvements
Beyond hematologic parameters, dosing with DISC-0974 was associated with improvements in FACIT-Fatigue scores in both non-transfusion dependent and low transfusion burden participants, suggesting meaningful quality of life benefits.
Safety Profile
DISC-0974 was generally well-tolerated throughout the study period. Diarrhea and urinary tract infections, neither considered serious, were the only adverse events considered related to DISC-0974 and reported in two or more subjects. The majority of adverse events were not considered related to the study drug.
Addressing Unmet Medical Need
The results address a significant gap in myelofibrosis (搜索) treatment, as Quisel noted: "We look forward to advancing this program with the goal of addressing a significant unmet need as anemia (搜索) is one of the key manifestations of MF and there is currently no therapy approved to treat anemia in this population."
Future Development Plans
Disc Medicine plans to share additional data in the second half of 2026. The company also presented a poster outlining the trial design for an ongoing Phase 2 study of the anti-TMPRSS6 (搜索) antibody DISC-3405 in polycythemia vera (搜索) requiring frequent phlebotomy, expanding their hematologic disease portfolio.