Disc Medicine (NASDAQ:IRON) has announced positive updated results from its Phase 1b trial of DISC-0974 in patients with myelofibrosis (MF) and anemia. The data, presented at the 2024 American Society of Hematology (ASH) annual meeting, highlight the potential of DISC-0974 to address anemia in MF patients, regardless of transfusion status or concomitant JAK inhibitor therapy. The company has initiated a Phase 2 study following these results.
The Phase 1b multi-center, open-label study enrolled 35 adult patients with MF and anemia. The patients were categorized into non-transfusion dependent (nTD, n=23), transfusion dependent with low transfusion burden (TD Low, n=5), and transfusion dependent with high transfusion burden (TD High, n=7). The trial included patients receiving concomitant JAK inhibitor therapy (n=13) and those not receiving JAK inhibitor therapy (n=22). DISC-0974 was administered subcutaneously every 4 weeks for up to 6 treatments at doses ranging from 14 mg to 100 mg.
Key Findings from the Phase 1b Trial
The study demonstrated consistent and substantial decreases in hepcidin, reaching >75% reduction from baseline, and corresponding increases in serum iron across patients. These changes translated to increased levels of reticulocyte hemoglobin and hemoglobin. Specifically:
- 68% of baseline nTD patients achieved a hemoglobin increase of ≥1.5 g/dL during the study period, with 50% having sustained increases for ≥12 weeks.
- 100% of TD Low patients achieved a ≥50% reduction in transfusion requirement, with 80% achieving transfusion independence (TI) over a 16-week period.
- 60% of TD High patients achieved a ≥50% reduction in transfusion requirement, with 40% achieving transfusion independence over a 12-week period.
- 54% of patients receiving concomitant JAK inhibitor therapy achieved a major hematologic response.
Safety and Tolerability
DISC-0974 was generally well-tolerated at all evaluated dose levels. Diarrhea was the only adverse event (AE) considered related to DISC-0974 and reported in two or more subjects. The majority of AEs were not considered related to DISC-0974.
Mechanism of Action and Clinical Significance
DISC-0974 is an investigational monoclonal antibody (mAb) targeting hemojuvelin (HJV), a BMP-signaling co-receptor. It is designed to suppress hepcidin production and increase serum iron levels in patients suffering from anemia of inflammation. Anemia of inflammation, driven by elevated hepcidin, is the second most common form of anemia, affecting millions in the US across various diseases, including chronic kidney disease and myelofibrosis.
Myelofibrosis and Anemia
Myelofibrosis is a rare, chronic blood cancer affecting an estimated 25,000 patients in the United States. Anemia is a primary clinical manifestation, with over 80% of MF patients experiencing it at diagnosis. Hepcidin is elevated approximately 12-fold in MF patients and correlates with disease severity, anemia, and the need for red blood cell transfusions.
Management Commentary
"With the presentation of this expanded data set from our phase 1b study, we are encouraged by the continued demonstration of robust hematologic activity of DISC-0974, including durable hemoglobin increases in all patient subgroups and meaningful reductions in transfusion burden. Importantly, we observed strong responses regardless of patients’ baseline transfusion burden or concomitant use of JAK inhibitors," said John Quisel, JD, PhD, President and Chief Executive Officer of Disc Medicine. "With this data in hand, I’m pleased to announce that we have now started a phase 2 trial in myelofibrosis patients with anemia."
