Abstract: SA-PO1183
A Phase 1b, Double-Blind, Placebo-Controlled Study of DISC-0974, an Anti-Hemojuvelin Antibody, in Patients with Nondialysis-Dependent CKD and Anemia
Session Information
- CKD: Biomarkers and Emerging Tools for Diagnosis and Monitoring
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States
- Newby, F. David, Nephrology and Hypertension Specialists, P.C., Dalton, Georgia, United States
- Zakaryan, Vahagn A., Columbus Nephrology, Inc., Columbus, Ohio, United States
- Silva, Arnold L., Boise Kidney & Hypertension Institute, Meridian, Idaho, United States
- Gonzalez, Alfonso, Flourish Research, Winter Park, Florida, United States
- Fernandez, John, Total Research Group, Miami, Florida, United States
- Block, Geoff, US Renal Care, Lone Tree, Colorado, United States
- Bhatt, Sima, Disc Medicine Inc, Watertown, Massachusetts, United States
- Buch, Akshay, Disc Medicine Inc, Watertown, Massachusetts, United States
- Pelletier, Olivia, Disc Medicine Inc, Watertown, Massachusetts, United States
- Savage, Will, Disc Medicine Inc, Watertown, Massachusetts, United States
Background
Hepcidin is pathologically elevated in patients with NDD-CKD and anemia. DISC-0974, an investigational, monoclonal antibody directed against hemojuvelin, suppresses hepcidin. In healthy volunteers, treatment with DISC-0974 showed dose-dependent reductions in serum hepcidin, increases in serum iron, increasing trends in hemoglobin (Hgb), and a favorable safety profile. DISC-0974-103 is a Phase 1b, double-blind, placebo-controlled study (NCT05745883) to assess safety, PK, PD, and efficacy of single (dose-escalation) and multiple doses of DISC-0974 SC in participants with NDD-CKD and anemia.
Methods
The single-ascending dose (SAD) portion consisted of 4 cohorts (n=8-12) randomized 3:1 to DISC-0974 (28, 40, 60, 90 mg) or placebo with evaluations through Day 57. The multiple-dose portion of the study includes 2 cohorts randomized 2:1 to DISC-0974 (60 or 90 mg) or placebo administered every 4 weeks for 3 doses. Participants are CKD Stages 2-5, Hgb <11 g/dL, serum ferritin ≥50 μg/L, and TSAT ≤35%. Exclusionary criteria: concomitant treatment with IV iron or ESAs.
Results
At data cut, 21 participants had enrolled at 3 dose levels for the SAD portion: 28 mg (n=9), 40 mg (n=6), 60 mg (n=6). DISC-0974 led to sustained reductions in serum hepcidin, median reduction >75% from baseline at 60 mg, with sustained increase in TSAT vs placebo across dose levels. An early sustained increase in mean reticulocyte Hgb across all dose groups was noted through Day 22. Most AEs were not related to DISC-0974, and treatment-related AEs were Grade 1/2. DISC-0974 has acceptable safety and tolerability at the dose levels evaluated.
Conclusion
DISC-0974 resulted in decreased hepcidin and increased serum TSAT, along with increased mean reticulocyte Hgb compared to placebo. These data provide initial proof that in CKD, hemojuvelin-targeting therapy with DISC-0974 can suppress hepcidin, mobilize iron into circulation, and improve hematologic parameters. Multiple-dose cohort enrollment is ongoing to evaluate optimal regimen for sustained Hgb increase. Complete SAD and available multiple-dose cohort data are forthcoming.
Funding
- Commercial Support – Disc Medicine