Kidney Week

Abstract: FR-PO1162

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: Kidney Function and Extrarenal Complications
  October 25, 2024 | 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

• Arora, Samir, Centricity Research, Columbus, Ohio, United States

Samir Arora, MD

• Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States

Pablo E. Pergola, MD, PhD

• Silva, Arnold L., Boise Kidney & Hypertension Institute, Meridian, Indiana, United States

Arnold L. Silva, MD, PhD

• Block, Geoffrey A., Rocky Mountain Kidney Care, Lone Tree, Colorado, United States

Geoffrey A. Block, MD, FASN

• Bhatt, Sima, Disc Medicine Inc, Watertown, Massachusetts, United States

Sima Bhatt, MD

• Buch, Akshay, Disc Medicine Inc, Watertown, Massachusetts, United States

Akshay Buch, PhD

• Pelletier, Olivia, Disc Medicine Inc, Watertown, Massachusetts, United States

Olivia Pelletier, MBA

• Savage, Will, Disc Medicine Inc, Watertown, Massachusetts, United States

Will Savage, MD, PhD

Background

Hepcidin, a key regulator of iron homeostasis, is pathologically elevated in patients with non-dialysis-dependent CKD (NDD-CKD) and contributes to the onset and severity of anemia. DISC-0974 is an investigational, first-in-class, monoclonal antibody that blocks hemojuvelin (HJV), a co-receptor in the BMP-signaling pathway regulating hepcidin expression. By inhibiting endogenous production of hepcidin and enhancing iron availability, DISC-0974 may provide a novel approach for treatment of anemia.

Methods

DISC-0974-103 is a Phase 1b, double-blind, placebo-controlled, single-ascending dose study (NCT05745883) to assess the safety, PK, and PD of DISC-0974 in patients with NDD-CKD and anemia. On Day 1, participants receive a single dose of DISC-0974 subcutaneously with evaluations through 57 days of follow-up. Dose-escalation is planned across 4 cohorts (n=8), with 3:1 randomization of DISC-0974 (28, 40, 60, and 90 mg) to placebo. Eligible participants include NDD-CKD Stages 2-5, hemoglobin <11 g/dL, serum ferritin ≥75 μg/L, and transferrin saturation (TSAT) ≤35%. Major exclusionary criteria include concomitant treatment with intravenous iron or ESAs.

Results

Initial data in participants (n=8) who received a single dose of 28 mg DISC-0974 showed sustained reductions in serum hepcidin (Figure 1a) with a corresponding doubling of TSAT (Figure 1b) over mean baseline TSAT values of 17%. DISC-0974 was generally well tolerated; 2 subjects treated with DISC-0974 had a TEAE (33%) vs. 2 on placebo (100%); 2 treated subjects had SAEs deemed not related to DISC-0974.

Conclusion

Initial data provide proof-of-concept that DISC-0974 can result in meaningful reductions in hepcidin and improve mobilization of iron. DISC-0974 was generally well tolerated at the evaluated dose level. Additional ascending-dose cohort data will be presented.

a) Serum hepcidin levels and b) change in TSAT over time following single-dose administration of 28 mg DISC-0974 (n=6) or placebo (n=2)