Investigational drug that reduces hepcidin offers promise for treating anemia
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Key takeaways:
- Researchers report positive results from a phase 1b/2a placebo-controlled study of DISC-0974, an anti-hemojuvelin antibody.
- The investigational drug reduces hepcidin in patients with anemia.
LONG BEACH, Calif. — Researchers reported results from a phase 1b/2a placebo-controlled study of DISC-0974, an anti-hemojuvelin antibody to treat anemia in patients with chronic kidney disease.
“Hepcidin, a key regulator of iron homeostasis, is pathologically elevated in patients with non-dialysis dependent chronic kidney disease (NDD-CKD) and anemia,” Samir Arora, MD, chief growth officer at Centricity Research, and colleagues wrote in a poster presented at the National Kidney Foundation Spring Clinical Meetings. “Hepcidin elevations contribute to the onset, maintenance and severity of anemia.”
Disc-0974 (Disc Medicine) reduces hepcidin in patients with anemia, the researchers noted. “Hemojuvelin positive regulates hepatic hepcidin production through [bone morphogenetic protein] BMP/SMAD signaling,” Geoffrey Block, MD, from Rocky Mountain Kidney Care in Denver and co-author of the poster, told Healio. “Hepcidin is the key regulator of export of intracellular-stored iron by affecting ferroportin expression.
“DISC-0974 is a monoclonal [antibody] AB selectively targeting hemojuvelin, which then results in suppression of hepcidin levels, allowing mobilization of intracellular iron stores,” Block said.
In the double-blinded, placebo-controlled study, 32 adults with NDD-CKD at stages 2 to 5 and a hemoglobin of less than 10.5 g/dL in women or less than 11 g/dL in men, serum ferritin levels of 100 g/L or greater and TSAT of 30% or less were identified for the study. “Exclusion criteria include concomitant treatment with therapeutic oral or IV iron, erythropoietin stimulating agents [ESAs] or blood transfusions,” the authors of the poster wrote.
Participants received a single dose of DISC-0974 SC through 57 days of follow-up.
Primary endpoints included adverse events, clinical laboratory assessments, vital signs, physical exams and electrocardiograms.
“The results showed that DISC-0974 demonstrated dose-dependent reductions in serum hepcidin, increases in serum iron with doses up to 56 mg administered subcutaneously and increasing trends in reticulocyte hemoglobin, mean corpuscular hemoglobin, total Hgb and [red blood cell] RBC count,” the authors wrote.
“We believe that many patients with CKD and anemia are affected by elevated hepcidin levels,” Block told Healio. “By alleviating the hepcidin-induced sequestration of iron, DISC-0974 has the potential to be an alternative treatment for anemia in CKD without the risks associated with current therapies such as ESAs or IV iron.
“In the group of patients for whom hepcidin is the predominant factor driving anemia, ie, those with inflammation, it is possible that hemojuvelin could eliminate the need for ESAs,” Block said.
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Arora S, et al. Paper 446. Presented at: NKF Spring Clinical Meetings; May 14-18, 2024; Long Beach, Calif.
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