Investigational treatment reduces hepcidin, potentially beneficial to patients with anemia
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Key takeaways:
- Single dose of DISC-0974 shows positive safety and tolerability profiles among healthy patients.
- This dose also elevates iron in a healthy population.
AUSTIN, Texas —An investigational treatment, DISC-0974, can reduce hepcidin and elevate iron levels in healthy patients, according to a presenter at the National Kidney Foundation Spring Clinical Meetings.
This may lead to therapeutic benefits for patients with chronic kidney disease and anemia.
“DISC-0974 is an investigational first-in-class monoclonal antibody-targeting hemojuvelin (HJV) to suppress the production of hepcidin and make iron available for red blood cell production. Pathologic elevations in hepcidin, a central regulator of iron homeostasis, contributes to anemia in CKD, making it a good potential target for DISC-0974,” William Savage, MD, PhD, the chief medical officer of Disc Medicine, told Healio. “There remains a need for new treatment approaches to manage anemia in CKD, particularly for the non-dialysis dependent population, many of whom currently go untreated. IV iron and [erythropoiesis-stimulating agents] ESAs do not address the underlying problem of functional iron deficiency caused by chronic hepcidin elevation.”
In a phase 1a, double-blind, placebo-controlled and single-ascending dose study, researchers examined the effect of DISC-0974, a monoclonal antibody developed to attack HJV. According to the poster, targeting HJV can reduce hepcidin and increase serum iron, which may benefit patients with anemia and chronic kidney disease.
Investigators enrolled 42 volunteers and randomized them 3:1 to receive either the intervention or placebo. Participants were treated with 7 mg, 14 mg, 28 mg and 56 mg (subcutaneous or IV) of DISC-0974. Researchers considered safety and tolerability the primary outcomes, with pharmacokinetics and pharmacodynamics as the secondary outcomes.
Overall, a single dose of DISC-0974 in healthy participants met acceptable safety and tolerability benchmarks, although two patients experienced adverse events that researchers said were possibly related to the study drug. Further, DISC-0974 dosing reduced hepcidin and increased transferrin serum iron saturation.
Researchers observed a “robust iron response” among participants in the 56-mg subcutaneous group. Iron levels remained elevated for 3 weeks. Moreover, average hemoglobin levels and red blood cell counts were higher in this group than the placebo group.
Future research will be conducted in the phase 1b study, which will involve patients with non-dialysis dependent CKD and anemia. According to Savage, “Subjects with iron-deficiency anemia will be excluded by ferritin and [transferrin serum iron saturation] TSAT levels.” Additionally, he said, researchers will measure safety, pharmacokinetics, hepcidin and iron levels after each dose cohort (n=8) before proceeding to the next dose.
“The phase 1 healthy volunteer study demonstrates that a single dose of DISC-0974 in healthy volunteers has a favorable safety/tolerability profile and results in hepcidin suppression and iron elevation. There is also evidence of augmented hemoglobinization in a healthy population that is not iron deficient,” Savage said. “These observations may translate into a therapeutic effect for patients with CKD and anemia, a population with high unmet need and a scientific rationale for the DISC-0974’s mechanism. DISC-0974 is a potential first-in-class therapeutic candidate that works through a fundamentally different pathway from the ESAs. If effective, it could provide a novel approach to the treatment of CKD anemia.”
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Novikov N. et al. Poster 184. Presented at: National Kidney Foundation Spring Clinical Meetings; April 11-15, 2023; Austin, Texas.
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