Disc Medicine, Inc. (NASDAQ:IRON) has announced positive data from its Phase 1b trial of DISC-0974 in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and anemia. The data, presented at the 2024 American Society of Nephrology (ASN) Kidney Week, highlight the potential of DISC-0974 to address anemia by targeting hepcidin, a key regulator of iron homeostasis.
The Phase 1b study included single ascending dose (SAD) cohorts, with patients receiving a single dose of placebo or DISC-0974 at 28 mg, 40 mg, or 60 mg. The results demonstrated a substantial, durable, and dose-dependent reduction in hepcidin from baseline compared to placebo. Notably, the median reduction in hepcidin exceeded 75% from baseline at the highest dose level.
Impact on Iron Mobilization and Erythropoiesis
In addition to hepcidin reduction, DISC-0974 led to a meaningful and sustained increase in transferrin saturation from baseline compared to placebo across all dose levels, with a median increase of up to 3-fold from baseline at the highest dose level. The treatment also resulted in an early and sustained increase in mean reticulocyte hemoglobin from baseline across all dose groups through Day 22 and beyond. Maximal mean values through Day 22 were +1.14 pg at 28 mg, +1.49 pg at 40 mg, and +1.53 pg at 60 mg, compared with +0.21 pg on placebo.
Hemoglobin Level Improvements
The study also showed an increase in mean hemoglobin from baseline across dose groups over the study period. The change was greater than placebo: +0.35 g/dL at 28 mg, +0.54 g/dL at 40 mg, and +0.55 g/dL at 60 mg. The mean maximal increase in hemoglobin was +0.8 g/dL at 40 mg and +0.7 g/dL at 60 mg compared with +0.2 g/dL on placebo. The maximal observed individual increase in hemoglobin was up to +0.95 g/dL at 28 mg, +1.5 g/dL at 40 mg, and +1.8 g/dL at 60 mg.
Safety and Tolerability
DISC-0974 demonstrated acceptable safety and tolerability at all evaluated dose levels. The majority of adverse events were deemed not related to DISC-0974, and all adverse events assessed as treatment-related were Grade 1 or 2.
Anemia in Chronic Kidney Disease: A Significant Unmet Need
Anemia is a common and serious complication of chronic kidney disease (CKD), affecting approximately 5 to 6 million patients in the U.S. alone. Elevated hepcidin is a primary cause of anemia in CKD patients, preventing erythropoiesis by depriving developing red blood cells of iron. Current treatments have limitations, and many CKD patients do not receive any treatment for their anemia due to the complexity of outpatient administration and potential safety concerns.
Company Comments
"We are pleased to present these updated results, which provide the first clinical evidence in CKD anemia that reducing hepcidin through hemojuvelin translates into increased erythropoiesis and hemoglobin," said John Quisel, JD, PhD, President and Chief Executive Officer of Disc Medicine. "Importantly, we were able to observe activity following only a single dose of DISC-0974, which will enable us to efficiently explore dose regimens in the multiple-dose portion of the Phase 1b study."
Quisel added, "We have now shown that DISC-0974 can improve anemia in the settings of both myelofibrosis and chronic kidney disease. This speaks to the much broader potential for DISC-0974 to address anemia caused by a range of inflammatory and chronic diseases, each of which are associated with elevated hepcidin, and we look forward to providing our plans to access these indications."
