Background: Iron overload is a significant complication in patients with hereditary hemochromatosis and hereditary hemolytic anemia (esp. sickle cell disease and thalassemia). LJPC-401, a synthetically produced peptide identical to endogenous human hepcidin, is being developed as a therapeutic intervention for iron overload in these conditions.


Phase 1, randomized, double-blind, two-arm, placebo-controlled, single dose escalation, and multiple dose study to assess the safety, tolerability, and pharmacokinetics (PK) /pharmacodynamics (PD) of LJPC-401 in healthy adults. Eligible healthy adults were randomized in a 3:1 ratio to receive either LJPC-401 or placebo as a subcutaneous (SC) injection in single-dose cohorts (Arm A) or a multiple-dose cohort (Arm B, twice weekly for two weeks). Subjects were assigned to receive LJPC-401 at doses of 4, 10, or 20 mg.

Serial blood samples were collected up to one-week post dose in the single-dose cohort and up to two weeks in the multiple-dose cohort for PK and PD assessments. PD assessments included effects on serum iron, ferritin, unsaturated iron binding capacity (UIBC), and transferrin saturation (TSAT).


Twenty-one healthy adults were randomized and included in analyses (12 from Arm A and 9 from Arm B).

In Arm A, dose-related increases in mean baseline-corrected LJPC-401 concentrations were observed following single SC doses of 4, 10, and 20 mg LJPC-401. Peak concentrations were observed at approximately 2 hours postdose for all doses. LJPC-401 concentrations returned to near baseline by approximately 1 day postdose for the 4- and 10-mg dose groups and by 7 days postdose for all groups. In Arm A, dose-dependent decreases in serum iron were observed in all LJPC-401 dose groups, beginning at 2 hours postdose. The largest percent decrease in serum iron for the LJPC-401 groups occurred at the 12-hour postdose timepoint and was a mean (SD) of−56.0% (16.9%) in the 4-mg group, −66.9% (6.1%) in the 10-mg group, and −79.7% (4.1%) in the 20-mg group. Serum iron levels returned to baseline within approximately 24 hours in the 4-mg dose group and within approximately 48 hours after dosing in the 10 and 20 mg dose groups.

In Arm B (10 mg dose twice weekly), decreases in mean serum iron from baseline were observed after each dose of LJPC-401. The largest percent decreases in serum iron for the LJPC-401 group was observed at Hours 8 and 12 for the Day 1 dose (mean (SD): −69.1% [9.6%] and −69.2% [17.8%], respectively) and at Hour 12 for the Day 11 dose (−73.0% [13.1%]).

Dose-related increases in UIBC were observed, along with dose-related decreases in TSAT, which were similar to those observed for serum iron. Dose-related prolonged increases in serum ferritin were observed. Diurnal variation patterns were seen in endogenous hepcidin and baseline iron levels in placebo subjects.

No treatment-emergent serious adverse events were reported. One subject discontinued treatment due to a TEAE (exacerbation of pre-existing atopic dermatitis) two days after initial 10 mg dose. No trends were observed in clinical laboratory data, vital signs, ECGs, or concomitant medications. No subjects tested positive for antibodies specific to LJPC-401.


LJPC-401 was well tolerated at single doses between 4 and 20 mg (the highest dose tested), and at doses of 10 mg twice weekly in healthy adults, and resulted in decreases in serum iron levels compared with baseline. Serum ferritin increased over the time course of observations, consistent with an increased distribution of iron into the macrophage compartment, secondary to decreased iron egress into the plasma transferrin compartment. These results warrant further research in longer-term studies.


Porter:Agios: Honoraria; Novartis: Consultancy; Cerus: Honoraria. Taher:Celgene Corp.: Research Funding; Protagonist Therapeutics: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; La Jolla Pharmaceutical: Research Funding; Ionis Pharmaceuticals: Consultancy. Shen:La Jolla Pharmaceutical Company: Employment, Equity Ownership. Chen:La Jolla Pharmaceutical Company: Employment, Equity Ownership. Chawla:La Jolla Pharmaceutical Company: Employment, Equity Ownership. Tidmarsh:La Jolla Pharmaceutical Company: Employment, Equity Ownership.

Author notes


Asterisk with author names denotes non-ASH members.

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