AN OPEN-LABEL PHASE 2, DOSE-FINDING STUDY OF THE SAFETY AND EFFICACY OF RUSFERTIDE (PTG-300), A HEPCIDIN MIMETIC, IN PATIENTS WITH HEREDITARY HEMOCHROMATOSIS

Background: Rusfertide, a peptide mimetic of hepcidin, a key regulator of iron distribution and utilization, demonstrated control of iron in an animal model of hereditary hemochromatosis (HH). We conducted an efficacy study in HH patients to expand on these nonclinical findings.

Methods: This single-arm, open-label, dose-finding Phase 2 study investigated subcutaneous rusfertide in HH patients on a stable phlebotomy frequency of 0.25–1 phlebotomies/month for at least 6 months. Patients with clinically meaningful laboratory abnormalities and those receiving iron chelation therapy or erythrocytapheresis were excluded. Patients received individually titrated rusfertide doses once or twice a week to maintain transferrin saturation (TSAT) below 45% and were followed for 6 mo. Study measures included TSAT, serum iron, transferrin and ferritin, liver iron content (LIC) measured by FerriScan MRI, adverse events (AEs), and patient-reported outcomes on the Patient Global Impression of Change (PGI-C) and Medical Outcomes Study Questionnaire Short Form Health Survey (SF‑36).

Results: Sixteen patients (10 male/6 female) were enrolled. Mean age and weight were 62.5 years and 88.1 kg, respectively. Average prestudy phlebotomy rate was 0.27 phlebotomies/month compared to 0.03 phlebotomies/month during study (p<0.0001; Figure A). Baseline TSAT was 45.0% compared to an average of 30.4% during study (p=0.0025; B). Serum iron were reduced from 24.5 µmol/L prestudy to an average of 17.7 µmol/L during the study (p=0.0059). LIC values were maintained at prestudy levels (C). There was no significant difference in average serum ferritin post-treatment relative to baseline (82.3 µg/L versus 85.0 µg/L). Average serum transferrin post-treatment was similar to baseline (2.32 g/L versus 2.45 g/L). Improvements were noted in SF-36 Role Physical and Role Emotional subcomponents. All treatment-related AEs were characterized as CTCAE grade 1 or 2.

Conclusion: Rusfertide demonstrated a pharmacologic effect in reducing TSAT and serum iron. These pharmacodynamic effects corresponded with a reduced need for phlebotomy during the study, control in LIC and improvements in patient reported outcomes. These data indicate rusfertide was well tolerated in patients with HH and controls LIC in the absence of phlebotomy, supporting development of rusfertide as a treatment for HH.