rusfertide (PTG-300)

P2, N=70, Completed, Protagonist Therapeutics, Inc. | Active, not recruiting --> Completed

P3, N=293, Active, not recruiting, Protagonist Therapeutics, Inc. | Trial completion date: Jun 2025 --> Jun 2027

P3, N=46, Active, not recruiting, Protagonist Therapeutics, Inc. | Enrolling by invitation --> Active, not recruiting

The treatment landscape of polycythemia vera (PV) has seen major advancements within the last decade including approval of ruxolitinib in the second line setting after hydroxyurea, ropegylated interferon-α2b, and advanced clinical development of a novel class of agents called hepcidin mimetics...The discovery of hepcidin mimetics has come as a breakthrough in restoring iron homeostasis, achieving phlebotomy-independence and may lead to improved thrombosis-free survival with stricter hematocrit control. On the other hand, emerging data with IFN- α and ruxolitinib as well as combination of the two agents suggests the potential for achieving molecular remission in a subset of PV patients and long-term follow-up is awaited to validate the correlation of molecular responses with clinically relevant outcomes of progression-free and thrombosis-free survival.

P3, N=250, Active, not recruiting, Protagonist Therapeutics, Inc. | Recruiting --> Active, not recruiting

P3, N=250, Recruiting, Protagonist Therapeutics, Inc. | Trial primary completion date: Feb 2024 --> Feb 2025

P2, N=20, Completed, Protagonist Therapeutics, Inc. | Active, not recruiting --> Completed | Trial primary completion date: Oct 2022 --> Mar 2023

P3, N=50, Enrolling by invitation, Protagonist Therapeutics, Inc. | Not yet recruiting --> Enrolling by invitation

Treatment with rusfertide resulted in rapid, robust, and sustained reduction in HCT levels in PV patients with elevated HCT levels at baseline. Treatment resulted in normalization of iron parameters as noted by increases in ferritin, and normalization of serum iron and MCV in patients who were iron deficient at baseline. Improvements in iron deficiency following rusfertide are suggestive of clinical benefits and merit further investigation.

Studies in patients with PV indicate rusfertide results in rapid, sustained and durable HCT control, independent of patient risk category or concurrent therapy with hydroxyurea, interferon or ruxolitinib. The hemoglobin response tracks rusfertide plasma concentrations. The integrated concentration-hemoglobin relationship showed rapid onset and subsequent maintenance in hemoglobin-time course following initiation ofrusfertide and the loss in effect upon dosing suspension. Hemoglobin, Pharmacokinetic, Polycythemia vera, Rusfertide

These data demonstrate that treatment with rusfertide and analogs, restricts iron from erythropoiesis by sequestering it in macrophage storage compartments. These effects along with normalization of iron homeostasis contribute to usefulness of rusfertide dose titration treatment in maintaining HCT <45% and improving symptoms related to iron deficiency in human PV.

To reduce the incidence of thrombotic events, polycythemia vera (PV) patients are treated with periodic therapeutic phlebotomy (TP) alone or in combination with either hydroxyurea (HU), ruxolitinib (RUX) or interferon (IFN) to maintain hematocrit (HCT) levels below 45% as per NCCN guidelines. These were transient in nature and generally managed by antihistamines. Most of the adverse events were grade 1-2 and there were no drug-related serious adverse events or grade 3 or 4 adverse reactions.