Rusfertide Clinical Trials to Resume After FDA Lifts Hold


Following a safety evaluation, the FDA has lifter its clinical hold of studies of rusfertide.

Studies involving rusfertide (PTG-300) can continue after the FDA lifted a clinical hold on the agent, according to a press release by Protagonist Therapeutics.1

Rusfertide is an injectable synthetic mimetic of hepcidin, a natural hormone. The synthetic is meant to offer greater potency, stability, and solubility, translating to better outcomes when compared with the natural hormone. Hepcidin regulates iron absorption, distribution, and storage, controlling the body’s production of red blood cells.

"We are extremely pleased that the FDA has acted so quickly in lifting the clinical hold on the rusfertide development program, allowing us to resume patient dosing in our clinical studies," said Dinesh Patel, PhD, president and chief executive officer of Protagonist in a press release. "Patient safety continues to be our topmost priority. We believe that the cumulative evidence regarding the safety and clinical risk-benefit of rusfertide is supportive of expedited clinical development. We are actively preparing to initiate the phase 3 registrational study for polycythemia vera in the first quarter of 2022.”

The use of the agent was halted due to non-clinical findings of a 26-week rasH2 transgenic mouse model. The model was meant to detect signals related to tumorigenicity. During the study, both benign and malignant subcutaneous skin tumors were observed. A safety review led to the removal of the FDA hold.2

Rusfertide is currently being investigated in over 160 patients, including in a phase 2 trial of the agent in patients with polycythemia vera (PV; NCT04767802). The interventional, single-group assignment study has an estimated enrollment of 20 participants and an estimated completion date of April 30, 2023. The primary end point of the study is efficacy, evaluated as the rate of patients with hematocrit < 45%. The secondary end point of the study is the rate of treatment-related adverse events at week 52.

During the study, patients with newly diagnosed PV or patients for whom current therapy is not sufficient to control their hematocrit, received rusfertide every 2 to 4 weeks in order to maintain hematocrit < 45%, with a target of < 43%. All patients must have a hematocrit of > 48% prior to dosing. Therapy may be administered up to 52 weeks.

In order to participate in the study, patients must have a known PV diagnosis, evidence of hematocrit > 48% 3 or more times in the 28 weeks before dosing or 5 or more times in the 52 weeks before dosing, with the exception of newly diagnosed patients, and an ECOG score of 0, 1, or 2. Patients with clinically significant thrombosis, active or chronic bleeding within 4 weeks of screening, infection requiring hospitalization, known primary or secondary immunodeficiency, or a history of invasive malignancies within the last 2 years are not eligible to participate.

“Protagonist will continue to work closely with the FDA to ensure patient safety with amendments to current and planned future studies with rusfertide. We remain optimistic about the future potential of rusfertide to address unmet medical needs in excessive erythrocytosis and iron overload related diseases like polycythemia vera and hereditary hemochromatosis, respectively said Patel,” in the press release.


1. Protagonist Therapeutics announces removal of FDA clinical hold on the rusfertide clinical development program. News release. Protagonist Therapeutics, Inc. October 11, 2021. Accessed October 12, 2021.

2. Protagonist Therapeutics reports FDA clinical hold on rusfertide clinical development program. News release. Protagonist Therapeutics, Inc. September 17, 2021. Accessed October 12, 2021.

3. PTG-300 in patients with polycythemia vera and elevated hematocrit. Accessed October 12, 2021.

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