Clinical Hold on Development of Rusfertide Removed by FDA


Clinical trials featuring rusfertide may resume dosing patients after the FDA lifted a full clinical hold on the therapy’s clinical studies.

The FDA has removed its full clinical hold on clinical studies of rusfertide (formerly PTG-300) and all dosing with the agent may resume, according to a press release from developer Protagonist Therapeutics.1

The organization provided the FDA the necessary information outlined in a complete response letter to remove the clinical hold, including patient clinical safety reports, an updated investigator brochure, and updated patient consent forms. Investigators also conducted a comprehensive review of the most recent safety database and outlined new safety and stopping rules in the study protocols. Protagonist Therapeutics is currently working with investigators to assist clinical trial sites resume dosing patients who are enrolled in clinical trials with rusfertide following reconsent.

“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,” Dinesh Patel, PhD, president and chief executive officer of Protagonist Therapeutics, said 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.

“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.”

The full clinical hold was issued on September 17, 2021, following nonclinical data from a 26-week rasH2 transgenic mouse model that identified benign and malignant subcutaneous skin tumors.2 The rasH2 signal also resulted in a re-examination of 4 cancer cases across all clinical trials featuring rusfertide, which included more than 160 patients, as well as a comprehensive review of the safety database. The review included factors such as suspected unexpected serious adverse effects. Notably, no additional cancer cases or other unexpected safety signals were noted during this process.

“Patient safety is our absolute top priority,” Patel explained. “We are fully committed to working closely with the FDA in understanding and evaluating potential clinical risks and determining next steps for the development of rusfertide.”

Rusfertide previously received a breakthrough therapy designation in June 2021 to reduce erythrocytosis among patients with polycythemia vera who do not require further treatment for thrombocytosis of leukocytosis.3 Additionally, the designation is granted to treatments that address serious or life threatening conditions and requires preliminary clinical data highlighting a substantial improvement over existing therapies on 1 or more clinically significant end points.

The designation was based on promising findings from an ongoing phase 2 study (NCT04767802) of rusfertide in patients with polycythemia vera and elevated hematocrit. Data from the trial indicated that most patients were able to eliminate therapeutic phlebotomies and maintain a target hematocrit level lower than 45%. Moreover, the treatment helped to repair iron deficiency and improve disease symptoms.


  1. Protagonist Therapeutics announces removal of FDA clinical hold on the rusfertide clinical development program. News release. Protagonist Therapeutics. October 11, 2021. Accessed October 12, 2021.
  2. Protagonist Therapeutics reports FDA clinical hold on rusfertide clinical development program. News release. Protagonist Therapeutics. September 17, 2021. Accessed October 12, 2021.
  3. Protagonist Therapeutics receives FDA breakthrough therapy designation for rusfertide in polycythemia vera. News release. Protagonist Therapeutics. June 3, 2021. Accessed October 12, 2021.
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