FDA Lifts Hold on Protagonist’s Clinical Program Treating Disorders of Red Blood Cells

The U.S. Food and Drug Administration lifted the full clinical hold on the company’s rusfertide, its experimental therapy for red blood cell disorders.

Photo: Dinesh Patel, president and CEO of Protagonist

News of the lift, which was place on rusferitide in September, sent shares of Protagonist soaring prior to the market’s opening to more than $34 a share, more than an 85 percent increase.

The company said it provided the FDA with all requested information as the basis for a Complete Response and subsequent removal of the clinical hold. In particular, the company provided the requested individual patient clinical safety reports, updated the investigator brochure and patient informed consent forms, performed a comprehensive review of the most recent safety database, and included new safety and stopping rules in the study protocols.

Protagonist said it is working closely with study investigators and clinical trial sites to resume dosing of patients in ongoing clinical trials with rusfertide after patients have been reconsented.

The clinical hold was triggered by a recent non-clinical finding in a 26-week rasH2 transgenic mouse model indicating benign and malignant subcutaneous skin tumors. The rasH2 signal also prompted a re-examination of the four cases of cancer observed across all rusfertide clinical trials involving more than 160 patients, and a comprehensive review of the safety database, including cases of suspected unexpected serious adverse reactions (SUSAR). No additional cancer cases, and no other unexpected safety signals, surfaced in this process.

The clinical hold followed Protagonist’s notification to the FDA of a recent non-clinical finding in a 26-week rasH2 transgenic mouse model study. The rasH2 model is designed to detect signals related to tumorigenicity, and benign and malignant subcutaneous skin tumors were observed in this study.

Protagonist is developing rusfertide as a treatment for polycythemia vera, a rare myeloproliferative disease characterized by the excessive production of red blood cells. Well-established treatment guidelines focus on maintaining hematocrit levels continuously below 45 percent to reduce the risk of thrombotic events, but treatments are unable to maintain hematocrit to below the 45 percent target for many patients and may be associated with serious side effects. There are an estimated 100,000 patients with polycythemia vera in the United States and approximately 100,000 patients in major EU countries.

Rusfertide is an investigational, injectable synthetic mimetic of the natural hormone hepcidin that regulates iron homeostasis and controls the absorption, storage, and distribution of iron in the body. The company is studying rusfertide in a phase 2 proof-of-concept clinical trial for polycythemia vera (PV), a phase 2 study in PV subjects with high hematocrit levels, and a phase 2 study for hereditary hemochromatosis.

“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.,” said Dinesh Patel, president and CEO of Protagonist. “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.”

Author: Rare Daily Staff