FDA Places Hold on Protagonist’s Blood Disorders Program after Skin Tumors Observed in Mouse Study

The U.S. Food and Drug Administration placed a clinical hold on Protagonist Therapeutics’ rusfertide program, an experimental therapy in development for disorders of red blood cells, sending shares plummeting 56 percent in premarket trading.

Photo: Dinesh Patel, president and CEO of Protagonist

The clinical hold follows 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.

Rusfertide (PTG-300) 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. It is currently being studied in a phase 2 proof-of-concept clinical trial for polycythemia vera (PV), a rare chronic blood disorder, a phase 2 study in PV subjects with high hematocrit levels, and a phase 2 study for hereditary hemochromatosis.

Polycythemia vera is 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 they 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.

Protagonist is working with the FDA and will be prepared to make all appropriate updates to clinical study documents and determine the next steps in consultation with the FDA. The company says it will provide additional clinical safety reports, update the investigator brochures and patient informed consent forms, and make necessary modifications to study protocols. Dosing of patients in all ongoing clinical trials with rusfertide will be put on hold, and study investigators have been contacted to facilitate patient notification.

“Patient safety is our absolute top priority,” said Dinesh Patel, president and CEO of Protagonist. “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.”

The FDA has previously granted rusfertide Orphan Drug, Fast Track, and Breakthrough Therapy designations.

Author: Rare Daily Staff