Protagonist’s PV Drug Placed on Hold After Mice Develop Tumors


A transgenic mouse model has done its job in a study of Protagonist Therapeutics’ rusfertide, which is currently in clinical development for the treatment of polycythemia vera (PV). The company announced Friday that clinical studies have been placed on hold following the development of tumors in mice in a non-clinical study.

The U.S. Food and Drug Administration (FDA) placed the hold after mice in the 26-week rasH2 study developed both benign and malignant subcutaneous skin tumors after being treated with the drug candidate. The model was designed to detect signals related to tumorigenicity.

Rusfertide (PTG-300) is a novel injectable synthetic mimetic of the natural hormone hepcidin that the company claims offer greater potency, solubility, and stability. Protagonist, which is developing peptide-based new chemical entities for conditions with high unmet need, hopes that rusfertide will translate to better in vivo PK and PD characteristics in comparison to the natural hormone.

PV, a rare type of blood cancer, is characterized by the increased production of red blood cells. Current treatment options for the illness have failed in maintaining hematocrit to below the 45% target for many patients and may be associated with serious side effects. The disease is rare, affecting 44 to 57 patients per 100,000 people in the U.S.

Protagonist had previously informed the FDA of the study results and stated Friday that it is working with the regulator to update clinical study documents and determine the next steps.

“Patient safety is our absolute top priority," said Protagonist President and Chief Executive Officer Dinesh Patel. “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.”

Protagonist added that it would “provide additional clinical safety reports, update the investigator brochures and patient informed consent forms, and make necessary modifications to study protocols.”

In June, Protagonist presented updated phase II data supporting the long-term efficacy of rusfertide in PV at the European Hematology Association 2021 Virtual Congress. The results, reflective of 63 patients treated with rusfertide, demonstrated sustained hematocrit control, reversal of iron deficiency and a reduction of therapeutic phlebotomies in both low and high-risk individuals. Rusfertide was well-tolerated in the study with the most common adverse events being transient injection site reactions.

“This data set cumulatively builds on previously presented scientific evidence demonstrating rusfertide's potential as the first-in-class, non-cytoreductive treatment option for polycythemia vera, a disease that currently has limited therapeutic options and a demonstrated significant unmet medical need,” Patel said at the time.

He further added that this durability and symptom improvement supported the advancement of rusfertide into Phase III clinical development in early 2022.

The current study is designed to monitor the safety profile and determine the effectiveness of rusfertide in patients who require frequent phlebotomies. It also consists of an open-label extension for up to three years to monitor long-term safety and other effects.

With the news, Protagonist’s stock fell 62% on Friday to 17.53.

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