Protagonist's PV Breakthrough Designation on the Line

FDA_Sarah Silbiger/Getty Images

Sarah Silbiger/Getty Images

Shares of Protagonist Therapeutics are plunging after the company announced in a filing that the U.S. Food and Drug Administration may rescind the Breakthrough Therapy Designation it awarded rusfertide last year as a potential treatment for patients with polycythemia vera (PV) for the reduction of erythrocytosis. 

In a filing with the U.S. Securities and Exchange Commission, California-based Protagonist disclosed the regulatory agency issued a letter of intent to rescind the status based on concerns first raised in a clinical hold placed on the drug candidate last year. 

Protagonist said it intends to meet with the regulatory agency to discuss the potential rescinding of the designation. When it meets with the FDA, Protagonist will provide a briefing document on why the company believes the designation should not be rescinded. The company was quick to note that the FDA has not indicated that it intends to revoke the Fast Track designation awarded to rusfertide.

Breakthrough Therapy designation had been awarded last year based on Phase II data that showed the majority of patients who were treated with rusfertide were able to eliminate therapeutic phlebotomies and maintain a target hematocrit level of less than 45%. Also, data presented at the American Society of Hematology meeting in 2020 showed that rusfertide patients were also able to reverse iron deficiency and saw improvements in disease symptoms. 

At the 2021 meeting of ASH, Protagonist presented data that confirmed the drug's efficacy, particularly noting the impact on phlebotomy-dependent PV patients. During the first 28 weeks of treatment, 84% of patients required no phlebotomies. 

At the time of the awarding of Breakthrough Therapy Designation, Protagonist Chief Development Officer Suneel Gupta said that rusfertide is a natural hormone mimetic that "may stand out as the first non-cytoreductive therapeutic drug for PV," a rare blood cancer that is characterized by an increased production of red blood cells. Rusfertide is currently in a Phase III study in polycythemia vera. Protagonist noted in its SEC filing that no changes to the development plan or timeline are anticipated at this stage.

Months after the FDA awarded Breakthrough Therapy to rusfertide, the experimental drug was hit with a clinical hold after mice being assessed in a non-clinical study of the asset developed tumors. As BioSpace previously reported, the mice developed benign and malignant subcutaneous skin tumors following treatment with the drug candidate.

One month after the hold was placed, the FDA lifted it after Protagonist provided the regulatory agency with individual patient clinical safety reports and updates to the investigator brochure and patient informed consent forms and performed a comprehensive review of the safety database. The review revealed no additional cases of cancer or any other unexpected safety signals. 

In its filing, the company has updated the corporate presentation of rusfertide that included details of the cancer cases. Out of 168 patients dosed with the drug, there have been eight reported cases of cancer in seven patients. Those cases were inclusive of preexisting cases. 

The company also included new safety and stopping rules in the study protocols for rusfertide, the company announced last year. 

Shares of Protagonist were down more than 22% in premarket trading to $19.67. The stock closed at $201.6 on Wednesday. 

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