Protagonist Therapeutics announced Monday morning that the FDA had removed the hold on PV drug candidate rusfertide, clearing the way for all trials to resume.
After having its studies of PV drug candidate rusfertide placed on a clinical hold just over three weeks ago, Protagonist Therapeutics is enjoying a swift resolution to the dilemma. The company announced Monday morning that the U.S. Food and Drug Administration (FDA) had removed the hold, clearing the way for trials to resume.
The clinical hold was due to the development of tumors in mice in a non-clinical study. The concurrent study, which utilized a rasH2 transgenic mouse model designed to detect signals related to tumorigenicity, alerted the Newark, Calif.-based biopharma to a potential risk of benign and malignant subcutaneous skin tumors. Protagonist, in turn, informed the FDA, and dosing in all studies of rusfertide was paused.
Protagonist is hoping that Rusfertide (PTG-300), a novel injectable synthetic mimetic of the natural hormone hepcidin, will translate to better in vivo PK and PD characteristics in comparison. It is being developed for PV, a rare type of blood cancer characterized by the increased production of red blood cells. Current treatment options have failed to maintain hematocrit below the 45% target for many patients and may be associated with severe side effects. The disease is rare, affecting 44 to 57 patients per 100,000 people in the United States.
After providing the FDA with individual patient clinical safety reports, updating the investigator brochure and patient informed consent forms and performing a comprehensive review of the most recent safety database, the regulator gave the go-ahead for all trials to resume. Protagonist said that it also included new safety and stopping rules in the study protocols. Four cases of cancer observed out of 160 patients across all clinical trials were further scrutinized. The review revealed no additional cases of cancer or any other unexpected safety signals. The company is now back on track to begin a phase III registration trial in the first quarter of 2022.
“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,” Protagonist President and CEO Dinesh Patel, Ph.D., said in a statement. “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.”
In June, Protagonist presented updated phase II data from the rusfertide program at the European Hematology Association 2021 Virtual Congress. The results, reflective of 63 patients treated with the drug, 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, with the most common adverse effects being transient injection site reactions.
“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,” Patel stated, adding that Protagonist will continue to work closely with the FDA to ensure patient safety with amendments to current and planned future studies of the drug.
After falling by over 60% on news of the hold, Protagonist’s stock has rebounded, surging by 89.4% to near 34.50 on Monday morning. SVB Leerink analyst Joseph Schwartz said the news “comes as a very welcome surprise,” considering how rusfertide was placed on hold recently.
