In quick turnaround, FDA lifts full clinical hold on Protagonist's blood cancer program
Not even a month after being slapped with a full clinical hold on all studies related to a blood cancer program, Protagonist Therapeutics saw regulators reverse course.
Protagonist’s experimental drug rusfertide is cleared to resume dosing in all studies, the biotech announced Monday morning, paving the way for researchers to launch a Phase III trial in polycythemia vera early next year. The move comes exactly 25 days after the FDA halted rusfertide studies due to skin tumors arising in mice treated with the drug.
“Depending upon each site’s and local rules, we expect dosing in most patients to resume as rapidly as possible,” CEO Dinesh Patel said in an investor call Monday morning.
Investors jumped for joy at the news, sending Protagonist shares $PTGX skyrocketing more than 90% in pre-market trading from $18.24 to the mid-$30 range. After the market opened, shares were up nearly 100%. It marked a nearly equal and opposite reaction to the stock’s movement after the hold was announced, when shares fell from $46 to $18 in a day.
To get things back up and running, Protagonist will need to make a couple of changes to its Phase II studies and planned Phase III trial, the biotech said. In the Phase II polycythemia vera programs, researchers are adding new cancer surveillance guidelines, regular skin exams and procedures to stop the studies again if necessary.
In the Phase III trial, Protagonist will be required to modify its enrollment criteria to only include patients who have been cancer-free for at least five years before the study, a change Patel said won’t affect the study’s timeline or overall recruitment. The CEO added that the biotech will not need to conduct or launch any additional preclinical or clinical rusfertide studies.
Patel credited the biotech’s largely silent approach to getting the hold resolved so quickly, as Protagonist revealed little data about the mouse model and human cancer cases last month. But he went into more detail on Monday, outlining why the FDA saw reason to halt all rusfertide trials and detailing four cases of cancer from clinical studies.
Specifically, the mouse model involved is set up to detect how carcinogenic and toxic the drug is, and how its effects in mice could translate to humans — a standard process in drug development. The model is designed to measure for many different types of cancer signals, but most mouse tumors occurred subcutaneously in the skin, proving to be benign.
All the mouse tumors also took place at dosing levels much higher than the human dose, chief scientific officer David Liu said on Monday’s call, and “just barely” reached the statistical significance threshold for correlation to treatment. There were two instances of malignant tumors in the mice, but significance was only measured using combined findings of malignant and benign tumors, Liu said.
In humans, two of the four cancer cases arose during polycythemia vera studies, one during a hereditary hemochromatosis trial and one in a beta thalassemia study. Only the cases stemming from the polycythemia vera trials were viewed as possibly related to rusfertide after the mouse model picked up the tumor signals, the biotech detailed.
After investigator review, one case was deemed unrelated to rusfertide while the second is considered to be “unlikely related,” SVP for clinical development Paula O’Connor said on the Monday call.
In a note to investors, SVB Leerink’s Joseph Schwartz described Monday’s update as a “very welcomed surprise” given the hold was announced on Sept. 17. He also noted he was particularly encouraged by the lack of new cancer cases coming from a full safety review for SUSARs of Protagonist’s entire database.
With the Phase III study now planned for the first quarter of next year, Protagonist will be aiming to put this setback fully in the rearview mirror. The clinical hold had been another in a long line of obstacles for the Newark, CA-based biotech, which pivoted to a main focus on rusfertide after axing a former lead program in ulcerative colitis in May 2020.
It had been a seismic shift for Protagonist, as the company spent a decade building its peptide-based platform, and its earliest assets were for IBD.