- On Election Day, Arrowhead Pharmaceuticals announced that the U.S. Food and Drug Administration had placed a clinical hold on its Heparc-200 study assessing ARC-520 for treating patients with chronic hepatitis B virus (HBV).
- A clinical hold halts the recruitment of any additional patients for the study and stops all dosing in patients currently enrolled. In its verbal notice, the FDA didn't indicate the clinical hold was based on any human findings, Arrowhead said, and an FDA letter is expected within 30 days.
- The California-based gene-therapy company said its study is on hold while it answers questions "arising from a nonclinical toxicology study in non-human primates using EX1, the company's liver-targeted, intravenously administered delivery vehicle. The cause of these animal deaths is unknown and under investigation."
In September 2015, Jefferies analysts projected that Arrowhead's ARC-520 could potentially reach $4.5 billion in annual sales by 2020 if approved.
So it came as a surprise when the company made an under the radar announcement about the clinical hold.
"While Arrowhead does not expect the hold to delay progress of any of its programs, until proven it's safe, we take a cautious view," wrote Jefferies analyst Eun Yang in a note to investors. Yang pointed out that there were no deaths in rats given a higher dose, and that the dose of the delivery vehicle EX1 used in the study was higher than that used in humans or in any prior toxicology studies in animals.
In its Nov. 8 announcement, Arrowhead stressed that EX1 has been administered 800-plus times in more than 300 patients to date. EX1 is also used as the delivery vehicle in its ARC-521 and ARC-AAT programs. Across this "substantial clinical experience," Arrowhead said, only three serious adverse events have been observed, including two fevers treated with acetaminophen (after which the patients continued on the study with no further complications); and a case of hepatic carcinoma in a patient with chronic HBV and cirrhosis, which the treating physician determined was unrelated to the drug.
Arrowhead said it remains committed to working collaboratively with regulatory authorities worldwide, and has disseminated data from the animal study to agencies across its development programs, along with updates. "The company believes the findings in animal toxicology studies are related to dose level, and that the safety profile seen in human clinical studies across the three programs involving EX1 supports continuing all ongoing clinical studies, Arrowhead stated.