The drug - Arc-520 - is one of two RNA based therapies Arrowhead has developed to treat HBV patients. It is designed to stop viral gene expression and help patient immune systems to fight the virus.
Arrowhead announced the Phase IIb study had been placed on clinical hold last week, after reporting that several primates had died in a toxicology study of the Arc-520 administered using its synthetic delivery vehicle, Ex1.
The firm said it “has not yet received written notice of the clinical hold from the FDA; however, based on verbal communications the clinical hold was prompted by deaths at the highest dose of an ongoing non-human primate toxicology study.”
It added that: “This study involves higher doses of EX1 than those used clinically in humans and higher than those used in the company's previous animal toxicology studies. The cause of these animal deaths is unknown and under investigation.”
Ex1 is made up of dynamic polyconjugates (DPCs), which are synthetic polymers designed to mimic the features viruses possess to get the siRNA into target tissue cells. The tech is used in the company's ARC-520, ARC-521, and ARC-AAT programs.
Amgen licensed development rights to two drug candidates delivered using the Ex1 platform in a deal in September.
To date, EX1 has been administered over 800 times in more than 300 human study subjects and patients according to Arrowhead, which said that three serious adverse events had been observed.
“Two of these were fevers, treated with acetaminophen, after which the patients continued on the study with no further complications. The other SAE was an instance of hepatic carcinoma in a patient with chronic HBV and cirrhosis, judged by the treating physician to be unrelated to the drug.”
Arrowhead declined to comment.