FDA places clinical hold on potential HBV drug due to delivery method

Arrowhead Pharmaceuticals announced the company received verbal notification from the FDA of a clinical hold placed on Heparc-2004, the company’s clinical trial of ARC-520, an investigational drug for hepatitis B virus infection.

Per a press release, the FDA decided to place the study on hold due to deaths in an ongoing primate toxicology study using the same delivery method. The company said in the release the FDA did not indicate the clinical hold was based on findings from human clinical trials. The Heparc-2004 study includes up to 12 patients in the U.S.

ARC-520 is an investigational agent where small interfering RNAs within the drug engage the body’s normal cellular RNAi machinery and direct specific cleavage of HBV RNA transcripts, leading to a reduction in the levels of HBV proteins and the RNA template used to produce viral DNA, according to Arrowhead.

In the animal study, primates were given higher-than-normal doses of EX1, the company’s liver-targeted, intravenously administered delivery vehicle. These doses were higher than those used in the company’s previous animal toxicology studies and higher than those given to humans, according to the press release. This delivery vehicle is currently used in the company’s hepatitis B-focused programs looking at ARC-520 and ARC-521, and that looking at ARC-AAT, a drug geared towards the treatment of liver disease associated with alpha-1 antitrypsin deficiency.

To date, EX1 has been given to more than 300 human patients and administered more than 800 times, per the release. Of these, three serious adverse events have been observed; two being fevers that were treated with acetaminophen and patients continued the study with no further complications, and an instance of hepatic carcinoma in a patient with chronic HBV and cirrhosis, deemed by a physician to be unrelated to the drug. Four patients discontinued ARC-520 treatment due to infusion reactions. The company stated all three clinical programs were not indicative of any drug-induced organ toxicity.

The cause of these animal deaths is unknown and under investigation, per the release.

“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 in the release.