Clinical Hold Placed on Hepatitis B Drug Trials

Arrowhead Pharmaceuticals recently announced that the FDA placed a clinical hold on the Heparc-2004 clinical trial, which is exploring an investigational hepatitis B virus treatment.

Heparc-2004 is a multicenter, randomized, double-blind, placebo-controlled, multi-dose study of ARC-520 in 12 patients with chronic hepatitis B virus under an investigational new drug, according to a press release from Arrowhead. They are currently evaluating the drug in phase 2b dose and combination clinical studies.

ARC-520 is an investigational hepatitis B virus drug that intervenes upstream of the reverse transcription process where nucleotide and nucleoside analogs act, and also inhibits the creation of hepatitis B virus gene products, according to the press release.

The drug is being studied to determine whether reducing circulating and non-circulating viral proteins and RNA could increase the immune response, and cure the infection.

The company must now provide additional information about questions that resulted from a nonclinical toxicology study in animal models using EX1, an intravenously administered delivery vehicle, according to the press release.

However, the FDA did not say that the hold was related to any findings in humans. EX1 has been used more than 800 times in over 300 human patients, and only 3 serious adverse events were experienced.

EX1 is used as a delivery vehicle in the ARC-520, ARC-521, and ARC-AAT clinical programs, Arrowhead reported.

In the studies, 2 patients developed fevers that were promptly treated with acetaminophen, and they continued treatment without experiencing other serious adverse events. The other patient developed hepatic carcinoma, which was determined to be unrelated to the drug, according to the press release. There were 4 patients who discontinued treatment with ARC-520 due to infusion reactions.

Other common adverse events include upper respiratory infection and headache.

Based on verbal communications with the FDA, Arrowhead believes that the clinical hold was implemented due to deaths at high doses of the drug in a non-human primate toxicology trial. This study involves using a higher dose of EX1 than is used in humans, and is also higher than doses used in other animal toxicology studies.

The reason behind the high number of deaths is currently unknown and is being explored. They believe that these findings are due to the dose, and that the safety profile in human clinical studies is consistent across the 3 developmental programs that involved EX1.

Arrowhead is committed to working closely with the FDA and regulatory authorities worldwide, the press release concluded.