Source: Hepatitis News Today Author Daniela Semedo PHD
On 8 November the U.S. Food and Drug Administration (FDA) placed a hold on Arrowhead Pharmaceuticals‘ HEPARC-2004 Phase 2 clinical trial evaluating ARC-520, the company’s investigational medicine for the treatment of chronic hepatitis B virus (HBV) infection.
Arrowhead said in a press release the FDA verbally notified the company of its decision to hold the trial until Arrowhead responds to concerns raised about deaths in non-human primates given the highest dose in an ongoing nonclinical toxicology study using EX1, an intravenously administered delivery vehicle used in the company’s ARC-520, ARC-521, and ARC-AAT programs.
The doses in this study are higher than those used clinically in humans and are higher than used in previous animal toxicology studies, Arrowhead said.
The FDA has not indicated to Arrowhead that the clinical hold was based on any human data.
So far, EX1 has been administered more than 800 times in more than 300 humans with only three serious adverse events (SAE). Two of the events were fevers, and the third was a case of hepatic carcinoma considered not related to the treatment.
To date, 6 percent of infusions in ARC-520 studies have resulted in clinical reactions, with four patients discontinuing treatment. According to the company, across the ARC-520, ARC-521, and ARC-AAT clinical programs, laboratory tests have not shown any drug-induced organ toxicity.
Arrowhead has already reported data from the animal study to regulatory authorities across its development programs and will be providing updates.
Arrowhead said it believes the deaths seen in the animal toxicology studies are related to the high dose level. The company considers the safety profile seen in human clinical trials in its three development programs involving EX1 supports the continuation of its ongoing trials.
The Heparc-2004 Phase 2 clinical trial (NCT02452528) is evaluating the reduction of the hepatitis B surface antigen (HBsAg) after intravenous administration of ARC-520 in combination with 0.5 or 1.0 mg per day of Baraclude (entecavir) or 300 mg per day of Viread (tenofovir) in HBV patients.
Patients were randomized to 1.0 mg/kg ARC-520 once every four weeks for a total of three doses or a placebo. The clinical trial is being conducted on up to 12 patients in the U.S.
ARC-520 is an RNAi-based candidate being developed as a cure for chronic HBV infection. The goal is to reach an immune clearant state in patients, which is characterized by a serum negative for hepatitis B s-antigens.
It has recently been suggested that related trial sites in Australia may no longer be recruiting trial participants.
If you are currently participating in this trial you should seek further clarifications from your treating doctor.