Arrowhead begins transition to patients in Phase I trial of ARC-AAT to treat liver disease

AATD is a rare genetic disorder that can severely damage the liver and lungs of affected individuals.

The trial will start dose escalation in healthy volunteers (Part A) and transition into patients (Part B) when a predefined knockdown target is achieved.

The multi-center, randomized, placebo-controlled, double-blind, single dose-escalation first-in-human Phase I trial was designed to evaluate the safety, tolerability and pharmacokinetics of ARC-AAT and the effect on circulating AAT levels.

The company said that target is at least 30% reduction of serum AAT levels in three subjects or greater than 60% reduction in a single subject, which was met during the third cohort.

All three dose levels tested appear to be generally well tolerated and the data safety committee has cleared the trial to move into patients with AATD.

Dosing in patients may now start at the highest dose level used in Part A and then continued dose escalation may proceed under the protocol.

The company expects to complete the Phase I study by the end of this year.

Arrowhead chief operating officer Bruce Given said: "We are excited that Part A of the phase 1 study is complete and that we can now begin studying ARC-AAT directly in patients with PiZZ genotype AATD.

"The lung disease associated with AATD is frequently treated with AAT augmentation therapy. However, there is a great need in the field to identify new treatment options for the AATD-related liver disease.

"Currently, the only option for severe cases is liver transplant, with all of its attendant risks and availability issues. We think ARC-AAT is a very promising program that may potentially provide a better option for patients and physicians."