Clinical study of ARC-AAT for LD associated with AATD begins

Arrowhead Pharmaceuticals Inc. announced it began a phase 2 clinical study of its ARC-AAT, an investigational RNA interference-based drug for the treatment of liver disease associated with alpha-1 antitrypsin deficiency.

According to the company, ARC-AAT works to knock down the alpha-1 antitrypsin gene transcript and reduce the hepatic production of the mutant AAT protein. Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder associated with liver disease in children and adults and pulmonary disease in adults.

“There remains no medical treatment for liver disease associated with AATD, which is increasingly being recognized by patients and physicians as a serious problem,” Bruce Given, MD, chief operating officer and head of research and development at Arrowhead, said in the release. “[This study should give] the first insights into whether ARC-AAT can stop the progression of liver disease and possibly even allow the liver to recover and heal existing damage. This would be a significant breakthrough.”

Given said the multiple dose-escalation, open-label and multi-center study comprising up to 12 patients will assess safety, endurance and effect of multiple, increased doses of ARC-AAT on levels of circulating and intrahepatic alpha-1 antitrypsin as evidenced by changes in liver biopsy in patients with AATD. Researchers will examine two different cohorts of patients’ reaction to 4 mg/kg and 6 mg/kg doses. The patients will also get a pre-dose biopsy, a dose of ARC-AAT every 28 days until seven doses are taken and a post-dose biopsy conducted at 183 days. Patients will come from Canada, Sweden and Ireland, with other locations added pending regulatory and ethics review.

The FDA granted ARC-AAT orphan drug designation last year. – by Janel Miller

Disclosure: Given is employed by Arrowhead.