Arrowhead Research Corporation, a biopharmaceutical company currently developing targeted RNAi therapeutics, recently announced that the United States Food and Drug Administration (FDA) has granted orphan drug designation for its experimental ARC-AAT therapy. ARC-AAT is the company’s RNAi-based therapeutic candidate currently under evaluation as a viable treatment for Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disease that severely damages both the lungs and liver of those affected (children and adults alike). Arrowhead is conducting part B of a Phase 1 study for ARC-AAT in patients with the PiZZ genotype of AATD.

“Receiving orphan drug designation is an important milestone in the development of ARC-AAT which we think is a very promising program aimed at providing a better option for patients with liver disease associated with alpha-1 antitrypsin deficiency. The Orphan Drug Act provides important incentives for sponsors to develop drugs that treat rare diseases and we look forward to more engagement with the FDA as the development of ARC-AAT progresses,” noted Bruce D. Given, who is Arrowhead’s Chief Operating Officer.

The ongoing Phase 1 trial for ARC-AAT is a randomized, multi-center, double-blind, placebo-controlled, single dose-escalation, and the first study in a human trial to assess the safety, pharmacokinetics and tolerability of ARC-AAT as well its effects on circulating AAT levels. The study enrolled dose cohorts including 6 participants each and participants were randomly distributed at a ratio of 2:1 (active versus placebo) to receive one intravenous injection of ARC-AAT or the placebo (composed of saline solution). In a previous phase 1 trial, the study was focused on evaluating healthy patients, and then on assessing patients with PiZZ genotype AATD. Participants in this study were evaluated for 28 days.

AATD is linked to pulmonary disease in adults and it is an autosomal recessive genetic disorder. Alpha-1 antitrypsin is a circulating glycoprotein protease that inhibits production of serpin in the liver, which is encoded by the gene AAT. It also inhibits neutrophil proteases in order to protect healthy tissues in inflammatory situation and prevents damage of the tissue. The disease is connected to continuous hepatocyte injury that can lead to fibrosis cirrhosis and a higher risk of hepatocellular carcinoma.