Arrowhead Pharmaceuticals announced the first patient treated in Takeda’s phase 3 REDWOOD trial of fazirsiran (TAK-999/ARO-AAT) for patients with alpha-1 antitrypsin deficiency (AATD)-associated liver disease (AATD-LD).

The study start, announced via news release, triggered a $40 million payment from Takeda to Arrowhead.

AATD is a rare autosomal dominant condition in which a genetic mutation leads to abnormally folded AAT protein (Z-AAT), which is thus unable to be released into the bloodstream for transport to the lungs. Normally, AAT inhibits enzymes that breakdown connective tissue, protecting lung tissue from inflammation and irritants such as tobacco smoke. AATD affects approximately 1 in 3000 to 5000 individuals in the US.

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In AATD, because the Z-AAT protein cannot be released into the bloodstream, it accumulates in the liver, leading to fibrosis, cirrhosis, and, potentially, liver cancer. Approximately 35% of patients with AATD develop liver disease. The absence of Z-AAT in the lungs contributes to the development of chronic lung inflammation and acute lung injury. AATD-LD is progressive and can affect patients of any age, including infants and children.

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Fazirsiran is an investigational RNA interference (RNAi) compound aimed at reducing production of Z-AAT, thereby giving the liver the opportunity to regenerate and recover. The US Food and Drug Administration (FDA) granted fazirsiran Orphan Drug Designation in 2018 and Breakthrough Therapy Designation in 2021 specifically for the treatment of AATD-LD.

The REDWOOD trial is a phase 3, randomized, double-blind, placebo-controlled trial of fazirsiran efficacy and safety in approximately 160 patients over age 18 who have Metavir stage F2 to F4 fibrosis of the liver.

The primary outcome measure of REDWOOD is a reduction from baseline in fibrosis by at least 1 stage as determined by liver biopsy at week 102. The study is currently recruiting patients in the US.


First patient treated in alpha-1 antitrypsin deficiency liver disease phase 3 study triggering $40 million milestone payment from Takeda to Arrowhead. News release. Arrowhead Pharmaceuticals; April 4, 2023.