First Patient Treated in Alpha-1 Antitrypsin Deficiency Liver Disease Phase 3 Study Triggering $40 Million Milestone Payment from Takeda to Arrowhead

Arrowhead Pharmaceuticals today announced that the first patient has been dosed in Takeda’s Phase 3 REDWOOD clinical study of fazirsiran (TAK-999/ARO-AAT) for the treatment of alpha-1 antitrypsin deficiency-associated liver disease (AATD-LD). The start of this pivotal study triggers a $40 million milestone payment from Takeda to Arrowhead.

Fazirsiran is an investigational RNA interference (RNAi) therapy designed to reduce the production of mutant alpha-1 antitrypsin protein (Z-AAT) as the first potential treatment for AATD-LD, a rare genetic disease. Z-AAT accumulation is believed to be the cause of progressive liver disease in patients with alpha-1 antitrypsin deficiency (AATD). Reducing production of the mutant Z-AAT protein is expected to halt the progression of liver disease and potentially allow the liver to regenerate and repair. Fazirsiran was granted Breakthrough Therapy Designation in July 2021 and Orphan Drug Designation in February 2018 for the treatment of AATD-LD from the U.S. Food and Drug Administration.

The REDWOOD (TAK-999-3001) clinical study (NCT05677971) is a randomized, double-blind, placebo-controlled, Phase 3 trial to evaluate the efficacy and safety of fazirsiran in the treatment of alpha-1 antitrypsin deficiency-associated liver disease. Approximately 160 adult patients with METAVIR stage F2 to F4 fibrosis will be randomized 1:1 to receive fazirsiran or placebo. The primary endpoint of the study is a decrease from baseline of at least 1 stage of histologic fibrosis METAVIR staging in the centrally read liver biopsy done at Week 106 in patients with METAVIR stage F2 and F3 fibrosis. The REDWOOD study is now recruiting across several sites in the U.S.