OSAKA, JAPAN & PASADENA, CALIF.-- June 28, 2022 -- Takeda (TSE:4502/NYSE:TAK) (“Takeda”) and Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that results from a Phase 2 clinical study (AROAAT-2002) of investigational fazirsiran (TAK-999/ARO-AAT) for the treatment of liver disease associated with alpha-1 antitrypsin deficiency (AATD) were recently published in the New England Journal of Medicine (NEJM) and presented in an oral presentation at The International Liver Congress™ 2022 - The Annual Meeting of the European Association for the Study of the Liver (EASL). The NEJM article was published online ahead of print and is titled, “Fazirsiran for Liver Disease Associated with Alpha-1 Antitrypsin Deficiency.” The EASL presentation was titled, “Reduction of Intra-hepatic Z-AAT Synthesis by Fazirsiran Decreases Globule Burden and Improves Histological Measures of Liver Disease in Adults with Alpha-1 Antitrypsin Deficiency.”

“There is currently no specific treatment for liver disease associated with AATD. The results from the AROAAT-2002 study provide multiple lines of evidence that preexisting liver damage in these patients may be meaningfully improved following treatment with fazirsiran,” said Pavel Strnad, M.D., Professor at University Hospital RWTH Aachen and principal investigator of the AROAAT-2002 study who presented the data at EASL. “Specifically, the improvements in histological globule burden, reduction in histological signs of portal inflammation, normalization of elevated liver enzymes, and improvement in liver fibrosis are all encouraging indicators that fazirsiran may rapidly ameliorate liver injury. It also speaks to the exciting innovation going on in the field, that an siRNA therapeutic specifically targeted into the liver has the potential to address a previously untreatable liver disease.”

Fazirsiran is a potential first-in-class investigational RNA interference (RNAi) therapy designed to reduce the production of mutant alpha-1 antitrypsin protein (Z-AAT) as a potential treatment for the rare genetic liver disease associated with AATD. Z-AAT accumulation is believed to be the cause of progressive liver disease in patients with AATD. Reducing production of the inflammatory 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 (BTD) in July 2021 and Orphan Drug Designation in February 2018 for the treatment of AATD from the US FDA.

“The exciting data on fazirsiran treatment from the open label AROAAT-2002 Phase 2 study in patients with AATD liver disease suggest a treatment effect and the potential to improve multiple downstream markers of liver health. We are also nearing completion of the Phase 2 SEQUOIA study and we look forward to further assessing the potential of fazirsiran in this larger placebo-controlled study,” said Javier San Martin, M.D., Chief Medical Officer at Arrowhead. “Fazirsiran has shown a high level of activity across all patients studied and is representative of how the RNA interference pathway can be leveraged to reliably and consistently silence gene expression and potentially have a positive impact on patients with various genetic diseases.”

“These early results demonstrate the potential for an RNAi therapy like fazirsiran to reverse liver disease in patients with AATD liver disease and we are hopeful fazirsiran will one day help patients avoid the need to undergo liver transplantation,” said Chinwe Ukomadu, M.D., Ph.D., Head, Gastroenterology Therapeutic Area Unit at Takeda. “We look forward to continuing our successful collaboration with Arrowhead and applying Takeda’s long history of innovation in gastroenterology to initiate a Phase 3 study of fazirsiran.”