RARE Daily

Takeda Strikes $1 Billion Collaboration with Arrowhead for Rare Liver Disease Therapy

October 8, 2020

Rare Daily Staff

Takeda Pharmaceutical and Arrowhead Pharmaceuticals announced a collaboration and licensing agreement to develop Arrowhead’s experimental RNA interference therapy ARO-AAT as a treatment for a rare genetic liver disease associated with alpha-1 antitrypsin deficiency.

As part of the collaboration, Arrowhead will receive $300 million in an upfront payment and up to $740 million in potential development, regulatory and commercial milestone payments.

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease that results in a lack of the protein AAT and can cause lung disease and liver disease as a result. Alpha-1 antitrypsin-associated deficiency (AATD) is a rare genetic disorder associated with liver disease in children and adults and pulmonary disease in adults. AATD is estimated to affect 1 per 3,000-5,000 people in the United States and 1 per 2,500 in Europe. The protein AAT is primarily synthesized and secreted by liver hepatocytes. Its function is to inhibit enzymes that can break down normal connective tissue. The most common disease variant, the Z mutant, results in improper folding of the protein. The mutant protein cannot be effectively secreted and accumulates in globules inside the hepatocytes, triggering continuous hepatocyte injury, leading to fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma. Liver transplant is currently the only available cure.

Arrowhead’s ARO-AAT, currently in phase 2 studies, is designed to knock down the hepatic production of the mutant alpha-1 antitrypsin protein, halt the progression of liver disease, and potentially allow it to regenerate and repair.

“AAT-associated liver disease is a devastating condition for which there are no approved therapies. With its RNAi-based mechanism of action, ARO-AAT has the potential to treat the underlying cause of AATLD, thereby helping patients avoid the need for liver transplantation and associated co-morbidities,” said Asit Parikh, head, Gastroenterology Therapeutic Area Unit at Takeda.

Under the terms of the agreement, Takeda and Arrowhead will co-develop ARO-AAT, which, if approved, will be co-commercialized in the United States under a 50/50 profit-sharing structure. Outside the United States, Takeda will lead the global commercialization strategy and receive an exclusive license to commercialize ARO-AAT with Arrowhead eligible to receive tiered royalties of 20-25 percent on net sales.

“Takeda’s global presence and experience with payers and regulators in the rare disease and GI therapy space, combined with its long history serving the Alpha-1 community make it the ideal partner for ARO-AAT,” said Christopher Anzalone, president and CEO at Arrowhead. “It is well-positioned to work with the patient and medical community to help meet the severe unmet need of patients with Alpha-1 liver disease.

Photo: Christopher Anzalone, president and CEO at Arrowhead

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