Prothena Corporation plc announced that the company has earned a $40 million milestone payment from Novo Nordisk related to the continued advancement of NNC6019 (formerly PRX004) in a Phase 2 clinical study for the treatment of ATTR cardiomyopathy. There remains a high unmet medical need in moderate to advanced ATTR amyloidosis patients at high risk for early mortality due to amyloid deposition in vital organs. Under the terms of the agreement, Prothena is eligible to receive up to $1.2 billion dollars upon achievement of several clinical development and sales milestones, including the $100 million earned to date.

Novo Nordisk gained full worldwide rights to the intellectual property and related rights of the ATTR amyloidosis business and pipeline it acquired from Prothena in July 2021. NNC6019 (formerly PRX004) is an investigational antibody designed to deplete amyloid associated with disease pathology in hereditary and wild type ATTR amyloidosis, without affecting the native, normal tetrameric form of the protein. NNC6019's proposed mechanism of action is to deplete both the deposited amyloid to improve organ function and circulating non-native TTR to prevent further organ deposition.

In preclinical studies, PRX004 demonstrated ability to inhibit amyloid fibril formation, bind soluble aggregate forms of non-native TTR and promote clearance of insoluble amyloid fibrils through antibody-mediated phagocytosis. This differentiated depleter mechanism of action could be developed as a monotherapy approach to ATTR amyloidosis and might also complement existing therapeutic approaches which either stabilize or reduce production of the native TTR tetramer. Prior to Novo Nordisk's acquisition in 2021 of Prothena's ATTR amyloidosis program, Prothena completed a Phase 1 study with PRX004 in patients with hereditary forms of ATTR, in which PRX004 was found to be safe and well tolerated.

In August 2022, Novo Nordisk initiated a Phase 2 trial with NNC6019. The 52-week trial is investigating safety and efficacy of NNC6019 in 99 people with transthyretin amyloid cardiomyopathy.