AstraZeneca and Ionis sign deal to develop and commercialise eplontersen, formerly known as IONIS-TTR-LRx.

Eplontersen is a ligand-conjugated antisense investigational medicine currently in Phase III clinical trials for amyloid transthyretin cardiomyopathy (ATTR-CM) and amyloid transthyretin polyneuropathy (ATTR-PN).

It is designed to reduce the production of transthyretin (TTR protein) to treat both hereditary and non-hereditary forms of TTR amyloidosis (ATTR). The companies will jointly develop and commercialise eplontersen in the US, while AstraZeneca will develop and commercialise it in the rest of the world, except in Latin America.

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Eplontersen has the potential to halt the progression of TTR-mediated amyloidosis, irrespective of whether it’s caused by genetic mutations or aging. Thanks to its precise liver-targeting properties, it also has the potential to be a best-in-class treatment for patients suffering from this devastating disease and who currently have limited options.”

Hereditary ATTR-PN is expected to be the first indication for which the companies will seek regulatory approval for eplontersen, with the potential to file a new drug application with the FDA by the end of 2022.

AstraZeneca will pay Ionis an upfront payment of $200 million and additional conditional payments of up to $485 million following regulatory approvals. It will also pay up to $2.9 billion of sales-related milestones based on sales thresholds between $500 million and $6 billion, plus royalties in the range of low double-digit to mid-twenties percentage depending on the region. The collaboration includes territory-specific development, commercial and medical affairs cost-sharing provisions.