AstraZeneca and Ionis Announce $3.5 Billion Collaboration to Develop and Commercialize Eplontersen, an Investigational Antisense Oligonucleotide Therapy for ATTR Amyloidosis

On December 7, AstraZeneca and Ionis Pharmaceuticals (hereinafter referred to as "Ionis") announced a global development and commercialization agreement worth over $3.5 billion for the latter's investigational antisense oligonucleotide (ASO) eplontersen (IONIS-TTR-LRX). According to the terms of the agreement, AstraZeneca will pay Ionis an upfront payment of $200 million and up to $485 million in additional conditional payments. In addition, based on sales thresholds ranging from $500 million to $6 billion, AstraZeneca will also pay up to $2.9 billion in sales-related milestone payments.

Under the terms of the agreement, the two parties will jointly develop and commercialize eplontersen in the United States, and AstraZeneca will obtain the rights to develop and commercialize eplontersen in regions other than Latin America. Ionis will continue to manufacture and supply eplontersen for existing clinical studies and process research. AstraZeneca will be responsible for commercial supply, with the transition timeline to be agreed upon by both parties. The transaction is expected to be completed in the fourth quarter of 2021. Eplontersen is the fifth drug developed in collaboration between Ionis and AstraZeneca. Previously, Ionis and AstraZeneca were also researching potential treatments for kidney disease, cardiovascular disease, and cancer.

Amyloid Transthyretin Cardiomyopathy (ATTR-CM) is a systemic, progressive, and fatal disease that can lead to progressive heart failure and death within 4 years after diagnosis. Hereditary Amyloid Transthyretin Polyneuropathy (ATTR-PN) is a debilitating disease that causes peripheral nerve damage with motor disability within 5 years of diagnosis and is generally fatal within 10 years if left untreated. The cardiomyopathy and polyneuropathy caused by ATTR result from the misfolding of TTR protein due to aging or genetic mutations, leading to accumulation as amyloid fibrils in the myocardium and peripheral nerves, respectively. TTR protein is primarily produced in the liver and normally serves as a carrier for vitamin A. In ATTR patients, both mutant and wild-type TTR proteins accumulate in tissues in fibrillar form, causing intractable peripheral sensory-motor neuropathy, autonomic neuropathy, and/or cardiomyopathy, along with other disease manifestations. Globally, it is estimated that there are 300,000 to 500,000 patients with ATTR-CM and 10,000 to 40,000 patients with ATTR-PN.

Eplontersen is an investigational ligand-conjugated antisense oligonucleotide therapy designed to reduce the production of transthyretin (TTR) protein for the treatment of all types of transthyretin-mediated amyloidosis (ATTR). The drug is currently in Phase 3 clinical trials for the treatment of ATTR-CM and ATTR-PN. According to the press release, hereditary ATTR-PN is expected to be the first indication for which eplontersen will seek regulatory approval, with a New Drug Application potentially being submitted to the U.S. FDA by the end of 2022.

References:

[1] AstraZeneca and Ionis sign deal to develop and commercialise eplontersen. Retrieved 2021-12-07, from https://www.astrazeneca.com/media-centre/press-releases/2021/astrazeneca-ionis-to-collaborate-on-eplontersen.html

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