Eplontersen is an investigational ligand-conjugated antisense (LICA) medicine, designed to treat all types of TTR amyloidosis (ATTR)


The Discovery Centre overhead view. (Credit: AstraZeneca.)

AstraZeneca has partnered with US-based biotech company Ionis Pharmaceuticals for the development and commercialisation of the latter’s eplontersen.

Eplontersen, previously called IONIS-TTR-LRX, is an investigational ligand-conjugated antisense (LICA) medicine, designed to treat TTR amyloidosis (ATTR).

The drug works by reducing the production of transthyretin (TTR protein), to treat all types of ATTR, a systemic, progressive and fatal disease.

Under the terms of the partnership agreement, the companies will jointly develop and commercialise the drug in the US, while AstraZeneca will develop and commercialise it in the remaining territories, excluding Latin America.

The British drugmaker will make a $200m upfront payment to Ionis, and additional conditional payments of up to $485m following regulatory approvals.

It will also make sales-related milestone payments of up to $2.9bn, based on sales thresholds between $500m and $6bn, in addition to royalties depending on the region.

The collaboration includes territory-specific development, commercial and medical affairs cost-sharing provisions.

Upon closing of the transaction, Ionis would continue to manufacture and supply eplontersen for the existing clinical trials and process qualification.

AstraZeneca will assume responsibility for commercial supply, book all sales generated, and the transaction is not expected to impact its financial guidance for 2021.

The company intends to fund the transaction using available cash on hand, and the acquisition is not expected to affect its core earnings for 2021.

It will be accounted for as an intangible asset acquisition, with potential future milestone payments to be capitalised into the intangible asset, said AstraZeneca.

ATTR causes cardiomyopathy and polyneuropathy, where TTR protein is misfolded in the cardiac myocardium and amassed as amyloid fibrils in peripheral nerves.

In ATTR patients, the TTR protein accumulates in the tissues of peripheral nerves, heart, eyes, kidneys, central nervous system, thyroid and bone marrow, which interferes with the normal functions of these tissues.

When the TTR protein fibrils enlarge, causing more damage to the tissues, resulting in worsening of the disease, poor quality of life and eventually death.