AstraZeneca Enters Agreement for Transthyretin Amyloidosis Medicine

 AstraZeneca recently entered into a global development and commercialization agreement with Ionis Pharmaceuticals for transthyretin amyloidosis medication, eplontersen.

Eplontersen is a ligand-conjugated antisense investigational medicine currently in Phase 3 clinical trials for amyloid transthyretin cardiomyopathy (ATTR-CM) and amyloid transthyretin polyneuropathy (ATTR-PN).

The drug is designed to reduce the production of transthyretin (TTR) protein to treat both hereditary and non-hereditary forms of TTR amyloidosis (ATTR).

AstraZeneca and Ionis Pharmaceuticals will jointly develop and commercialize eplontersen in the US, while AstraZeneca will develop and commercialize the drug in the rest of the world, except Latin America.

“Eplontersen has the potential to halt the progression of TTR-mediated amyloidosis, irrespective of whether it’s caused by genetic mutations or aging,” Mene Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said in the announcement.

“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,” Pangalos continued.

Under the terms of the conditions, AstraZeneca will pay Ionis Pharmaceuticals an upfront payment of $200 million and additional conditional payments of up to $485 million following regulatory approvals.

The company will also pay up to $2.9 billion of sales-related milestones based on sales thresholds between $500 million and $6 billion.

The transaction is expected to close in the fourth quarter of 2021, subject to customary closing conditions and regulatory clearances. 

ATTR-CM is a progressive condition that leads to progressive heart failure and death within four years from diagnosis. The disease is underdiagnosed and underestimated due to a lack of disease awareness and heterogeneity of symptoms, an AstraZeneca spokesperson said.

In May 2019, FDA approved Vyndaqel and Vyndamax capsules as the first treatment for ATTR-CM.

The agency granted the approval to FoldRx, a subsidiary of Pfizer. Although Vyndaqel and Vyndamax have the same active moiety, they are not substitutable on a milligram to milligram basis.

A Phase 3 clinical trial enrolled 441 patients to receive Vyndaqel or placebo. After an average of 30 months, the survival rate was higher in the Vyndaqel group than in the placebo group. The drug also reduced the number of hospitalizations for cardiovascular problems in patients as well.