Phase III Study of AstraZeneca's Innovative Therapy was Successful! A Listing Application Will be Submitted

On June 21, AstraZeneca announced that the Phase III NEURO-TTRansform study of eplontersen in hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) met co-primary endpoints at the interim analysis and secondary endpoint.

Eplontersen (IONIS-TTR-LRx), is an investigational ligand-conjugated antisense (LICA) drug designed to reduce serum transthyretin (TTR) production for the treatment of hereditary and non-hereditary ATTR.

Results of the 35-week interim analysis showed a statistically significant and clinically meaningful change in eplontersen's serum TTR concentration from baseline in percent change and a significant reduction in TTR protein production, meeting the primary endpoint. Compared with the external placebo arm, eplontersen also had a significant change from baseline in Modified Neuropathy Impairment Score+7 (mNIS+7), meeting the co-primary endpoint. mNIS+7 is a measure of neuropathy progression.

High-level results showed that the trial also met a secondary endpoint: change from baseline in the Norfolk Quality of Life Questionnaire- Diabetic Neuropathy (Norfolk QoL-DN), showing that eplontersen significantly improved patient-reported life compared to the external placebo group quality. In the trial, eplontersen demonstrated a favorable safety and tolerability profile with no specific safety concerns.

Based on the findings, AstraZeneca and Ionis will seek regulatory approval for eplontersen and plan to submit a New Drug Application to the U.S. FDA in 2022. ATTRv-PN is expected to be the first approved indication for eplontersen.

Under the global development and commercialization agreement between AstraZeneca and Ionis, the two companies will jointly develop and commercialize eplontersen in the United States, while development and commercialization in the rest of the world (excluding Latin America) will be completed by AstraZeneca.

Eplontersen has been granted orphan drug designation by the U.S. FDA and is currently undergoing a Phase III CARDIO-TTRansform trial to evaluate the efficacy of eplontersen in the treatment of amyloid-transthyretin cardiomyopathy (ATTR-CM).

ATTR cardiomyopathy and polyneuropathy are progressive systemic diseases caused by aging or genetic mutation in which TTR protein misfolds and accumulates as amyloid fibrils in the heart muscle and peripheral nerves, the presence of TTR fibrils can interfere with these tissues normal function. ATTRv-PN can cause peripheral nerve damage with movement impairment within five years of diagnosis and is often fatal within ten years if left untreated. Worldwide, approximately 40,000 patients have ATTRv-PN.