Eplontersen met co-primary and secondary endpoints in interim analysis of the NEURO-TTRansform phase III trial for hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN).

In the trial, eplontersen reached a statistically significant and clinically meaningful change from baseline for its co-primary endpoint of percent change in serum transthyretin (TTR) concentration, reducing TTR protein production. Eplontersen also reached its co-primary endpoint of change from baseline in the modified Neuropathy Impairment Score +7 (mNIS+7), a measure of neuropathic disease progression1, versus external placebo group.

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

ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without treatment, is generally fatal within a decade.

Eplontersen, formerly known as IONIS-TTR-LRx, is a ligand-conjugated antisense (LICA) investigational medicine designed to reduce the production of TTR protein at its source to treat both hereditary and non-hereditary forms of ATTR2.

Based on the 35-week interim trial results, the companies will seek regulatory approval for eplontersen and plan to file a new drug application with the FDA in 2022. ATTRv-PN is expected to be the first indication for which AstraZeneca and Ionis will seek regulatory approval for eplontersen. The results from the 35-week interim analysis of the trial will be submitted for presentation at a forthcoming medical meeting. As part of a global development and commercialisation agreement with Ionis, eplontersen will be jointly developed and commercialised by both companies in the US and will be developed and commercialised in the rest of the world by AstraZeneca (with the exception of Latin America).

Eplontersen was granted Orphan Drug Designation in the US and is also currently being evaluated in the CARDIO-TTRansform Phase III trial for amyloid transthyretin cardiomyopathy (ATTR-CM), a systemic, progressive and fatal condition that leads to progressive heart failure and death within four years from diagnosis.