Eplontersen Meets Endpoints in Hereditary Transthyretin-Mediated Amyloid Polyneuropathy

Eplontersen is an investigational ligand-conjugated antisense medicine designed to reduce the production of TTR protein to treat both hereditary and nonhereditary forms of ATTR.

Topline results were announced from a phase 3 study evaluating eplontersen in patients with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN).

Hereditary ATTR is a severe, progressive and life-threatening disease caused by the abnormal formation and aggregations of transthyretin (TTR) amyloid deposits in various tissues and organs. Eplontersen is an investigational ligand-conjugated antisense medicine designed to reduce the production of TTR protein. 

The global, multicenter, open-label, randomized NEURO-TTRansform study (ClinicalTrials.gov Identifier: NCT04136184) included adults with a diagnosis of hereditary ATTRv-PN with stage 1 or 2 polyneuropathy. The study compared the efficacy and safety of eplontersen, administered via subcutaneous injection once every 4 weeks, to the historical placebo arm from the Tegsedi® (inotersen) NEURO-TTR trial (ClinicalTrials.gov Identifier: NCT01737398).

A 35-week interim analysis showed that treatment with eplontersen resulted in a statistically significant and clinically meaningful change from baseline in the percent change in serum TTR concentration and the modified Neuropathy Impairment Score +7 (a measure of neuropathic disease progression), compared with the historical placebo arm (both primary endpoints).

Significant improvement in patient-reported quality of life (assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy) was also observed in the eplontersen arm when compared with placebo. The safety profile of eplontersen was found to be favorable and consistent with that observed across other clinical programs. “We are pleased that the data in the NEURO-TTRansform study demonstrate eplontersen had a positive impact on disease progression, including improvement in neuropathy impairment and quality of life in a substantial number of patients,” said Eugene Schneider, MD, Ionis’ executive vice president and chief clinical development officer. “These highly statistically significant and clinically meaningful results put us on the cusp of providing a new therapeutic option for polyneuropathy patients living with this debilitating and fatal disease.”

The FDA previously granted Orphan Drug designation to eplontersen for the treatment of patients with ATTR. The Company plans to file a New Drug Application with the Food and Drug Administration (FDA) this year.

Eplontersen is also being evaluated in the phase 3 CARDIO-TTRansform study (ClinicalTrials.gov Identifier: NCT04136171) for amyloid transthyretin cardiomyopathy.


Ionis announces eplontersen met co-primary and secondary endpoints in interim analysis of the phase 3 NEURO-TTRansform study for hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN). News release. Ionis Pharmaceuticals, Inc. Accessed June 21, 2022. https://www.prnewswire.com/news-releases/ionis-announces-eplontersen-met-co-primary-and-secondary-endpoints-in-interim-analysis-of-the-phase-3-neuro-ttransform-study-for-hereditary-transthyretin-mediated-amyloid-polyneuropathy-attrv-pn-301571475.html

This article originally appeared on MPR