Last updated Feb. 3, 2022, by Teresa Carvalho, MS
 Fact-checked by Joana Carvalho, PhD
Eplontersen, formerly known as AKCEA-TTR-LRx and ION-682884, is an RNA-targeted therapy being co-developed by Ionis Pharmaceuticals and AstraZeneca for all forms of transthyretin amyloidosis (ATTR), including familial amyloid polyneuropathy (FAP).
How does eplontersen work?
In FAP, mutations in the TTR gene lead to the abnormal folding and accumulation of a protein called transthyretin (TTR) in cells and tissues of the body, particularly in the nervous system and the heart. These TTR deposits lead to progressive organ failure.
Eplontersen is a second-generation RNA-targeted therapy built on Ionis’ ligand conjugated antisense technology platform. It’s designed to reduce the production of the TTR protein — potentially preventing the buildup of toxic clumps — by stopping the translation of TTR RNA into protein. RNA is an intermediary molecule that serves as a template for the production of proteins.
Eplontersen in clinical trials
A Phase 1/2 trial (NCT03728634) evaluated the safety and effectiveness of single and multiple doses of eplontersen in a group of 47 participants, including healthy volunteers and FAP patients.
Preliminary results from the Phase 1 part of the trial showed that eplontersen was well-tolerated and could reduce TTR protein levels in healthy volunteers by as much as 94% after 13 weeks when administered at a dose of 90 mg per month.
An ongoing Phase 3 trial (NCT04136184), called NEURO-TTRansform, enrolled 168 FAP patients to study the safety and effectiveness of eplontersen. Patients are receiving the treatment once every four weeks for 65 weeks.
Results from this trial will be compared to those of a Phase 2/3 trial (NCT01737398) of Tegsedi (inotersen), an FDA-approved therapy for FAP. Patients who are already on Tegsedi will be transferred to eplontersen after a period of 35 weeks. The trial is expected to be completed in January 2024.
A Phase 3 trial (NCT04136171), called CARDIO-TTRansform, will include around 750 participants to evaluate the effectiveness of eplontersen compared to placebo in patients with transthyretin-mediated amyloid cardiomyopathy, a condition wherein TTR deposits accumulate mainly in the heart. The study is expected to be completed in June 2024.
Other details
The FDA has granted orphan drug designation to eplontersen for ATTR amyloidosis. Therapies given this designation are entitled to several benefits and incentives, including seven years of market exclusivity upon approval, credits for clinical testing, and exemption from FDA application fees.
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