AKCEA-TTR-LRx (ION-682884)

AKCEA-TTR-LRx (ION-682884) is an RNA-targeted therapy being co-developed by Ionis Pharmaceuticals and Akcea Therapeutics for the treatment of adults with familial amyloid polyneuropathy (FAP), also known as hereditary transthyretin amyloidosis (hATTR). AKCEA-TTR-LRx is being developed for all forms of transthyretin amyloidosis (ATTR) including FAP and wild-type (ATTRwt).

How does AKCEA-TTR-LRx work?

In ATTR amyloidosis, mutations in the TTR gene lead to the abnormal folding and accumulation of a protein called transthyretin (TTR) in the cells and tissues of the body, particularly in the nervous system and the heart. These  deposits of TTR protein lead to progressive organ failure.

AKCEA-TTR-LRx is a second-generation RNA-targeted therapy built on Ionis’s ligand conjugated antisense (LICA) technology platform, which allows for enhanced uptake (absorption) and specific targeting of tissues. AKCEA-TTR-LRx prevents the translation of TTR RNA into protein. (RNA serves as the template molecule for protein production from genes). This should prevent the production of TTR protein and its accumulation inside cells.

AKCEA-TTR-LRx in clinical trials

A Phase 1/2 clinical trial (NCT03728634) is evaluating the safety and effectiveness of single and multiple doses of AKCEA-TTR-LRx in a group of 47 participants that includes healthy volunteers and FAP patients.

Preliminary results from the Phase 1 part of the trial showed that AKCEA-TTR-LRx is well-tolerated and could reduce accumulated TTR protein levels in healthy volunteers by as much as 94% after 13 weeks when administered at a dose of 90 mg per month. The study is expected to be completed in August.

A Phase 3 clinical trial (NCT04136184) called NEURO-TTRansform is currently recruiting an estimated 140 FAP patients in the U.S. to study the safety and effectiveness of AKCEA-TTR-LRx. Patients will receive the treatment once every four weeks for 65 weeks.

The results of the trial will be compared to those of a Phase 2/3 clinical trial (NCT01737398) of Tegsedi (inotersen), a U.S. Food and Drug Administration (FDA)-approved therapy for FAP. Patients who are already on Tegsedi will be transferred to AKCEA-TTR-LRx therapy after a period of 35 weeks. The trial is expected to be completed in January 2024.

A Phase 3 clinical trial (NCT04136171), called CARDIO-TTRansform is poised to recruit an estimated 750 participants in the U.S. to evaluate the effectiveness of AKCEA-TTR-LRx compared to placebo in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The study is expected to be completed in June 2024.


Last updated: Jan. 28, 2020


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