Eplontersen, an investigational ligand-conjugated antisense medicine designed to inhibit the production of the transthyretin (TTR) protein, met all coprimary and secondary endpoints at 66 weeks in the phase 3 NEURO-TTRansform study in patients with hereditary transthyretin amyloidosis (hATTR) with polyneuropathy (PN).

“In the past, patients with hereditary transthyretin amyloid polyneuropathy usually deteriorated given the limited available treatments. This new study shows eplontersen can halt progression of neuropathy and improve quality of life at 66 weeks when compared to placebo,” Sami Khella, MD, principal investigator on the NEURO-TTRansform study, explained in a press release.

“Today’s important results demonstrate that eplontersen has a consistent and sustained treatment effect and reinforces its potential as an important medicine for the thousands of patients living with this debilitating and fatal disease.”

Almost half (47%) of patients treated with eplontersen showed improvements in neuropathy at 66 weeks compared with baseline versus 17% in the external placebo group. The proportion increased to 53% for study completers versus 19% in the external placebo group.

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Moreover, patients treated with eplontersen demonstrated consistent and sustained reduction in serum TTR concentration, as well as improvements in quality of life at 66 weeks.

Eplontersen also achieved statistically significant improvements in all secondary endpoints compared with the external placebo group and continued to demonstrate a favorable safety and tolerability profile.

Eugene Schneider, MD, executive vice president and chief clinical development officer at Ionis, was also optimistic about the results. “In the NEURO-TTRansform study, we were encouraged to see a substantial number of patients treated with eplontersen improved in measures of neuropathy impairment and quality of life at both the interim and final analyses.”

“We and our partners at AstraZeneca are especially grateful to the patients who participated in this study. With our potential approval in the US in December and plans to file for regulatory approval in the EU and other countries, we are looking forward to potentially bringing eplontersen to ATTRv-PN patients in this largely underrecognized global patient population,” he added.

Eplontersen was granted Orphan Drug Designation by the US Food and Drug Administration and is currently being evaluated in the phase 3 CARDIO-TTRansform study for hATTR with cardiomyopathy (ATTR-CM).


Eplontersen halted ATTRv-PN disease progression and improved neuropathy impairment and quality of life in phase 3 study through 66 weeks. News release. Ionis Pharmaceuticals, Inc.; April 24, 2023.