Ionis Pharmaceuticals has just announced that eplontersen met its coprimary endpoints in the phase 3 NEURO-TTRansform study, showing sustained transthyretin reduction and benefits in patients with polyneuropathy linked to hereditary transthyretin amyloidosis (hATTR) over 66 weeks.

The 66-week results revealed statistically significant and clinically meaningful changes from baseline in the modified Neuropathy Impairment Score +7 and the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy in patients given eplontersen when compared with an external placebo group.

Moreover, the study demonstrated a statistically significant reduction in serum transthyretin concentration, which was consistent with that reported at week 35. Safety and tolerability data were also consistent to that reported at week 35.

“The positive results from the 66-week analysis of the phase 3 NEURO-TTRansform trial show that eplontersen provided consistent and sustained transthyretin protein reduction and that a substantial number of patients improved in measures of both neuropathy progression and quality of life,” Sami Khella, MD, chief of the department of neurology at Penn Presbyterian Medical Center and professor of clinical neurology at University of Pennsylvania School of Medicine, said in a press release. “This builds on the favorable 35-week results, which first demonstrated eplontersen’s potential to significantly improve outcomes in this underserved population.”

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“These latest results from our NEURO-TTRansform study represent an important step towards delivering a potential new therapy for [hATTR polyneuropathy] patients living with this debilitating and fatal disease. We are encouraged by the sustained benefit demonstrated by eplontersen and what a self-administered treatment could mean for patients and families affected by [hATTR polyneuropathy],” Eugene Schneider, MD, executive vice president and chief clinical development officer of Ionis, said. “Together with our partner AstraZeneca, we look forward to sharing detailed results from this study at the upcoming American Academy of Neurology Annual Meeting.”

The presentation at the American Academy of Neurology Annual Meeting, taking place in April 2023, will include data from both the 35- and 66-week analyses.

“These results further underscore eplontersen’s potential to be a best-in-class treatment across all forms of transthyretin-mediated amyloidosis, including polyneuropathy and cardiomyopathy which can lead to heart failure,” Mene Pangalos, executive vice president of BioPharmaceuticals R&D at AstraZeneca, said. “With limited treatment options currently available, there is an urgent unmet medical need for new therapies and earlier, accurate diagnosis across the different types of this systemic, progressive, and fatal condition.”


Ionis reports positive topline 66-week results of eplontersen phase 3 study for patients with ATTRv-PN. News release. Ionis Pharmaceuticals, Inc.; March 27, 2023.