New Phase 3 Trial Data Show Eplontersen Improved Neuropathy in Over Half of Patients With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy


Study shows eplontersen maintains a consistent and sustained treatment effect and reinforces its potential treating hereditary transthyretin-mediated amyloid polyneuropathy, which can lead to heart failure.

Eplontersen (Eplontersen; AstraZeneca, Ionis Pharmaceuticals)—an investigational treatment for hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN)—improved neuropathy in 53% of patients who completed 66 weeks of therapy compared to baseline, according to results from the NEURO-TTRansform phase 3 trial presented in an Emerging Science Session at the American Academy of Neurology (AAN) 2023 Annual Meeting in Boston, Massachusetts.

Credit: Yurii Kibalnik -

Credit: Yurii Kibalnik -

ATTRv-PN causes peripheral nerve damage and motor disability within 5 years of diagnosis. The debilitating disease can be fatal without treatment.

“In the past, patients with hereditary transthyretin amyloid polyneuropathy usually deteriorated given the limited available treatments,” said primary investigator Sami Khella, MD, chief of the Department of Neurology at Penn Presbyterian Medical Center and Professor of Clinical Neurology at the Perelman School of Medicine at the University of Pennsylvania School of Medicine, in a press release. “[The] 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.”

In 2017, investigators at Ionis conducted the NEURO-TTR registrational trial, comparing the efficacy of inotersen (Tegsedi; Ionis Pharmaceuticals) and placebo. The global, open-label, and randomized NEURO-TTRansform trial evaluated the efficacy and safety of eplontersen in patients with ATTRv-PN, comparing the results to those from the 2017 placebo arm. Co-primary endpoints include serum transthyretin (TTR) concentration, neuropathy impairment, and quality of life (QoL).

At 66 weeks, 53% of patients on eplontersen who completed the study showed improvement in neuropathy compared to 19% of patients in the external treatment group. Overall, eplontersen improved neuropathy in 47% of patients compared to 17% in the placebo group. Disease progression, as measured by the modified Neuropathy Impairment Score +7 (mNIS+7), increased 0.28 and 25.06 points in the eplontersen and placebo group, respectively.

Using the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) to measure QoL, eplontersen was also shown to improve QoL by 5.5 points in 66 weeks; the placebo group experienced a 14.2-point change in worsened QoL. Generally, eplontersen improved QoL in more than 50% of patients whereas placebo improved QoL in 20%.

Adverse events (AEs) were comparable to the external placebo group across major categories, and the drug has a favorable safety and tolerability profile.

Eplontersen is an investigative ligand-conjugated antisense that reduces transthyretin (TTR protein) production to treat every type of the progressive and fatal ATTR disease. The FDA accepted AstraZeneca and Ionic’s new drug application for eplontersen, and they hope to receive regulatory approval soon.

“These results show that eplontersen sustains reduced transthyretin levels and improves neuropathy progression and quality of life consistently across a substantial number of patients,” said Mene Pangalos, executive vice president, BioPharmaceuticals R&D, AstraZeneca, in the press release. “We are confident in eplontersen’s potential to be a much needed and differentiated treatment option for patients living with all types of this devastating disease, which can also lead to heart failure.”


AstraZeneca. NEURO-TTRansform Phase III results presented at AAN showed eplontersen demonstrated consistent and sustained improvement in all measures of disease and quality of life through 66 weeks. News Release. April 24, 2023. Accessed on April 25, 2023.

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