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PubMed · 42697856

Impact of Baseline Polyneuropathy Severity on Eplontersen Efficacy in the NEURO-TTRansform Clinical Trial.

Thomas H Brannagan·Markus Weiler·Márcia Waddington Cruz·Sami Khella·John L Berk·Morie Gertz·Ahmad Masri·Mathew S Maurer·Jonas Wixner·Jonatan Nåtman·T Jesse Kwoh·Maksym Pola·Laura Obici
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Abstract

BACKGROUND AND AIMS: In the NEURO-TTRansform clinical trial (NCT04136184), eplontersen improved neuropathy impairment and quality of life (QoL) through Week 66 versus the NEURO-TTR historical placebo in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This analysis assessed the impact of baseline ATTRv-PN severity on eplontersen response in patients from NEURO-TTRansform. METHODS: This post hoc analysis grouped patients into tertiles by baseline Neuropathy Impairment Score (NIS): T1 (least baseline impairment: 3.5 to <&#x2009;27.5; n&#x2009;=&#x2009;67), T2 (27.5 to <&#x2009;55.0; n&#x2009;=&#x2009;67), and T3 (55.0 to <&#x2009;127.8; n&#x2009;=&#x2009;66). Outcomes assessed were neuropathy impairment (modified NIS+7 [mNIS+7] and NIS, Neuropathy Symptom and Change, Polyneuropathy Disability), QoL (Norfolk QoL-Diabetic Neuropathy), physical functioning (36-Item Short-Form Health Survey Physical Component Summary), nutritional status (modified body mass index), and serum transthyretin levels; these were compared with NEURO-TTR historical placebo. Autonomic dysfunction (Composite Autonomic Symptom Score-31), disability (Rasch-built Overall Disability Scale), and walking speed (10-Meter Walk Test) were also assessed. Final assessments were carried out following 65/66 or 81/85&#x2009;weeks of treatment. RESULTS: Mean mNIS+7 composite scores were maintained over 85&#x2009;weeks with eplontersen (changes from baseline of -4.5 [T1], -1.3 [T2], and -2.6 [T3] points). Other disease parameter scores were similarly maintained or improved with eplontersen. Patients receiving placebo experienced disease worsening across outcomes. T1 mean disease scores were typically better than in T2 and T3. INTERPRETATION: Consistent, sustained benefits of eplontersen were observed regardless of baseline ATTRv-PN severity. These findings strengthen the importance of early treatment initiation for patients with ATTRv-PN across the disease spectrum.

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HumansAmyloid Neuropathies, FamilialFemaleMalePolyneuropathiesSeverity of Illness IndexMiddle AgedQuality of LifeAgedOutcome Assessment, Health CareDouble-Blind MethodOligonucleotidesATTRv&#x2010;PNTTR gene silencereplontersenhereditary transthyretin amyloidosispolyneuropathyJournal ArticleRandomized Controlled Trial

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Thomas H Brannagan, Markus Weiler, M&#xe1;rcia Waddington Cruz, Sami Khella, John L Berk, Morie Gertz, Ahmad Masri, Mathew S Maurer, Jonas Wixner, Jonatan N&#xe5;tman, T Jesse Kwoh, Maksym Pola, Laura Obici. 2026. Impact of Baseline Polyneuropathy Severity on Eplontersen Efficacy in the NEURO-TTRansform Clinical Trial.. https://doi.org/10.1111/jns.70167

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Journal Article; Randomized Controlled Trial resourceAged subjectDouble-Blind Method subjectFemale subjectHumans subjectJournal Article subjectMale subjectMiddle Aged subjectOutcome Assessment, Health Care subjectPolyneuropathies subjectRandomized controlled trials studypolyneuropathy subject

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