NEURO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
Summary
The main objective of this study was to evaluate the efficacy of eplontersen as compared with the historical control of the placebo cohort in the NEURO-TTR trial (NCT01737398/2012-001831-30), in subjects with hereditary transthyretin-mediated amyloidosis polyneuropathy (hATTR-PN). For more information, please visit http://www.neuro-ttransform.com/.
Timeline
- Start
- 2019-12-11
- Primary completion
- 2023-04-11
- Completion
- 2023-07-12
Outcome
Met primary endpoint
registry analysis (superiority test); Eplontersen vs External Placebo; p = 0.00000001; Difference in LS Mean -24.7593 (95% CI -30.9552 to -18.5635); MMRM NCT04136184 ↗
registry analysis (superiority test); Eplontersen vs External Placebo; p = 0.00000001; Difference in LS Mean -19.7352 (95% CI -25.6301 to -13.8403); MMRM NCT04136184 ↗
registry analysis (superiority test); Eplontersen vs External Placebo; p = 0.00000001; Difference in LS Mean -70.42 (95% CI -75.17 to -65.66); MMRM NCT04136184 ↗
registry analysis (superiority test); Eplontersen vs External Placebo; p = 0.00000001; Difference in LS Mean -66.65 (95% CI -71.59 to -61.71); MMRM NCT04136184 ↗
registry analysis (superiority test); Eplontersen vs External Placebo; p = 0.00012203; Difference in LS Mean -9.3542 (95% CI -13.8691 to -4.8394); MMRM NCT04136184 ↗
release “NEURO-TTRansform study met all co-primary and secondary endpoints” ionis.com ↗
release “Detailed results from the NEURO-TTRansform Phase III trial in patients with hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) showed AstraZeneca and Ionis’ eplontersen met all co-primary endpoints” astrazeneca.com ↗
Publications
- Results Coelho T, Marques W Jr, Dasgupta NR, Chao CC, Parman Y, Franca MC Jr, Guo YC, Wixner J, Ro LS, Calandra CR, Kowacs PA, Berk JL, Obici L, Barroso FA, Weiler M, Conceicao I, Jung SW, Buchele G, Brambatti M, Chen J, Hughes SG, Schneider E, Viney NJ, Masri A, Gertz MR, Ando Y, Gillmore JD, Khella S, Dyck PJB, Waddington Cruz M; NEURO-TTRansform Investigators. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA. 2023 Oct 17;330(15):1448-1458. doi: 10.1001/jama.2023.18688.
- Waddington Cruz M, Berk JL, Parman Y, Gertz M, Khella S, Weiler M, Kwoh TJ, Pola M, Reicher B, Natman J, Dasgupta NR, Wixner J. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy: An Exploratory Analysis of Treatment Effect in Male and Female Patients. Muscle Nerve. 2026 Jun;73(6):1118-1127. doi: 10.1002/mus.70230. Epub 2026 Apr 6.
- Gillmore JD, Adams D, Weiler M, Masri A, Obici L, Natman J, Kwoh TJ, Reicher B, Revkin J, Cruz MW, Gertz M, Chao CC. Effect of Eplontersen in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy Across Genetic Variants: An Exploratory Analysis From the NEURO-TTRansform Trial. Eur J Neurol. 2026 Apr;33(4):e70580. doi: 10.1111/ene.70580.
- Masri A, Maurer MS, Claggett BL, Kulac I, Waddington Cruz M, Conceicao I, Weiler M, Berk JL, Gertz M, Gillmore JD, Rush S, Chen J, Zhou W, Kwoh J, Duran JM, Tsimikas S, Solomon SD. Effect of Eplontersen on Cardiac Structure and Function in Patients With Hereditary Transthyretin Amyloidosis. J Card Fail. 2024 Aug;30(8):973-980. doi: 10.1016/j.cardfail.2023.11.016. Epub 2023 Dec 7.
- Coelho T, Waddington Cruz M, Chao CC, Parman Y, Wixner J, Weiler M, Barroso FA, Dasgupta NR, Jung SW, Schneider E, Viney NJ, Dyck PJB, Ando Y, Gillmore JD, Khella S, Gertz MA, Obici L, Berk JL. Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen. Neurol Ther. 2023 Feb;12(1):267-287. doi: 10.1007/s40120-022-00414-z. Epub 2022 Dec 16.
- Coelho T, Ando Y, Benson MD, Berk JL, Waddington-Cruz M, Dyck PJ, Gillmore JD, Khella SL, Litchy WJ, Obici L, Monteiro C, Tai LJ, Viney NJ, Buchele G, Brambatti M, Jung SW, St L O'Dea L, Tsimikas S, Schneider E, Geary RS, Monia BP, Gertz M. Design and Rationale of the Global Phase 3 NEURO-TTRansform Study of Antisense Oligonucleotide AKCEA-TTR-LRx (ION-682884-CS3) in Hereditary Transthyretin-Mediated Amyloid Polyneuropathy. Neurol Ther. 2021 Jun;10(1):375-389. doi: 10.1007/s40120-021-00235-6. Epub 2021 Feb 26.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Eplontersen | Antisense oligonucleotide | 45 mg | Subcutaneous |
| Comparator | Inotersen | Antisense oligonucleotide | 300 mg | Subcutaneous |