EFFICACY

WAINUA stopped polyneuropathy progression to preserve nerve function in adults with hATTR-PN*1-3

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WAINUA significantly halted the progression of polyneuropathy impairment vs external placebo at Week 35, with sustained reductions through Week 661-3

Assessed by the mNIS+7 composite score, which measured motor, sensory, and autonomic function1,3

  1. *As measured by mNIS+7 composite score, a validated score in hATTR-PN to quantify neurologic impairment and progression.1,3,5

  2. †The validated version of the mNIS+7 score used in the trial had a range of -22.3 to 346.3 points, with higher scores representing a greater severity of disease.1

  3. ‡Improvement is defined as a negative change from baseline; patients with missing data were counted as not improved.3

Responder analysis for mNIS+7 composite score at Week 35 and Week 661-3

Responder analysis at Week 351

mNIS+7 Responder Analysis mNIS+7 Responder Analysis

Patients treated with WAINUA had better mNIS+7 composite scores vs patients treated with placebo from baseline at Week 35 and Week 66.§2,3

  • Week 35: WAINUA, 49% vs placebo, 24%
  • Week 66 (post hoc analysis): WAINUA, 53% vs placebo, 19%

  1. Note: A responder (improvement) was defined as a patient whose mNIS+7 composite score change from baseline was less than threshold value of 0.2,3

  2. §At Week 35, the number of patients in each group of the full analysis set was used as the denominator (WAINUA, N=140; placebo, N=59).2,3

  3. At Week 66, the number of patients with nonmissing values in each group of the full analysis set was used as the denominator (WAINUA, N=128; placebo, N=52).2,3

Effect of WAINUA on polyneuropathy impairment through 3 years from treatment initiation6

NIS composite score is a component of the mNIS+7 composite score and measures muscle weakness, sensation, and reflexes. It does not include autonomic nervous system assessments (heart rate with deep breathing), nerve conduction studies (NCS), or quantitative sensory testing (QST).||5,6

NIS data from Week 162 interim analysis of NEURO-TTRansform extension study was measured from treatment initiation in the index study.6

MEAN (SEM) CHANGE FROM BASELINE IN NIS COMPOSITE SCORE6

Exploratory Endpoint Chart Exploratory Endpoint Chart

Note: The placebo group refers to the external placebo control arm from the NEURO-TTR trial. From Week 66 to Week 162, there was no external placebo group because the NEURO-TTR trial concluded at Week 66. No formal statistical analyses were performed.6,7

mNIS+7 was a co-primary endpoint in the NEURO-TTRansform index study, but only NIS, a component of the mNIS+7 composite score, was collected in the extension study. NIS data was extracted from mNIS+7 in NEURO-TTRansform (WAINUA) and NEURO-TTR (external placebo).1,6,7

The NEURO-TTRansform extension is an ongoing, Phase 3, open-label study evaluating the long-term efficacy and safety of WAINUA in patients who completed the NEURO-TTRansform index study. The interim analysis includes only patients randomized to receive WAINUA in the index study and excludes patients from the inotersen switch group. The demographics and clinical characteristics at baseline were generally similar between the index and extension cohorts. See study design.6

||NIS composite score is a component of the mNIS+7 composite score and is graded on a scale of 0 to 244, with higher scores representing greater severity of disease. Autonomic function is excluded from the components evaluated by NIS.5

WAINUA delivered significant and continuous improvements in quality of life in adults with hATTR-PN¶1-3

WAINUA significantly improved quality of life vs external placebo at Week 35, with sustained effect through Week 661-3

As measured by the Norfolk QoL-DN score, which measured domains including symptoms, daily activities, and physical function1

  1. As measured by Norfolk QoL-DN total score, a validated patient-reported quality-of-life assessment for patients with hATTR-PN.1,8,9

  2. #Improvement is defined as a negative change from baseline; patients with missing data were counted as not improved.3

  3. **The version of the Norfolk QoL-DN that was used in the trial had a range from -4 to 136 points, with higher scores representing greater impairment.1

  4. ††Norfolk QoL-DN was a key secondary endpoint at Week 35 and a co-primary endpoint at Week 66.1,3,4

Responder analysis for Norfolk QoL-DN total score at Week 35 and Week 661,3

Responder analysis at Week 351

Responder Analysis for Norfolk QoL-DN Responder Analysis for Norfolk QoL-DN

Patients treated with WAINUA had better Norfolk QoL-DN total scores vs patients treated with placebo from baseline at Week 35 and Week 66.‡‡2,3

  • Week 35: WAINUA, 56% vs placebo, 34%
  • Week 66 (post hoc analysis): WAINUA, 65% vs placebo, 23%

  1. Note: A responder (improvement) was defined as a patient whose Norfolk QoL-DN score change from baseline was less than threshold value of 0.2,3

  2. ‡‡At Week 35, the number of patients in each group of the full analysis set was used as the denominator (WAINUA, N=140; placebo, N=59).2,3

  3. At Week 66, the number of patients with nonmissing values in each group of the full analysis set was used as the denominator (WAINUA, N=128; placebo, N=52).2,3

Effect of WAINUA on quality of life through 3 years from treatment initiation6

Norfolk QoL-DN includes measures for physical functioning, symptoms score, and activities of daily living.1

Norfolk QoL-DN data from Week 162 interim analysis of NEURO-TTRansform extension study measured from treatment initiation in the index study6

MEAN (SEM) CHANGE FROM BASELINE IN NORFOLK QoL-DN TOTAL SCORE**6

Exploratory Endpoint Chart Exploratory Endpoint Chart

Note: The placebo group refers to the external placebo control arm from the NEURO-TTR trial. From Week 66 to Week 162, there was no external placebo group because the NEURO-TTR trial concluded at Week 66. No formal statistical analyses were performed.6,7

The NEURO-TTRansform extension is an ongoing, Phase 3, open-label study evaluating the long-term efficacy and safety of WAINUA in patients who completed the NEURO-TTRansform index study. The interim analysis includes only patients randomized to receive WAINUA in the index study and excludes patients from the inotersen switch group. The demographics and clinical characteristics at baseline were generally similar between the index and extension cohorts. See study design.6

See additional data on autonomic function for WAINUA

Additional data

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Explore the safety profile of WAINUA

WAINUA safety

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FOOTNOTES AND ABBREVIATIONS

EOT, end of treatment; hATTR-PN, polyneuropathy of hereditary transthyretin-mediated amyloidosis; LSM, least-squares mean; mNIS+7, modified Neuropathy Impairment Score +7; NIS, Neuropathy Impairment Score; Norfolk QoL-DN, Norfolk Quality of Life-Diabetic Neuropathy; QoL, quality of life; SEM, standard error of mean.

REFERENCES

  1. 1. WAINUA® (eplontersen) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2025.
  2. 2. Data on File, REF-205487, AZPLP.
  3. 3. Coelho T, Marques W Jr, Dasgupta NR, et al. Eplontersen for hereditary transthyretin amyloidosis with polyneuropathy [article and supplementary online content]. JAMA. 2023;330(15):1448-1458.
  4. 4. Coelho T, Ando Y, Benson MD, et al. 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;10(1):375-389.
  5. 5. Dyck PJB, González-Duarte A, Obici L, et al. Development of measures of polyneuropathy impairment in hATTR amyloidosis: From NIS to mNIS + 7. J Neurol Sci. 2019;405:116424.
  6. 6. Berk J, Coelho T, Conceição I, et al. Long-term efficacy and safety of eplontersen in patients with hereditary transthyretin amyloidosis with polyneuropathy: initial report from the open-label extension of the NEURO-TTRansform study. Presented at: 5th International ATTR Amyloidosis Meeting 2025; September 25-26, 2025; Baveno, Italy.
  7. 7. Data on File, REF-297876, AZPLP.
  8. 8. Vinik EJ, Hayes RP, Oglesby A, et al. The development and validation of the Norfolk QoL-DN, a new measure of patients’ perception of the effects of diabetes and diabetic neuropathy. Diabetes Technol Ther. 2005;7(3):497-508.
  9. 9. Vinik EJ, Vinik AI, Paulson JF, et al. Norfolk QoL-DN: validation of a patient reported outcome measure in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst. 2014;19(2):104-114.