Wainua Treatment for hATTR-PN Associated with Improved Neuropathy Impairment and Quality of Life According to Long-Term Data

People with hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN) who were treated with Wainua (eplontersen; Astra Zeneca, Cambridge, UK; Ionis Pharmaceuticals, Carlsbad, CA) for 15 months showed improvements in quality of life (QoL) and neuropathy impairment, compared to historical placebo. Results of multiple subgroup analyses of the phase 3 NEURO-TTRansform study (NCT04136184) were presented at the 2024 International Symposium of Amyloidosis (ISA). Additional subgroup analyses revealed that the improvements associated with Wainua were consistent regardless of participant sex and that disease progression was slower for Wainua-treated participants with the Val30Met mutation of the transthyretin (TTR) gene.

Key presentations, as highlighted in a press release from Ionis Pharmaceuticals and AstraZeneca, include:

• Neuropathy Impairment and Nutritional Status with Eplontersen in Patients with Hereditary TransthyretinMediated Amyloidosis – Abstract 174, presented by Dr. Jonas Wixner, Umeå University
• Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy: An Exploratory Analysis in Patients with the V30M TTR Variant and EarlyOnset or Late-Onset disease – Abstract 230, presented by Dr. Julian D. Gillmore, University College London
• Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy: An Exploratory Analysis of Treatment Effect in Male and Female Patients – Abstract 202 presented by Dr. Márcia WaddingtonCruz, Federal University of Rio de Janeiro

Notable findings from these studies are as follows:

• People treated with Wainua trended towards improvement in modified body mass index (mBMI), while those treated with placebo trended toward worsening in this outcome.
• Wainua treatment was associated with consistent benefit in the following outcomes: modified Neuropathy Impairment Score +7 (mNIS +7) and Norfolk QoLDiabetic Neuropathy (Norfolk QoL-DN) total score.
• Mean change in mNIS +7 composite score and Norfolk QoLDN total score from baseline to week 66 were improved for both male and female individuals who were treated with Wainua relative to those treated with placebo.

NEURO-TTRansform was a global, open-label, randomized study evauating the efficacy and safety of Wainua in 168 participants aged 18 to 82 years with a diagnosis of hATTR-PN. Treatment with Wainua was associated with reduced serum concentrations of TTR and improvements in neuropathy impairment and QoL. The FDA approval of Wainua in 2023 was based on the results of the Neuro-TTRansform clinical trial.