Efficacy of Eplontersen According to Baseline Polyneuropathy Severity in Patients with Hereditary Transthyretin Amyloidosis: A Subgroup Analysis of the NEURO-TTRansform Index Study
Thomas Brannagan1, John Berk2, Morie Gertz3, Sami Khella4, Ahmad Masri5, Mathew Maurer6, Marcia Waddington Cruz7, Theodore Kwoh8, Maksym Pola9, Jonatan Nåtman9, Laura Piera Obici10
1Department of Neurology, Columbia University, Vagelos College of Physicians and Surgeons, 2Boston University School of Medicine, 3Mayo Clinic, 4University of Pennsylvania School of Medicine, 5Oregon Health & Science University, 6Columbia University Irving Medical Center, 7CEPARM, Amyloidosis Center, University Hospital, Federal University of Rio de Janeiro, 8Ionis Pharmaceuticals, Inc., 9AstraZeneca, 10IRCCS Fondazione Policlinico San Matteo
Objective:
To assess the impact of baseline polyneuropathy severity on eplontersen response, in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).
Background:
Patients with ATTRv amyloidosis experience motor, sensory, and autonomic neuropathies that impact quality of life (QoL). In NEURO-TTRansform (NCT04136184), eplontersen demonstrated benefits in QoL and neuropathy to Week 65/66 versus historical placebo in patients with ATTRv-PN.
Design/Methods:
NEURO-TTRansform participants (N=141) and participants who received historical placebo (N=59) were divided post hoc into quartiles based on baseline Neuropathy Impairment Score (NIS; 3.5–<21.5 [Q1; least impairment at baseline]; 21.5–<39.5 [Q2]; 39.5–<62.5 [Q3]; 62.5–<127.8 [Q4; most impairment at baseline]). Neuropathic impairment (modified NIS+7 [mNIS+7]) and QoL (Norfolk Quality of Life-Diabetic Neuropathy [Norfolk QoL-DN] questionnaire) were assessed.
Results:
Mean (SD) age was lowest in Q1 and highest in Q4 (placebo 52.1 [14.9]–64.6 [13.3] years; eplontersen 48.2 [15.8]–58.8 [14.1] years). Mean (SD) baseline mNIS+7 scores ranged from 28.8 (13.1)–123.2 (16.7) (placebo) and 31.7 (11.5)–132.7 (30.2) (eplontersen). Across quartiles, mean (SE) mNIS+7 scores increased numerically (worsened) from baseline to Week 66 for placebo (change from baseline: Q1, 13.8 [5.7]; Q2, 17.0 [7.1]; Q3, 41.9 [7.5]; Q4, 25.2 [4.7]), but remained stable for eplontersen (Q1, 0.4 [2.1]; Q2, −4.7 [3.6]; Q3, 2.2 [3.5]; Q4, 0.9 [3.2]). Mean (SD) baseline Norfolk QoL-DN scores ranged from 31.5 (25.6)–64.9 (20.9) (placebo) and 21.6 (19.9)–61.9 (24.7) (eplontersen). Mean (SE) scores increased numerically (worsened) to Week 66 for placebo (change from baseline: Q1, 7.2 [4.9]; Q2, 1.0 [6.7]; Q3, 27.0 [4.9]; Q4, 10.8 [4.6]), but improved for eplontersen (Q1, −5.9 [2.2]; Q2, −9.0 [3.7]; Q3, −9.0 [4.1]; Q4, −5.0 [2.8]).
Conclusions:
Consistent benefits of eplontersen treatment in the degree of neuropathy impairment and in QoL were observed to Week 66, regardless of baseline PN severity.
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