NEURO-TTRansform
Trial question
What is the role of eplontersen in patients with hereditary transthyretin amyloidosis with polyneuropathy?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
31.0% female
69.0% male
N = 204
204 patients (63 female, 141 male).
Inclusion criteria: adults with Coutinho stage 1 or 2 hereditary transthyretin amyloidosis with polyneuropathy, Neuropathy Impairment Score 10-130, and a documented transthyretin variant.
Key exclusion criteria: low retinol level at screening; Karnofsky performance status ≤ 50; poor renal function; known T1DM or T2DM; other causes of sensorimotor or autonomic neuropathy; anticipated survival < 2 years.
Interventions
N=144 eplontersen (at a subcutaneous dose of 45 mg every 4 weeks).
N=60 placebo (subcutaneous placebo weekly).
Primary outcome
Mean reduction in serum transthyretin concentration at week 65
81.7%
11.2%
81.7 %
61.3 %
40.9 %
20.4 %
0.0 %
Eplontersen
Placebo
Significant
increase ▲
NNT = 1
Significantly greater reduction in mean serum transthyretin concentration at week 65 (81.7% vs. 11.2%; ARD 70.4, 95% CI 65.7 to 75.2).
Secondary outcomes
Significant decrease in mean change of modified Neuropathy Impairment Score +7 composite score at week 66 (0.3 points vs. 25.1 points; AD -24.8 points, 95% CI 18.6 to 31).
Significant decrease in mean change of Norfolk QoL Questionnaire-Diabetic Neuropathy total score at week 66 (-5.5 points vs. 14.2 points; AD -19.7 points, 95% CI -25.6 to -13.8).
Significant decrease in mean change of Neuropathy Symptom and Change score at week 66 (-0.03 points vs. 8.2 points; AD -8.2 points, 95% CI -10.7 to -5.8).
Safety outcomes
No significant difference in treatment-emergent adverse events.
Conclusion
In adults with Coutinho stage 1 or 2 hereditary transthyretin amyloidosis with polyneuropathy, Neuropathy Impairment Score 10-130, and a documented transthyretin variant, eplontersen was superior to placebo with respect to mean reduction in serum transthyretin concentration at week 65.
Reference
Teresa Coelho, Wilson Marques Jr, Noel R Dasgupta et al. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA. 2023 Oct 17;330(15):1448-1458.
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