Eplontersen reduced serum transthyretin by 70-85% across different genetic variants in patients with hereditary transthyretin amyloidosis with polyneuropathy, while maintaining neuropathy scores and improving quality of life compared to placebo.
- Eplontersen reduced serum TTR by 79.9% in early-onset Val30Met, 85.0% in late-onset Val30Met, and 70.6% in non-Val30Met patients
- Neuropathy impairment scores were maintained and quality of life improved with treatment versus worsening with placebo
- Benefits were consistent across different TTR genetic variants in this Phase 3 trial analysis
How this compares to prior research
Hereditary transthyretin amyloidosis with polyneuropathy presents differently depending on genetic variants, with Val30Met mutations showing variable age of onset and non-Val30Met variants having distinct clinical patterns. Previous treatments have shown variable efficacy across genetic subtypes, making it unclear whether therapies would work consistently for all variants. This study addresses whether eplontersen provides uniform benefits regardless of the underlying genetic mutation causing the disease.
Prevalence trends in amyloidosis-related conditions, global data, 1980–1989
Key findings
- Mean serum TTR reduction ranged from 70.6% to 85.0% with eplontersen versus placebo across early-onset Val30Met, late-onset Val30Met, and non-Val30Met genetic variant groups
- Modified Neuropathy Impairment Score+7 composite scores were generally well maintained from baseline to Week 66 with eplontersen across all genetic subgroups
- Norfolk Quality of Life-Diabetic Neuropathy total scores improved with eplontersen while worsening with placebo across all TTR variant subgroups
What this means in practice
- Ask your doctor about eplontersen if you have hereditary transthyretin amyloidosis, regardless of your specific genetic variant
- Expect potential stabilization of nerve function and quality of life improvements if starting this treatment
- Monitor your modified body mass index during treatment as it was maintained better than with placebo
Frequently asked questions
What is hereditary transthyretin amyloidosis with polyneuropathy?
It is a genetic disease where abnormal transthyretin protein builds up in nerves and organs, causing progressive nerve damage and disability. Different genetic variants affect disease onset and progression.
How does eplontersen work for this condition?
Eplontersen reduces the amount of transthyretin protein in the blood by 70-85%, which helps prevent further protein buildup and nerve damage across different genetic variants of the disease.
Did the treatment work equally well for all genetic variants?
Yes, the study found consistent benefits in reducing neuropathy impairment and improving quality of life across early-onset Val30Met, late-onset Val30Met, and non-Val30Met genetic variants.
Key terms explained
Transthyretin (TTR)
A protein made by the liver that transports thyroid hormone and vitamin A; abnormal forms cause amyloidosis
Val30Met variant
A specific genetic mutation in the TTR gene where valine is replaced by methionine at position 30
Neuropathy Impairment Score (mNIS+7)
A clinical scale measuring nerve damage severity including reflexes, sensation, and muscle strength
Source: Effect of Eplontersen in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy Across Genetic Variants: An Exploratory Analysis From the NEURO-TTRansform Trial. · DOI: doi: 10.1111/ene.70580