Switching from inotersen to eplontersen in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: analysis from NEURO-TTRansform.
Journal
Journal of Neurology
Journal Volume
271
Journal Issue
10
Start Page
6655
End Page
6666
ISSN
1432-1459
Date Issued
2024-10
Author(s)
Conceição, Isabel
Berk, John L
Weiler, Markus
Kowacs, Pedro A
Dasgupta, Noel R
Khella, Sami
Attarian, Shahram
Kwoh, T Jesse
Jung, Shiangtung W
Chen, Jersey
Viney, Nicholas J
Yu, Rosie Z
Gertz, Morie
Masri, Ahmad
Cruz, Márcia Waddington
Coelho, Teresa
Abstract
BACKGROUND: The phase 3 NEURO-TTRansform trial showed eplontersen treatment for 65 weeks reduced transthyretin (TTR), halted progression of neuropathy impairment, and improved quality of life (QoL) in adult patients with hereditary TTR-mediated amyloidosis with polyneuropathy (ATTRv-PN), vs. historical placebo. METHODS: NEURO-TTRansform enrolled patients with ATTRv-PN. A subset of patients were randomized to receive subcutaneous inotersen 300 mg weekly (Weeks 1-34) and subsequently switched to subcutaneous eplontersen 45 mg every 4 weeks (Weeks 37-81). Change in serum TTR and treatment-emergent adverse events (TEAEs) were evaluated through Week 85. Effects on neuropathy impairment, QoL, and nutritional status were also evaluated. RESULTS: Of 24 patients randomized to inotersen, 20 (83%) switched to eplontersen at Week 37 and four discontinued due to AEs/investigator decision. Absolute change in serum TTR was greater after switching from inotersen (-74.3%; Week 35) to eplontersen (-80.6%; Week 85). From the end of inotersen treatment, neuropathy impairment and QoL were stable (i.e., did not progress) while on eplontersen, and there was no deterioration in nutritional status. TEAEs were fewer with eplontersen (Weeks 37-85; 19/20 [95%] patients) compared with inotersen (up to Week 35; 24/24 [100%] patients). Mean platelet counts decreased during inotersen treatment (mean nadir reduction ‒40.7%) and returned to baseline during eplontersen treatment (mean nadir reduction, ‒3.2%). CONCLUSIONS: Switching from inotersen to eplontersen further reduced serum TTR, halted disease progression, stabilized QoL, restored platelet count, and improved tolerability, without deterioration in nutritional status. This supports a positive benefit-risk profile for patients with ATTRv-PN who switch from inotersen to eplontersen.
Subjects
Amyloidosis
Antisense oligonucleotide
Transthyretin
Treatment efficacy
Treatment safety
Type
journal article