Switching from inotersen to eplontersen in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: analysis from NEURO-TTRansform.

Autor: Conceição I; ULS Santa Maria, CAML, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. imsconceicao@gmail.com., Berk JL; Boston University School of Medicine, Boston, MA, USA., Weiler M; Amyloidosis Center and Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany., Kowacs PA; Instituto de Neurologia de Curitiba, Curitiba, Paraná, Brazil., Dasgupta NR; Indiana University School of Medicine, Indianapolis, IN, USA., Khella S; University of Pennsylvania School of Medicine, Philadelphia, PA, USA., Chao CC; National Taiwan University Hospital, Taipei, Taiwan., Attarian S; Neuromuscular Disorders and ALS Department, Centre Hospitalier Universitaire La Timone, Marseille, France., Kwoh TJ; Clinical Development, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA., Jung SW; Clinical Development, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA., Chen J; Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MA, USA., Viney NJ; Clinical Development, Ionis Pharmaceuticals, Inc., Carlsbad, CA, USA., Yu RZ; Preclinical Development, Ionis Pharmaceuticals, Inc, Carlsbad, CA, USA., Gertz M; Mayo Clinic, Rochester, MN, USA., Masri A; OHSU Center for Hypertrophic Cardiomyopathy and Amyloidosis, Portland, OR, USA., Cruz MW; CEPARM, Amyloidosis Center, University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Coelho T; Centro Hospitalar Universitário de Santo António, Porto, Portugal.
Jazyk: angličtina
Zdroj: Journal of neurology [J Neurol] 2024 Oct; Vol. 271 (10), pp. 6655-6666. Date of Electronic Publication: 2024 Aug 13.
DOI: 10.1007/s00415-024-12616-6
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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