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Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial

2022Journal article Open access
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dc.contributor.authorAdams, David
dc.contributor.authorTournev, Ivailo L.
dc.contributor.authorTaylor, Mark S.
dc.contributor.authorCoelho, Teresa
dc.contributor.authorPlanté-Bordeneuve, Violaine
dc.contributor.authorBerk, John L.
dc.contributor.authorGonzález-Duarte, Alejandra
dc.contributor.authorGillmore, Julian D.
dc.contributor.authorLow, Soon-Chai
dc.contributor.authorSekijima, Yoshiki
dc.contributor.authorObici, Laura
dc.contributor.authorChen, Chongshu
dc.contributor.authorBadri, Prajakta
dc.contributor.authorArum, Seth M.
dc.contributor.authorVest, John
dc.contributor.authorPolydefkis, Michael
dc.date.accessioned2024-06-17T08:09:45Z
dc.date.available2024-06-17T08:09:45Z
dc.date.issued2022
dc.description.abstractBackground: The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. Methods: HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months. Results: HELIOS-A enrolled 164 patients (vutrisiran, n = 122; patisiran reference group, n = 42); external placebo, n = 77. Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (p = 3.54 × 10-12), and all secondary efficacy endpoints; significant improvements versus external placebo were observed in Norfolk Quality of Life-Diabetic Neuropathy, 10-meter walk test (both at 9 and 18 months), mNIS+7, modified body-mass index, and Rasch-built Overall Disability Scale (all at 18 months). TTR reduction with vutrisiran Q3M was non-inferior to within-study patisiran Q3W. Most adverse events were mild or moderate in severity, and consistent with ATTRv amyloidosis natural history. There were no drug-related discontinuations or deaths. Conclusions: Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile.pt_PT
dc.description.sponsorshipThis study was funded by Alnylam Pharmaceuticals Inc. The fundercollaborated with authors during study design, data collection, dataanalysis, data interpretation, and writing of the report. All authors hadfull access to all the data in the study and had final responsibility forthe decision to submit for publication.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAdams D, Tournev IL, Taylor MS, et al. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid. 2023;30(1):1-9. doi:10.1080/13506129.2022.2091985pt_PT
dc.identifier.doi10.1080/13506129.2022.2091985pt_PT
dc.identifier.issn1350-6129
dc.identifier.issn1744-2818
dc.identifier.urihttp://hdl.handle.net/10400.16/2916
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherTaylor & Francispt_PT
dc.relation.publisherversionhttps://www.tandfonline.com/doi/full/10.1080/13506129.2022.2091985pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectATTRv amyloidosispt_PT
dc.subjectRNA interferencept_PT
dc.subjecthATTR amyloidosispt_PT
dc.subjectpatisiranpt_PT
dc.subjectvutrisiranpt_PT
dc.titleEfficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trialpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceEnglandpt_PT
oaire.citation.endPage26pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage18pt_PT
oaire.citation.titleAmyloidpt_PT
oaire.citation.volume30pt_PT
person.familyNameCoelho
person.givenNameTeresa
person.identifier.ciencia-idC71E-3343-F445
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationca69c0a3-d48a-4b92-bbf7-c17288d609b7
relation.isAuthorOfPublication.latestForDiscoveryca69c0a3-d48a-4b92-bbf7-c17288d609b7

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