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A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis

2020Journal article Open access
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dc.contributor.authorCoelho, Teresa
dc.contributor.authorAdams, David
dc.contributor.authorConceição, Isabel
dc.contributor.authorWaddington-Cruz, Márcia
dc.contributor.authorSchmidt, Hartmut H.
dc.contributor.authorBuades, Juan
dc.contributor.authorCampistol, Josep
dc.contributor.authorBerk, John L.
dc.contributor.authorPolydefkis, Michael
dc.contributor.authorWang, Jing Jing
dc.contributor.authorChen, Jihong
dc.contributor.authorSweetser, Marianne T.
dc.contributor.authorGollob, Jared
dc.contributor.authorSuhr, Ole B.
dc.date.accessioned2022-06-30T11:14:58Z
dc.date.available2022-06-30T11:14:58Z
dc.date.issued2020
dc.descriptionThe study was registered at ClinicalTrials.gov (identifier: NCT01961921 ) on October 14, 2013pt_PT
dc.description.abstractBackground: Patisiran, an RNA interference therapeutic, has demonstrated robust reduction of wild-type and mutant transthyretin protein and was able to improve polyneuropathy and quality of life following 18 months of treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. In this 24-month Phase II open-label extension study, we evaluated the effects of patisiran treatment (0.3 mg/kg intravenously every 3 weeks) on safety, serum transthyretin levels, and clinical parameters. Efficacy assessments included modified Neuropathy Impairment Score +7 (mNIS+7) and multiple disease-relevant measures. Cardiac assessments were performed in a pre-specified cardiac subgroup. Results: Twenty-seven patients entered this study, including 12 (44%) with ambulation difficulties due to their neuropathy and 11 (41%) who met criteria for the cardiac subgroup. During treatment, the majority of adverse events were mild/moderate in severity; there were no drug-related adverse events leading to treatment discontinuation. The most common drug-related adverse events were flushing and infusion-related reactions (22% each). Patisiran resulted in rapid, robust (~ 82%), and sustained reduction of mean transthyretin levels over 24 months. A mean 6.95-point decrease (improvement) in mNIS+7 from baseline was observed at 24 months. Patisiran's impact on mNIS+7 was irrespective of concomitant tafamidis or diflunisal use, sex, or age. Clinical assessments of motor function, autonomic symptoms, disease stage, and quality of life remained stable over 24 months. No significant changes were observed for echocardiographic measures or cardiac biomarkers in the cardiac subgroup. Exploratory analyses demonstrated improvements in nerve-fiber density with corresponding reductions in amyloid burden observed in skin biopsies over 24 months. Conclusions: Long-term treatment with patisiran had an acceptable safety profile and was associated with halting/improvement of polyneuropathy progression in patients with hATTR amyloidosis.pt_PT
dc.description.sponsorshipAlnylam Pharmaceuticals funded the study and collaborated with theauthors in the study design, collection, analysis, and interpretation of datapt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCoelho T, Adams D, Conceição I, et al. A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. Orphanet J Rare Dis. 2020;15(1):179. doi:10.1186/s13023-020-01399-4pt_PT
dc.identifier.doi10.1186/s13023-020-01399-4pt_PT
dc.identifier.issn1750-1172
dc.identifier.urihttp://hdl.handle.net/10400.16/2687
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBioMed Centralpt_PT
dc.relation.publisherversionhttps://ojrd.biomedcentral.com/articles/10.1186/s13023-020-01399-4pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectATTR amyloidosispt_PT
dc.subjectCardiomyopathypt_PT
dc.subjectPatisiranpt_PT
dc.subjectPolyneuropathypt_PT
dc.subjectRNA interferencept_PT
dc.titleA phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceEnglandpt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage179pt_PT
oaire.citation.titleOrphanet Journal of Rare Diseasespt_PT
oaire.citation.volume15pt_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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