A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis
| Main Author: | |
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| Publication Date: | 2020 |
| Other Authors: | , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Download full: | http://hdl.handle.net/10400.16/2687 |
Summary: | The study was registered at ClinicalTrials.gov (identifier: NCT01961921 ) on October 14, 2013 |
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A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosisATTR amyloidosisCardiomyopathyPatisiranPolyneuropathyRNA interferenceThe study was registered at ClinicalTrials.gov (identifier: NCT01961921 ) on October 14, 2013Background: 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.Alnylam Pharmaceuticals funded the study and collaborated with theauthors in the study design, collection, analysis, and interpretation of dataBioMed CentralRepositório Científico do Centro Hospitalar Universitário de Santo AntónioCoelho, TeresaAdams, DavidConceição, IsabelWaddington-Cruz, MárciaSchmidt, Hartmut H.Buades, JuanCampistol, JosepBerk, John L.Polydefkis, MichaelWang, Jing JingChen, JihongSweetser, Marianne T.Gollob, JaredSuhr, Ole B.2022-06-30T11:14:58Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/2687engCoelho 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/s13023-020-01399-41750-117210.1186/s13023-020-01399-4info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-20T11:01:42Zoai:repositorio.chporto.pt:10400.16/2687Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:38:52.968284Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis |
| title |
A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis |
| spellingShingle |
A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis Coelho, Teresa ATTR amyloidosis Cardiomyopathy Patisiran Polyneuropathy RNA interference |
| title_short |
A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis |
| title_full |
A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis |
| title_fullStr |
A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis |
| title_full_unstemmed |
A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis |
| title_sort |
A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis |
| author |
Coelho, Teresa |
| author_facet |
Coelho, Teresa Adams, David Conceição, Isabel Waddington-Cruz, Márcia Schmidt, Hartmut H. Buades, Juan Campistol, Josep Berk, John L. Polydefkis, Michael Wang, Jing Jing Chen, Jihong Sweetser, Marianne T. Gollob, Jared Suhr, Ole B. |
| author_role |
author |
| author2 |
Adams, David Conceição, Isabel Waddington-Cruz, Márcia Schmidt, Hartmut H. Buades, Juan Campistol, Josep Berk, John L. Polydefkis, Michael Wang, Jing Jing Chen, Jihong Sweetser, Marianne T. Gollob, Jared Suhr, Ole B. |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório Científico do Centro Hospitalar Universitário de Santo António |
| dc.contributor.author.fl_str_mv |
Coelho, Teresa Adams, David Conceição, Isabel Waddington-Cruz, Márcia Schmidt, Hartmut H. Buades, Juan Campistol, Josep Berk, John L. Polydefkis, Michael Wang, Jing Jing Chen, Jihong Sweetser, Marianne T. Gollob, Jared Suhr, Ole B. |
| dc.subject.por.fl_str_mv |
ATTR amyloidosis Cardiomyopathy Patisiran Polyneuropathy RNA interference |
| topic |
ATTR amyloidosis Cardiomyopathy Patisiran Polyneuropathy RNA interference |
| description |
The study was registered at ClinicalTrials.gov (identifier: NCT01961921 ) on October 14, 2013 |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z 2022-06-30T11:14:58Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.16/2687 |
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http://hdl.handle.net/10400.16/2687 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Coelho 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/s13023-020-01399-4 1750-1172 10.1186/s13023-020-01399-4 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
BioMed Central |
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BioMed Central |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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