https://orcid.org/0000-0003-1096-9627
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Abstract
Background
Longitudinal changes in neurofilament light chain (NfL) levels were evaluated alongside prespecified clinical assessments 24 months into the patisiran Global open-label extension (OLE) study in patients with ATTRv amyloidosis with polyneuropathy.
Methods
All patients enrolled in the Global OLE, from phase III APOLLO and phase II OLE parent studies, received patisiran. Assessments included measures of polyneuropathy (modified Neuropathy Impairment Score+7 (mNIS+7)), quality of life (QOL; Norfolk QOL-Diabetic Neuropathy questionnaire (Norfolk QOL-DN)), and plasma NfL.
Results
Patients receiving patisiran in the parent study (APOLLO-patisiran, n = 137; phase II OLE-patisiran, n = 25) demonstrated sustained improvements in mNIS+7 (mean change from parent study baseline (95% confidence interval): APOLLO-patisiran −4.8 (−8.9, −0.6); phase II OLE-patisiran −5.8 (−10.5, −1.2)) and Norfolk QOL-DN (APOLLO-patisiran −2.4 (−7.2, 2.3)), and maintained reduced NfL levels at Global OLE 24 months. After initiating patisiran in the Global OLE, APOLLO-placebo patients (n = 49) demonstrated stabilized mNIS+7, improved Norfolk QOL-DN, and significantly reduced NfL levels. Patisiran continued to demonstrate an acceptable safety profile. Earlier patisiran initiation was associated with a lower exposure-adjusted mortality rate.
Conclusions
Long-term patisiran treatment led to sustained improvements in neuropathy and QOL, with NfL demonstrating potential as a biomarker for disease progression and treatment response in ATTRv amyloidosis with polyneuropathy.
Correction Statement
This article was originally published with errors, which have now been corrected in the online version. Please see Correction (http://dx.doi.org/10.1080/13506129.2023.2246797)
Acknowledgments
The authors thank the patients and their families for their valued contribution to this study and the members of the patisiran Global OLE collaborators for their work on the study (patisiran Global OLE collaborators list is available here). This study was funded by Alnylam Pharmaceuticals (Cambridge, MA, USA). Medical writing support was provided by Ed Childs of Adelphi Communications (Macclesfield, UK), in accordance with Good Publication Practice guidelines, funded by Alnylam Pharmaceuticals.
Disclosure statement
ST, EA, JV, and PN are all employed by Alnylam Pharmaceuticals and report ownership of shares in Alnylam Pharmaceuticals. CH was employed by Alnylam Pharmaceuticals at the time of this analysis and reports ownership of shares in Alnylam Pharmaceuticals. MP has participated in clinical trials sponsored by Akcea, Alnylam Pharmaceuticals, and Pfizer, and has received consulting fees from Akcea, Alnylam Pharmaceuticals, Biogen-Idec, Pfizer, and Vertex Pharmaceutical. DA has participated in clinical trials sponsored by Akcea and Alnylam Pharmaceuticals, and has received consulting fees advisory from Alnylam Pharmaceuticals, Bridgebio, Pfizer, and AstraZeneca. TC has participated in clinical trials sponsored by Akcea, Alnylam Pharmaceuticals, Eidos, Ionis, Prothena, and Pfizer. MU reports grants, personal fees, and non-financial support from Alnylam Pharmaceuticals and Pfizer; grants from Prothena; and personal fees from Janssen Pharmaceutical K.K., outside the submitted work.
Data availability statement
Anonymized individual participant data that support these results would be made available in a secure-access environment 12 months after study completion and when the product and indication have been approved for no less than 12 months in the US and/or the EU.
Access will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.