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Article History

Received: 22 September 2025

Accepted: 22 April 2026

First Online: 27 May 2026

Declarations

:

: This study was funded by Alnylam Pharmaceuticals Inc. The funder collaborated with the authors during the study design, data collection, data analysis, data interpretation, and writing of the report. All authors had full access to all the data in the study and took final responsibility for the decision to submit the manuscript for publication.

: M.F. reports research support from AstraZeneca; consultancy and/or advisory board membership for Alexion, Alnylam Pharmaceuticals, Attralus, Caelum Biosciences, Intellia Therapeutics, Ionis Pharmaceuticals, Janssen Pharmaceuticals, Lexeo Therapeutics, Novo Nordisk, Pfizer, and Prothena; support for attending meetings from Alnylam Pharmaceuticals, AstraZeneca, and Attralus; and ownership of equity in Lexeo Therapeutics and Mycardium. V.A. reports consulting fees and research funding from Alnylam Pharmaceuticals, AstraZeneca, Bayer, Biotronik, and Pfizer. P.G.-P. reports speaking fees from Alnylam Pharmaceuticals, AstraZeneca, BridgeBio, Intellia Therapeutics, Ionis Pharmaceuticals, Novo Nordisk, and Pfizer; consulting fees from Alexion, Alnylam Pharmaceuticals, AstraZeneca, Attralus, Bayer, BridgeBio, Intellia Therapeutics, Ionis Pharmaceuticals, Neuroimmune, Novo Nordisk, and Pfizer; and research/educational support to their institution from Alnylam Pharmaceuticals, AstraZeneca, BridgeBio, Intellia Therapeutics, Novo Nordisk, and Pfizer. M.S.M. reports receiving research support from Alnylam Pharmaceuticals, Attralus, BridgeBio, Intellia Therapeutics, and Ionis Pharmaceuticals; and consulting fees from Akcea Therapeutics, Alnylam Pharmaceuticals, AstraZeneca, Intellia Therapeutics, Novo Nordisk, and Roche. J.D.G. reports research support from Alnylam Pharmaceuticals; consulting fees from Alnylam Pharmaceuticals, AstraZeneca, BridgeBio, Intellia Therapeutics, Ionis Pharmaceuticals, and Lycia Therapeutics; and payment for lectures or speaker fees from Alnylam Pharmaceuticals and AstraZeneca. F.C. reports consulting fees from Alnylam Pharmaceuticals, AstraZeneca, Bayer, BridgeBio, and Pfizer. K.K., X.G., S.J., G.R., and P.B. are employees of and own shares in Alnylam Pharmaceuticals. N.M. was a previous employee of Alnylam Pharmaceuticals and own shares in Alnylam Pharmaceuticals.

: The studies were conducted in accordance with all applicable regulatory requirements, the International Council for Harmonisation Good Clinical Practice guidelines, and the principles of the Declaration of Helsinki. The institutional review board or independent ethics committee at each center approved the study protocol and amendments.

: Access to anonymized individual participant data that support these results is made available 12 months after trial completion and not less than 12 months after the product and indication have been approved in the USA and/or the EU. Data 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: .

: MF, VA, PG-P, MSM, JDG and FC were responsible for the acquisition of the data. XG was responsible for data analysis. All authors contributed to the interpretation of the data and the development and final approval of the manuscript. All authors take accountability for the work.

: Consent was obtained from participants in all trials.

: Written informed consent was obtained for all participants before conducting any study procedures.