-
Randomized Controlled Trial
Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial.
- David Adams, Ivailo L Tournev, Mark S Taylor, Teresa Coelho, Violaine Planté-Bordeneuve, John L Berk, Alejandra González-Duarte, Julian D Gillmore, Soon-Chai Low, Yoshiki Sekijima, Laura Obici, Chongshu Chen, Prajakta Badri, Seth M Arum, John Vest, Michael Polydefkis, and HELIOS-A Collaborators.
- Neurology Department, CHU Bicêtre, APHP, Université Paris-Saclay, Le Kremlin Bicêtre Cedex, France.
- Amyloid. 2023 Mar 1; 30 (1): 191-9.
BackgroundThe 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.MethodsHELIOS-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.ResultsHELIOS-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.ConclusionsVutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile.Clinicaltrials.GovNCT03759379.
Notes
Knowledge, pearl, summary or comment to share?You can also include formatting, links, images and footnotes in your notes
- Simple formatting can be added to notes, such as
*italics*
,_underline_
or**bold**
. - Superscript can be denoted by
<sup>text</sup>
and subscript<sub>text</sub>
. - Numbered or bulleted lists can be created using either numbered lines
1. 2. 3.
, hyphens-
or asterisks*
. - Links can be included with:
[my link to pubmed](http://pubmed.com)
- Images can be included with:
![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
- For footnotes use
[^1](This is a footnote.)
inline. - Or use an inline reference
[^1]
to refer to a longer footnote elseweher in the document[^1]: This is a long footnote.
.