Volanesorsen and triglyceride levels in familial chylomicronemia syndrome: long-term efficacy and safety data from patients in an open-label extension trial.
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Witztum, Joseph LGaudet, Daniel
Arca, Marcello
Jones, Alan
Soran, Handrean
Gouni-Berthold, Ioanna
Stroes, Erik S G
Alexander, Veronica J
Jones, Richard
Watts, Lynnetta
Xia, Shuting
Tsimikas, Sotirios
Publication date
2023-03-22
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Background: Familial chylomicronemia syndrome (FCS) is a rare, autosomal recessive genetic disorder characterized by a marked increase in plasma triglyceride (TG) levels and recurrent episodes of pancreatitis. The response to conventional TG-lowering therapies is suboptimal. Volanesorsen, an antisense oligonucleotide that targets hepatic apoC-III mRNA, has been shown to significantly reduce TGs in patients with FCS. Objective: To further evaluate the safety and efficacy of extended treatment with volanesorsen in patients with FCS. Methods: This phase 3 open-label extension study evaluated the efficacy and safety of extended treatment with volanesorsen in three groups of patients with FCS: Those who had previously received volanesorsen or placebo in the APPROACH and COMPASS studies, and treatment-naive patients not participating in either study. Key endpoints included change in fasting TG and other lipid measurements, and safety over 52 weeks. Results: Volanesorsen treatment resulted in sustained reductions in plasma TG levels in previously treated patients from the APPROACH and COMPASS studies. Volanesorsen-treated patients from the three populations studied had mean decreases in fasting plasma TGs from index study baseline to months 3, 6, 12 and 24 as follows: decreases of 48%, 55%, 50%, and 50%, respectively (APPROACH); decreases of 65%, 43%, 42%, and 66%, respectively (COMPASS); and decreases of 60%, 51%, 47%, and 46%, respectively (treatment-naive). Common adverse events were injection site reactions and platelet count decrease, consistent with previous studies. Conclusion: Extended open-label treatment with volanesorsen in patients with FCS resulted in sustained reductions of plasma TG levels and safety consistent with the index studies.Citation
Witztum JL, Gaudet D, Arca M, Jones A, Soran H, Gouni-Berthold I, Stroes ESG, Alexander VJ, Jones R, Watts L, Xia S, Tsimikas S. Volanesorsen and triglyceride levels in familial chylomicronemia syndrome: Long-term efficacy and safety data from patients in an open-label extension trial. J Clin Lipidol. 2023 May-Jun;17(3):342-355. doi: 10.1016/j.jacl.2023.03.007. Epub 2023 Mar 22Type
ArticleAdditional Links
http://www.sciencedirect.com/science/journal/19332874PMID
37100699Journal
Journal of Clinical LipidologyPublisher
Elsevierae974a485f413a2113503eed53cd6c53
10.1016/j.jacl.2023.03.007