Volanesorsen and triglyceride levels in familial chylomicronemia syndrome: Long-term efficacy and safety data from patients in an open-label extension trial

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,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 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 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.& COPY; 2023 National Lipid Association. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )