Treatment with Volanesorsen (VLN) Reduced Triglycerides and Pancreatitis in Patients with FCS and sHTG vs Placebo: Results of the APPROACH and COMPASS Studies

Gelrud, Andrés; Digenio, Andrés; Alexander, Veronica J.; Williams, Karren; Hsieh, Andrew C.; Gouni-Berthold, I; Bruckert, Éric; Stroes, Erik S.G.; Geary, Richard S.; Hughes, Steven J.; Tsimikas, Sotirios; Gaudet, Daniel

doi:10.1016/j.atherosclerosissup.2018.04.476

Cited by 5 publications

(2 citation statements)

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“…Two recent phase III trials, the APPROACH and COMPASS, with respectively 66 patients with FCS and 113 patients with HTG showed a reduction in plasma TG levels between 70% and 80% [62,63]. In a combined analysis of these studies, volanesorsen showed a significant reduction in pancreatitis, with 1 occurring pancreatitis in the volanesorsen group versus 9 pancreatitides in the placebo group (p = 0.0185) [64,65]. It should be noted that, in the APPROACH trial, declines in platelet counts led to discontinuation of volanesorsen in five patients, which resulted in complete recovery of platelet counts.…”

Section: Article Highlightsmentioning

confidence: 98%

Targeting apoC-III and ANGPTL3 in the treatment of hypertriglyceridemia

Nurmohamed

Thie

Stroes

2020

Expert Review of Cardiovascular Therapy

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Introduction: The prevalence of hypertriglyceridemia (HTG) is increasing. Elevated triglyceride (TG) levels are associated with an increased cardiovascular disease (CVD) risk. Moreover, severe HTG results in an elevated risk of pancreatitis, especially in severe HTG with an up to 350-fold increased risk. Both problems emphasize the clinical need for effective TG lowering. Areas covered: The purpose of this review is to discuss the currently available therapies and to elaborate the most promising novel therapeutics for TG lowering. Expert opinion: Conventional lipid lowering strategies do not efficiently lower plasma TG levels, leaving a residual CVD and pancreatitis risk. Both apolipoprotein C-III (apoC-III) and angiopoietin-like 3 (ANGPTL3) are important regulators in TG-rich lipoprotein (TRL) metabolism. Several novel agents targeting these linchpins have ended phase II/III trials. Volanesorsen targeting apoC-III has shown reductions in plasma TG levels up to 90%. Multiple ANGPLT3 inhibitors (evinacumab, IONIS-ANGPTL3-L Rx , ARO-ANG3) effectuate TG reductions up to 70% with concomitant potent reduction in all other apoB containing lipoprotein fractions. We expect these therapeutics to become players in the treatment for (especially) severe HTG in the near future.

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Section: Article Highlightsmentioning

confidence: 98%

Targeting apoC-III and ANGPTL3 in the treatment of hypertriglyceridemia

Nurmohamed

Thie

Stroes

2020

Expert Review of Cardiovascular Therapy

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“…Volanesorsen is an antisense oligonucleotide against Apo-CIII mRNA that robustly decreases triglyceride and ApoCIII concentrations through lipoprotein lipase independent pathways (Figure 4). Randomized controlled clinical trials have found reductions of about 70% in triglyceride levels and a reduced risk of acute pancreatitis associated with hypertriglyceridemia [52]. A major step forward in the treatment of rare diseases was made in patients with familial chylomicronemia syndrome, a rare and potentially fatal genetic disorder due to loss of lipoprotein lipase activity, characterized by chylomicronemia with recurrent pancreatitis and few therapeutic options.…”

Section: Volanesorsenmentioning

confidence: 99%

Do we need new lipid-lowering agents in the era of PCSK9 inhibitors? Recent advances

2022

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Atherosclerotic disease remains the leading cause of death worldwide. Much of atherosclerotic disease initiation and progression is driven by dyslipidemia. With the advent of statins, ezetimibe, and more recently the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, physicians across all specialties have access to an armamentarium to address this major pathophysiological driver. Nevertheless, there is still a large unmet need in terms of optimizing pharmacotherapeutic lipid lowering strategies. This article will review the evidence pertaining to the major lipid-lowering agents that have been introduced lately, or still are under development, after the advent of statins, ezetimibe and PCSK9 inhibitors. There is cumulating evidence suggesting that there soon will be a broad specter of differential therapies across a variety of mechanistic pathways that will enter clinical medicine. Knowledge about these potential recent advances and various upcoming therapeutic options will make choice easier for physicians, and will lead to more personalized selections of available treatments.

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How to Deal with the Etiological Diagnosis of Acute Pancreatitis in Clinical Practice?

Jagannath

Garg

2021

Clinical Pancreatology for Practising Gastroenterologists and Surgeons

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Treatment with Volanesorsen (VLN) Reduced Triglycerides and Pancreatitis in Patients with FCS and sHTG vs Placebo: Results of the APPROACH and COMPASS Studies

Cited by 5 publications

References 0 publications

Targeting apoC-III and ANGPTL3 in the treatment of hypertriglyceridemia

Targeting apoC-III and ANGPTL3 in the treatment of hypertriglyceridemia

Do we need new lipid-lowering agents in the era of PCSK9 inhibitors? Recent advances

How to Deal with the Etiological Diagnosis of Acute Pancreatitis in Clinical Practice?

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