Volanesorsen: A New Era in the Treatment of Severe Hypertriglyceridemia.

Genovefa Kolovou,Niki Katsiki,Vana Kolovou

doi:10.3390/jcm11040982

Genovefa Kolovou, Niki Katsiki + Show 1 more

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https://doi.org/10.3390/jcm11040982

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Abstract

Introduction: Familial chylomicronemia syndrome (FCS) is a rare inherited disease, mainly due to lipoprotein lipase (LPL) gene mutations, leading to lipid abnormalities. Volanesorsen, a second-generation 2′-O-methoxyethyl (2′-MOE) chimeric antisense therapeutic oligonucleotide, can decrease plasma apolipoprotein C3 and triglycerides (TG) levels through LPL-independent pathways. The European Medicines Agency has approved volanesorsen as an adjunct to diet in adult FCS patients with an inadequate response to TG-lowering therapy. Areas covered: Available clinical data on volanesorsen efficacy and safety are presented. Furthermore, we discuss the yearly treatment with volanesorsen of a 21-year-old female FCS patient with LPL mutation. Volanesorsen was well-tolerated and decreased patient’s TG levels (from >5000 mg/dL (56 mmol/L) to 350–500 mg/dL (4–5.6 mmol/L)) at 12 months. Lipoprotein apheresis (LA) was stopped and there were no episodes of pancreatitis or abdominal pain. Expert opinion: Severe hypertriglyceridemia can potentially be fatal. Until recently, there was no specific treatment for FCS, apart from hypotriglyceridemic diet, fibrates, omega-3 fatty acids, and LA sessions. Therefore, volanesorsen represents a promising therapeutic solution for these patients. The main side effect of volanesorsen therapy is thrombocytopenia, which should be monitored and treated accordingly. Increasing evidence will further elucidate the clinical implications of volanesorsen use in daily practice.

Highlights

Hypertriglyceridemia is defined as mild/moderate (plasma triglyceride (TG): 150–499 mg/dL (1.7–5.6 mmol/L)), severe (plasma TG: >500 mg/dL (5.6 mmol/L)), or extreme (>2000 mg/dL (22 mmol/L)) and can be fatal, as shown in a series of 221 patients with TG-induced pancreatitis [1]
Volanesorsen can be considered in the treatment of patients with severe hypertriglyceridemia or familial chylomicronemia syndrome (FCS) to lower their elevated TG and apoC3 levels, prevent acute pancreatitis recurrence and improve their symptoms, facilitating their professional, social, and personal life
EMA has approved volanesorsen as an adjunct to diet in adult patients with

Summary

Introduction

Hypertriglyceridemia is defined as mild/moderate (plasma triglyceride (TG): 150–499 mg/dL (1.7–5.6 mmol/L)), severe (plasma TG: >500 mg/dL (5.6 mmol/L)), or extreme (>2000 mg/dL (22 mmol/L)) and can be fatal, as shown in a series of 221 patients with TG-induced pancreatitis [1]. (LMF-1), and glycosylphosphatidylinositol-anchored high-density lipoprotein–binding protein 1 (GPIHBP1) [4]. All these mutations can lead to lipid abnormalities. In patients with FCS, fasting plasma has a milky, white appearance, and, if left undisturbed for some hours, a creamy layer of CMs can be clearly observed on the top [5]. FCS can be diagnosed in childhood or early adulthood due to the accumulation of CMs in the plasma, causing eruptive xanthomas, lipemia retinalis (visible intraarterial hypertriglyceridemia), recurrent incidents of abdominal pain and/or pancreatitis, milky white plasma (large increase in plasma CM levels) and TG levels > 1000 mg/dL (11 mmol/L).

Case Presentation

Clinical Data on Volanesorsen Efficacy and Safety

Conclusions

Expert Opinion