Reduction of triglycerides with volanesorsen therapy may significantly improve the clinical symptoms and quality of life (QoL) in patients with familial chylomicronemia syndrome (FCS), according to a case report published in the Journal of the Endocrine Society.

Severely high triglycerides are one of the main characteristics of FCS, a rare genetic disorder that is also associated with recurrent acute pancreatitis, abdominal pain, anxiety, and fatigue, leading to substantially reduced QoL.

Ioanna Gouni-Berthold, MD, of the polyclinic for endocrinology, diabetes, and preventive medicine at the University of Cologne in Cologne, Germany, described a case of a 46-year-old woman of Southeast Asian origin with a history of type 2 diabetes, high blood pressure, extremely high triglycerides (>1000 mg/dL), and several episodes of acute pancreatitis that required hospitalization. The patient had a positive family history for high triglycerides in both brothers, with one also having had multiple episodes of acute pancreatitis. Genetic analysis revealed lipoprotein lipase deficiency (compound heterozygote, with 2 mutations in the lipoprotein lipase gene: c.209A>G and c.784C>T).

The patient was previously treated with omega-3 fatty acids, fibrates, and a restricted diet, but her triglyceride levels remained significantly elevated and her symptoms persisted with diminished QoL.

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The patient was enrolled in the COMPASS study (ClinicalTrials.gov Identifier: NCT02300233), which investigated the efficacy of volanesorsen, a second-generation 2′-O-(2-methoxyethyl)-modified antisense inhibitor of apolipoprotein C3 (apoC-III) synthesis, to reduce fasting triglycerides in patients with hypertriglyceridemia. During the initial double-blind phase of the study, there were no changes in triglyceride levels in the patient. During the open-label extension of the study, however, there was a gradual decrease in fasting triglycerides, from 2851 mg/dL to 146 mg/dL after 4 months of therapy with volanesorsen 300 mg weekly, administered subcutaneously.

The drug was tolerated extremely well, with no evidence of any associated side effects. In addition to the marked decrease in triglyceride levels, the patient reported symptomatic improvement, including daily functioning and overall QoL.

“FCS should be suspected in patients with severe [hypertriglyceridemia] with no known secondary cause, which is unresponsive to traditional lipid lowering medications. Despite maintenance of a severely restricted diet, many patients still experience debilitating symptoms and remain at risk for [acute pancreatitis]. Substantial reduction in [triglycerides] with volanesorsen treatment appeared to be associated with noted improvements in clinical symptoms, as well as observed QoL, in a patient with FCS,” concluded Dr Gouni-Berthold.

Disclosure: The study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Reference

Gouni-Berthold I. Significant quality of life improvement observed in patient with FCS associated with a marked reduction in triglycerides [published online December 23, 2019]. J Endocr Soc. doi:10.1210/jendso/bvz035