Severe Hypertriglyceridemia

CE / CME

Current Challenges and Emerging Treatments for the Management of Severe Hypertriglyceridemia

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Nurses: 1.00 Nursing contact hour

Physicians: maximum of 1.00 AMA PRA Category 1 Credit

Released: January 28, 2024

Expiration: January 29, 2025

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Emerging FCS Therapies

Although dietary modifications and lifestyle interventions are the mainstays of FCS management, a few emerging therapies are on the horizon. As previously mentioned, volanesorsen and olezarsen are ASOs targeting APOC3.19,21,22 There is also plozasiran, a short‑interfering RNA APOC3 inhibitor that essentially inhibits mRNA and silences the APOC3 gene.

APPROACH Trial: Volanesorsen for Severe Hypertriglyceridemia in FCS

The APPROACH trial was a phase III study of volanesorsen for lowering triglycerides in patients with FCS.50 Of note, patients who received volanesorsen experienced an almost 80% reduction of triglycerides. However, a high percentage of participants in the volanesorsen group experienced thrombocytopenia, so this therapy was not approved for use in the United States.

Olezarsen: Phase III Trial for the Treatment of FCS

Next, we have the phase III BALANCE study of olezarsen in patients with FCS. Here, investigators compared the effects of a 50-mg and 80-mg monthly dose of olezarsen vs placebo on change in fasting triglycerides (NCT04568434). We await presentation of this data with a recent press release suggesting the study met its primary endpoint of a reduction in triglyceride levels compared with placebo.51

PALISADE: Phase III Study to Evaluate Efficacy and Safety of ARO-APOC3 in Individuals With FCS

Plozasiran, the RNA inhibitor, is currently under investigation in the ongoing phase III PALISADE study for individuals with FCS refractory to standard therapy (NCT05089084). The primary endpoints of this study are the percent change from baseline in fasting triglyceride levels at 10 months and 12 months post treatment.