1. Triglyceride levels in familial chylomicronemia patients were notably reduced when treated with the apolipoprotein C-III antisense mediated inhibitor volanesorsen compared to placebo treated patients.
2. Patients treated with volanesorsen experienced thrombocytopenia and injection site reactions, and a notable number of volanesorsen patients discontinued the trial due to treatment related adverse events.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Reduced or absent lipoprotein lipase (LPL) activity is characteristic of familial chylomicronemia syndrome. LPL breaks down serum triglycerides, and its dysfunction results in markedly elevated triglyceride levels that clinically results in a multitude of symptoms including abdominal pain and recurrent pancreatitis. Volanesorsen is an antisense therapeutic that reduces apolipoprotein C-III (APOC3) mRNA, as APOC3 is a risk factor for hypertriglyceridemia. In this phase 3 randomized controlled trial patients randomized to receive volanesorsan for 3 months had a marked reduction in triglyceride levels compared to placebo treated patients. Patients in the treatment group experienced injection site reactions and thrombocytopenia as adverse events.
This randomized trial shows clinical biomarker promise of a potential first-in-class therapy for familial chylomicronemia. Longer term follow-up and confirmation that treatment reduces disease complications such as pancreatitis will provide clinical substantiation for the utility of this treatment.