Volanesorsen significantly reduces triglyceride levels in patients with multifactorial chylomicronemia syndrome and may reduce acute pancreatitis events in these patients, according to results of the COMPASS trial.
In an earlier study, the researchers found that lowering hepatic apolipoprotein C-III (APOC3) synthesis with the antisense oligonucleotide volanesorsen effectively lowered triglycerides in patients with familial chylomicronemia syndrome.
The COMPASS phase-3 study explored the safety and efficacy of volanesorsen in patients with multifactorial chylomicronemia syndrome, also known as multifactorial severe hypertriglyceridemia.
COMPASS included 113 patients with multifactorial severe hypertriglyceridemia or familial chylomicronemia syndrome, who had a BMI of 45 kg/m2 or less and fasting plasma triglyceride of 500 mg/dL or higher.
By random assignment, 76 patients received subcutaneous volanesorsen (300 mg) once a week for 26 weeks and 38 received a matched volume of placebo. After 13 weeks of treatment, dosing was changed to 300 mg of volanesorsen or placebo every two weeks, except in patients who had completed at least five months of treatment.
The efficacy of treatment was independent of the type of genetic variants impairing lipoprotein lipase activity, which is a new finding that reinforces the notion that volanesorsen operates via lipoprotein lipase-independent mechanisms – eg, by inhibiting the production of triglyceride-rich lipoproteins.