Akcea and Ionis announced positive findings from the APPROACH study, a Phase 3 trial of volanesorsen for the reduction of triglycerides in patients with familial chylomicronemia syndrome (FCS).
FCS is a rare genetic disorder associated with severe hypertriglyceridemia with the risk of recurrent, potentially fatal pancreatitis. A deficiency in lipoprotein lipase is the cause of the inability to clear large, triglyceride-rich lipid particles called chylomicrons, which results in extremely high levels of triglycerides in the bloodstream. There is currently no effective drug therapy available for FCS.
APPROACH is a randomized, double-blind, placebo-controlled, 52-week Phase 3 trial evaluating the efficacy and safety of volanesorsen in FCS. Patients enrolled in the study (n=66) had an average incoming triglyceride level of 2,209 mg/dL. The primary endpoint was the mean reduction in triglycerides from baseline after 3 months of treatment.
The study achieved its primary endpoint, showing that treatment with volanesorsen was associated with a statistically significant mean reduction in triglycerides of 77% from baseline after 3 months of therapy (mean absolute reduction of 1,712 mg/dL) compared to a mean increase of 18% in the placebo arm (P<0.0001). The treatment effect observed was sustained over the 52-week treatment period. Additionally, patients with the highest documented frequency of pancreatitis attacks in the volanesorsen arm experienced no attacks over 52 weeks (P=0.02).
Volanesorsen was found to be safe, with mild injection site reactions as the most common adverse event. Declines in platelet counts due to decreases in triglycerides were observed, but were generally well managed with dose adjustment. No treatment-related liver or renal adverse events, including no increases in liver fat, were observed in the study.
Data from the APPROACH study will support the regulatory submission of volanesorsen for FCS. Detailed study findings will be presented at an upcoming medical meeting.
Volanesorsen is an antisense drug designed to reduce the production of ApoC-III.