Study: Olezarsen Reduces Triglycerides in Familial Chylomicronemia Syndrome

A recent phase 3, double-blind, placebo-controlled trial has shown that olezarsen reduces plasma triglyceride levels and the frequency of acute pancreatitis in patients with familial chylomicronemia syndrome (FCS).

Familial chylomicronemia syndrome is a rare genetic disorder characterized by extreme hypertriglyceridemia and a high risk of recurrent acute pancreatitis. Current management options are limited, so the researchers aimed to identify a potential novel therapy targeting the underlying pathophysiology. Olezarsen, an antisense oligonucleotide that reduces hepatic synthesis of apolipoprotein C-III, has shown potential in addressing the elevated triglyceride levels central to FCS. This trial sought to evaluate olezarsen’s efficacy and safety in this patient population.

In the study, 66 patients with genetically confirmed FCS were randomized to receive olezarsen at doses of 80 mg or 50 mg, or placebo, administered subcutaneously every 4 weeks for 49 weeks. The primary endpoints were the percent change in fasting triglyceride levels from baseline to 6 months, with secondary endpoints assessing apolipoprotein C-III levels and incidence of acute pancreatitis. Patients had a baseline mean triglyceride level of 2630 mg/dL, and 71% had experienced acute pancreatitis in the previous decade.

Patients receiving the 80 mg dose of olezarsen showed a significant reduction in fasting triglyceride levels at 6 months compared with placebo (-43.5 percentage points; 95% CI, -69.1 to -17.9; P <.001). The 50-mg dose demonstrated a reduction of -22.4 percentage points (95% CI, -47.2 to 2.5; P = .08). Apolipoprotein C-III levels decreased by 73.7 percentage points in the 80-mg group and 65.5 percentage points in the 50-mg group compared to placebo. Acute pancreatitis episodes were lower in the olezarsen groups, with only one episode in each treatment arm compared to 11 in the placebo group (rate ratio, 0.12; 95% CI, 0.02 to 0.66). Adverse events were generally mild to moderate, with four patients in the 80 mg group experiencing events attributed to olezarsen.

“In patients with familial chylomicronemia syndrome, olezarsen may represent a new therapy to reduce plasma triglyceride levels,” the study authors concluded.

Reference
Olezarsen, acute pancreatitis, and familial chylomicronemia syndrome. N Engl J Med. 2024;390(19):1781-1792. doi: 10.1056/NEJMoa2400201