The U.S. Food and Drug Administration (FDA) has granted Priority Review to Ionis Pharmaceuticals' New Drug Application (NDA) for olezarsen, an investigational RNA-targeted medicine aimed at treating adults with familial chylomicronemia syndrome (FCS). The FDA has set a target action date of December 19, 2024, and indicated that it does not plan to hold an advisory committee meeting for this application.
Brett Monia, Ph.D., CEO of Ionis, emphasized the urgent need for new treatments, stating, "FCS is a debilitating, rare, genetic disease that causes significant physical, emotional and financial burden with no approved treatment options in the U.S." He added that the Priority Review underscores the potential of olezarsen to lower triglyceride levels and reduce the incidence of life-threatening acute pancreatitis events.
The application is based on positive results from the Balance study, a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial. The study's findings were presented at the 2024 American College of Cardiology (ACC) Annual Meeting and published in The New England Journal of Medicine (NEJM). The FDA had previously granted olezarsen Fast Track designation in January 2023, as well as Orphan Drug and Breakthrough Therapy designations in February 2024. Ionis is also planning regulatory filings in the European Union.
Olezarsen's Mechanism of Action
Olezarsen is a ligand conjugated antisense (LICA) medicine designed to lower the body's production of apolipoprotein C-III (apoC-III), a protein produced in the liver that regulates triglyceride metabolism in the blood. By reducing apoC-III, olezarsen aims to improve triglyceride levels in patients with FCS and severe hypertriglyceridemia (sHTG).
Ongoing Clinical Trials for Severe Hypertriglyceridemia (sHTG)
Ionis is also evaluating olezarsen for the treatment of sHTG in three Phase 3 clinical trials: CORE, CORE2, and ESSENCE. Enrollment for all three trials was completed in the first half of 2024. CORE and CORE2 enrolled over 1,000 sHTG patients with fasting triglyceride levels ≥500 mg/dL, while ESSENCE enrolled over 1,400 patients with fasting triglyceride levels ≥150 mg/dL to <500 mg/dL at risk for atherosclerotic cardiovascular disease, as well as patients with fasting triglycerides ≥500 mg/dL. Data from these trials are expected in the second half of 2025.
Familial Chylomicronemia Syndrome (FCS) and Severe Hypertriglyceridemia (sHTG)
FCS is a rare genetic disease characterized by extremely elevated triglyceride levels due to impaired lipoprotein lipase (LPL) function. This condition affects an estimated one to 13 people per million in the U.S. Patients with FCS are at high risk of acute pancreatitis and other chronic health issues and currently rely on restrictive diets for management.
sHTG is defined by triglyceride levels of 500 mg/dL and above, affecting an estimated three million people in the U.S. sHTG can lead to pancreatitis and cardiovascular complications. Current treatment guidelines recommend lifestyle interventions and triglyceride-lowering medications; however, new treatments are needed to further reduce triglyceride levels and the risk of pancreatitis in these patients.
