Tryngolza Approved for Familial Chylomicronemia Syndrome

On Dec. 19, 2024, the US Food and Drug Administration (FDA) approved Tryngolza^™ (olezarsen – Ionis Pharmaceuticals) in adults with familial chylomicronemia syndrome (FCS). Tryngolza is a first-in-class RNA-targeted therapy designed to inhibit the production of apolipoprotein C-III (ApoC-III), a key regulator of triglyceride metabolism. This is the only treatment currently approved for FCS. The recommended dose is 80mg injected subcutaneously (SC) once monthly into the abdomen or the front of the thigh. The launch is expected by the end of the year, and the cost will be $595,000 annually. For full prescribing information, please click here.

At a Glance

• Brand Drug: Tryngolza(olezarsen)
• Manufacturer: Ionis Pharmaceuticals
• Date Approved: Dec. 19, 2024
• Indication:  As an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS)
• Dosage Forms Available: 80mg/0.8mL in a single dose autoinjector for SC injection
• Launch Date: Expected by year end
• Estimated Annual Cost: $595,000
• FDA Designation(s): Priority Review. Fast Track. Orphan Drug. Breakthrough Therapy.
• FCS is a rare genetic disorder that prevents the body from eliminating triglycerides and breaking down fats. As a result, patients will have higher levels of triglycerides, up to ten times higher than normal, causing pancreatitis, cardiovascular disease, deposits in the skin (xanthomas), and retinal fat deposits (lipemia retinalis). Acute and chronic pancreatitis are the most common cause for hospitalizations,4 leading to morbidity and mortality.
• FCS is very rare, but currently, it is estimated to affect 3,000 to 5,000 people globally, with a prevalence of 1 to 2 people per one million people; therefore, approximately 300 to 600 people in the U.S. have FCS. Ionis estimates that there are up to 3,000 Americans with FCS, stating the majority are undiagnosed.
• Supporting this approval is the phase III Balance trial, demonstrating a statically significant reduction in triglycerides at six months by 42.5% (p=0.0084) with continued improvement (57%) through 12 months vs. placebo. There was also a reduction in acute pancreatitis events, with only one event in the treatment arm vs. eleven events in the placebo group.
• The most common adverse events were low incidences of injection site reactions, decreased platelet counts, and arthralgia.
• The mainstay of FCS treatment is a low-fat diet. Current lipid-lowering therapies (HMG-CoA reductase inhibitors/statins, fibrates, omega-3 fatty acids, and niacin) do not have a mechanism of action to decrease chylomicrons in FCS and are, therefore, not very effective options.
• Tryngolzais is also being investigated in phase III studies for the treatment of patients with severe hypertriglyceridemia.
• Arrowhead Pharmaceuticals’ plozasiran is in phase III development for the treatment of FCS. It works by targeting ApoC-III utilizing the proprietary Targeted RNAi Molecule technology and is given as an SC dose every three months.