EMA Committee Backs Tryngolza for Rare Lipid Disorder

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended granting marketing authorization in the European Union to Tryngolza (olezarsen; Ionis Ireland Limited) for treating adults with familial chylomicronemia syndrome (FCS).

The drug, to be available as an 80-mg solution for injection in prefilled pens, will be used as an adjunct to dietary modifications in adult patients with genetically confirmed FCS.

FCS is a rare inherited disorder caused by loss-of-function variants in LPL or related genes, leading to absent or severely reduced lipoprotein lipase activity. This results in extreme hypertriglyceridemia (often > 880 mg/dL or 10 mmol/L) due to accumulation of chylomicrons and very low-density lipoprotein (VLDL). 

FCS affects about 13 people per million in Europe and causes recurrent acute pancreatitis (in about 85% of patients), severe abdominal pain, and chronic complications. Standard lipid-lowering therapies are typically ineffective, and strict fat-restricted diets are difficult to maintain, making disease management challenging.

Tryngolza, a lipid-modifying agent, is an antisense oligonucleotide-GalNAc₃ carbohydrate ligand conjugate that targets apolipoprotein C-III (apoC-III) mRNA in hepatocytes. The GalNAc₃ moiety facilitates selective uptake by liver cells and, once internalized, the antisense oligonucleotide blocks apoC-III protein synthesis. This enhances lipolysis and hepatic clearance of triglyceride-rich lipoproteins, including VLDL and chylomicrons, ultimately lowering plasma triglyceride levels.

Significant Benefits in Clinical Trials

The CHMP decision relied on positive findings from the phase 3 Balance trial involving 66 patients with genetically confirmed FCS and severe hypertriglyceridemia, including 71% with a history of acute pancreatitis. Participants were randomly assigned to receive Tryngolza 80 mg, 50 mg, or placebo subcutaneous injections every 4 weeks for 49 weeks. Tryngolza 80 mg significantly reduced triglyceride levels by 43.5 percentage points at 6 months compared with placebo, while the 50-mg dose showed a nonsignificant reduction. 

Both doses markedly decreased apoC-III concentrations, with the 80-mg group achieving a 73.7-percentage point drop and the 50-mg group a 65.5-percentage point decline vs placebo. Acute pancreatitis events decreased significantly, with 11 episodes occurring among placebo recipients compared with just one in each Tryngolza group over 53 weeks, indicating an 88% risk reduction. 

The most common side effects of Tryngolza include injection-site erythema, headache, arthralgia, and vomiting.