On January 31, Ionis Pharmaceuticals announced it received fast track designation from the FDA for its investigational therapy, olezarsen, in patients with familial chylomicronemia syndrome (FCS). Olezarsen is also being investigated in a Phase III clinical trial (NCT05079919) for severe hypertriglyceridemia (sHTG) in the US and several European countries, including France, Germany, Italy, and the UK. According to GlobalData, this decision from the FDA has pushed the likelihood of approval of olezarsen for sHTG to 72%. If approved, olezarsen has potential to fulfill an unmet need of more effective triglyceride lipid-lowering therapies.
The incidence of sHTG is rising globally, and according to GlobalData epidemiologists, the US alone will reach over 17 million prevalent cases by 2025. sHTG often occurs secondary to FCS, but also results from environmental factors including high-fat diets and sedentary lifestyles. In sHTG, triglyceride levels are greatly elevated (>500mg/dL), increasing the risk of atherosclerotic cardiovascular disease and death. In the blood, apolipoprotein CII (apoCII) inhibits lipoprotein lipase, an enzyme responsible for the breakdown of triglycerides and clearance of triglyceride-rich lipoproteins. Olezarsen is an antisense RNA oligonucleotide that inhibits the hepatic production of apoCII, thus enhancing clearance and decreasing triglyceride serum levels, and decreasing atherosclerotic risk.
Waylivra (volanesorsen) is another apoCII inhibitor marketed by Ionis in the EU for patients with FCS with an inadequate response to other TG-lipid-lowering therapies, including statins and ezetimibe. The FDA rejected Waylivra’s approval for FCS in the US in 2018, making this fast track designation for olezarsen in FCS a big win for Ionis. Both Waylivra and olezarsen are being investigated in sHTG, and if Phase III clinical trials prove successful, GlobalData predicts Waylivra and olezarsen could launch for sHTG patients as early as 2028 in the US and Europe. This additional approval of Waylivra and olezarsen for sHTG will further bolster Ionis’s dyslipidemia portfolio and strengthen its competitive standing in the dyslipidemia space.