Ionis Pharmaceuticals has shared positive results from a late-stage study of olezarsen in adults with familial chylomicronaemia syndrome (FCS), a rare genetic disease estimated to affect up to 13 people per million in the US.
Due to impaired function of the enzyme lipoprotein lipase, patients with FCS cannot effectively break down fats consumed through the diet, or triglycerides (TGs), and are at a high risk of acute pancreatitis and other chronic health issues.
There are no FDA-approved therapies for FCS, with Ionis outlining that standard TG-lowering therapies are generally ineffective in this indication and that patients currently rely solely on nutrition management through extremely restrictive diets to navigate the health risks associated with the disease.
Olezarsen is an RNA-targeted investigational ligand-conjugated antisense medicine designed to inhibit the body’s production of apoC-III, a protein produced in the liver that regulates TG metabolism in the blood.
Full results from the phase 3 Balance trial, which randomised patients to receive olezarsen 80mg, 50mg or placebo once every four weeks, were presented at this year’s American College of Cardiology Annual Meeting and published in the New England Journal of Medicine.
In the study’s higher dose group, olezarsen demonstrated statistically significant placebo-adjusted reductions in TG levels of 44% from baseline to six months and 59% from six to 12 months. Ionis added that apoC-III placebo-adjusted reductions were robust and sustained at six and 12 months, at 75% and 81%, respectively.
Olezarsen also reduced TG levels in the 50mg group, but this difference was not statistically significant at six months compared to placebo. Reductions from six to 12 months did improve, however, with olezarsen 50mg achieving a placebo-adjusted 44% reduction in TGs.
Patients treated with olezarsen had markedly fewer acute pancreatitis events during the 12-month period compared to placebo and experienced a placebo-adjusted 84% reduction in all-cause hospitalisations between baseline and 12 months.
Brett Monia, chief executive officer of Ionis, said: “Balance is the first clinical study to validate the association of reduced TG levels with reduced incidence of acute pancreatitis events in patients with severely elevated TGs.
“This important finding supports the potential for olezarsen to be the standard of care for patients with FCS, if approved.”
Olezarsen has already been granted fast track designation, orphan drug designation and breakthrough therapy designation by the US Food and Drug Administration for the treatment of FCS. Beyond this patient population, Ionis is evaluating the drug in phase 3 trials as a treatment for severe hypertriglyceridaemia.