Triglyceride Levels Substantially Reduced With Olezarsen Compared To Placebo

Olezarsen decreased levels of triglycerides compared pinch placebo successful patients pinch mean hypertriglyceridemia and elevated cardiovascular risk, according to a late-breaking proceedings presented successful a Hot Line convention coming astatine ESC Congress 2025 and simultaneously published successful New England Journal of Medicine.

High levels of triglycerides are an important consequence facet for atherosclerotic cardiovascular illness (ASCVD) and yet nan effects of existent therapies are modest. Olezarsen targets nan mRNA of apolipoprotein C-III, which inhibits triglyceride clearance. Olezarsen has been shown to little triglyceride levels successful mini shape II tests and successful patients pinch very precocious triglyceride levels. We investigated nan efficacy and information of olezarsen successful patients pinch mean hypertriglyceridemia astatine precocious ASCVD consequence successful nan ESSENCE-TIMI 73b trial."

Doctor Brian Bergmark, Principal Investigator, from nan TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, USA

The placebo-controlled, double-blind shape III ESSENCE-TIMI 73b proceedings was conducted astatine 160 sites successful North America and Europe. The proceedings included big patients pinch mean hypertriglyceridemia (triglycerides 150−499 mg/dL) and elevated cardiovascular consequence owed to an established test of ASCVD aliases accrued ASCVD consequence arsenic a consequence of type 2 glucosuria mellitus and property ≥55 years. Patients were expected to beryllium connected optimised unchangeable low-density lipoprotein-cholesterol (LDL-C)-lowering therapy astatine enrolment. The ESSENCE-TIMI 73b proceedings besides included patients pinch terrible hypertriglyceridemia (triglycerides ≥500 mg/dL). The superior analytic cohort was patients pinch mean hypertriglyceridemia arsenic patients pinch terrible hypertriglyceridemia are being studied successful dedicated, abstracted trials.

The superior study organization included 1,349 patients pinch mean hypertriglyceridemia and elevated cardiovascular consequence who were randomised to olezarsen 50 mg (n=254), olezarsen 80 mg (n=766) aliases placebo (n=329) fixed each 4 weeks via subcutaneous injection for 12 months. The superior endpoint was nan percent alteration from baseline successful triglyceride levels astatine 6 months compared pinch placebo.

The superior study organization had a median property of 64 years and 40% were women. The median triglyceride level astatine baseline was 238.5 mg/dL.

At 6 months, olezarsen importantly reduced levels of triglycerides: nan placebo-adjusted least-squares mean quality successful percent alteration from baseline was −58.4 percent points for olezarsen 50 mg and −60.6 percent points for olezarsen 80 mg (both p<0.001 vs. placebo).

In nan placebo group, 12.5% of patients had triglyceride levels <150 mg/dL astatine 6 months, compared pinch 85.0% of patients connected olezarsen 50 mg and 88.7% connected olezarsen 80 mg (p<0.001 for both). At 12 months, nan proportions were 20.6%, 82.8% and 85.0% for placebo, olezarsen 50 mg and olezarsen 80 mg, respectively (p<0.001 for some vs. placebo). Olezarsen importantly reduced levels of different lipoproteins − remnant cholesterol, non-high-density lipoprotein cholesterin and apolipoprotein B - pinch nary important effect connected LDL-C.

The incidence of superior adverse events appeared similar: 9% pinch olezarsen 50 mg, 14% pinch olezarsen 80 mg and 11% pinch placebo. Liver transaminase elevations to immoderate grade supra nan precocious limit of nan normal scope were much communal pinch olezarsen 50 mg (34.2%) and olezarsen 80 mg (38.3%) than pinch placebo (17.6%) (both p<0.001); however, clinically meaningful increases were uncommon and akin crossed groups.

Summarising, Doctor Bergmark said: "In a organization pinch mean hypertriglyceridemia and elevated cardiovascular risk, monthly olezarsen resulted successful important triglyceride lowering greater than would beryllium expected from presently disposable therapies, pinch much than 80% of patients treated pinch olezarsen achieving normal triglyceride levels."