New long-term Leqvio data from ORION-8 study, presented at ESC congress, demonstrates consistent efficacy and safety beyond six years – Novartis

Novartis announced new long-term data from ORION-8, a Phase III open-label extension of ORION-9, ORION-10, ORION-11 and ORION-3 trials.

The data demonstrated that with twice-yearly dosing (after an initial dose and another at three months), Leqvio, in addition to statin therapy, provides consistent low-density lipoprotein cholesterol (LDL-C) reduction beyond six years in patients with atherosclerotic cardiovascular disease (ASCVD), increased risk of ASCVD or heterozygous familial hypercholesterolemia (HeFH). The results were presented in a late-breaking session at the European Society of Cardiology (ESC) Congress 2023 in Amsterdam.

ORION-8 , the largest clinical trial completed to date with Leqvio, continues to support the consistent long-term efficacy, safety, and tolerability of Leqvio, with a total exposure of more than 8,500 patient-years during the trial’s three-year follow-up. Patients from four previous completed Novartis trials (ORION-9, ORION-10, ORION-11 and ORION-3) received Leqvio every six months for up to an additional three years. Nearly 80% (78.4% (95% CI: 76.8, 80.0)) of patients reached their pre-specified LDL-C targets, and on average, LDL-C levels were reduced by approximately 50% (49.4% (95% CI: 48.3, 50.4)). These results demonstrate consistent efficacy as they are comparable to the LDL-C reductions observed at the end of the initial trials. In addition, the long-term safety data was consistent with previous findings, confirming the well-established and favorable safety profile of Leqvio1.

“These long-term results show that twice-yearly inclisiran, when used in addition to statin therapy, provides consistent LDL-C reduction in patients with ASCVD, and those at increased risk of developing cardiovascular disease,” said Norman Lepor, M.D., a Los Angeles based cardiologist and Director of the National Heart Institute. “While LDL-C is one of the most readily modifiable risk factors for heart disease, many patients do not reach their recommended LDL-C target through use of statin therapy alone. The demonstrated long-term efficacy of inclisiran indicates that after administration by a health care provider (HCP), both patient and HCP can be confident that a dose has been received for six months.”

ORION-8 is part of VictORION, a large dynamic clinical trial program co-created with healthcare partners worldwide to generate evidence on the impact of cholesterol-lowering with Leqvio. The program is enrolling over 60,000 patients, across more than 50 countries and more than 30 clinical trials.

“The ORION-8 results affirm the benefits of Leqvio in helping patients achieve sustained LDL-C reduction, which is important as cumulative exposure to LDL-C leads to the growth of plaque in the arteries and an increased risk of cardiovascular events,” said David Soergel, M.D., Global Head of Cardiovascular, Renal and Metabolic Drug Development, Novartis. “The trial is part of a growing body of evidence for Leqvio being generated through our ongoing VictORION program that is examining the use of Leqvio in broad and varied patient populations affected by ASCVD.”

Leqvio is the first and only small interfering RNA (siRNA) therapy to lower LDL-C. It is approved in over 80 countries, including the US, EU and China. In the US, the FDA approved a label update in July 2023 that allows for earlier use of Leqvio to help reduce LDL-C as an adjunct to diet and statin therapy for patients with elevated LDL-C who have not had a cardiovascular event but are at an increased risk of heart disease.

About ORION-8 ORION-8 (NCT03814187) is a three-year open-label extension of the placebo-controlled 18-month Phase III trials ORION-9, ORION-10, and ORION-11 and the four-year Phase II ORION-3 trial (an extension of the one-year Phase II ORION-1 trial). ORION-8 evaluated the long-term safety, efficacy and tolerability of Leqvio in 3,274 patients with atherosclerotic cardiovascular disease (ASCVD), increased risk of ASCVD (includes patients who have comorbidities such as diabetes and hypertension) or heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C), despite maximum tolerated dose of LDL-C lowering therapies. 2,446 patients completed the trial to Day 1080 (three years). The primary endpoint of the study was the proportion of patients achieving pre-specified LDL-C targets at the end of the study, either Day 1080 or 90 days after the last injection5. Patients received 300 mg inclisiran sodium twice yearly (every six months) for up to an additional three years after baseline studies. Adverse events at the injection site occurred in 5.9% of patients, compared with 8% in the Leqvio arm of the pooled analysis of ORION-9, ORION-10, and ORION-11 trials.