New long-term Leqvio Phase II ORION-3 trial data show sustained efficacy and safety low-density lipoprotein cholesterol (LDL-C) reduction over four years

Results were presented at the American Heart Association (AHA) Scientific Sessions 20221.

“The results we’ve seen in patients after four years of treatment demonstrate that inclisiran is well-tolerated and can help patients achieve LDL-C reduction while also maintaining and sustaining their levels,” said Kausik Ray, M.D., Professor of Public Health in the Department of Public Health and Primary Care at Imperial College London and Honorary Consultant Cardiologist at the Imperial College NHS Trust. “Still too many patients are struggling to reach their LDL-C target levels. A therapy that provides sustained LDL-C reduction with a twice-yearly maintenance dosing schedule may be a turning point in the treatment of ASCVD.”

In ORION-3, an open-label extension of the Phase II ORION-1 trial, LDL-C level reduction was sustained over the four-year study period: patients treated with Leqvio achieved an average 47.5% reduction in LDL-C from baseline (Day 1 of ORION-1) to Day 210 (95% Cl:-50.69,-44.27) and a time-averaged reduction in LDL-C of 44.2% over the four years through twice-yearly dosing.

“Patients with ASCVD are a large, high-risk population in the US, and a majority are not achieving their LDL-C target levels,” said Norman Lepor, M.D., a Los Angeles based cardiologist and Director of the National Heart Institute. “The sustained benefit of a twice-yearly treatment is a major advance in meeting the needs of these patients.”

ORION-3 provides the longest safety follow-up in a Leqvio study to date. After four years of therapy, Leqvio was well-tolerated, with a safety profile consistent with previous 18-month Phase III LDL-C lowering studies The most common drug-related treatment-emergent adverse events were general disorders and injection site reactions that were mostly mild-to ­moderate, consistent with previous studies

In addition to this ORION-3 data presented at the AHA Scientific Sessions, there was a pooled exploratory safety analysis of the Phase III ORION trials entitled, “Inclisiran and cardiovascular events: a patient-level analysis of Phase III trials” published in the European Heart Journal on November 4, adding to the growing body of safety evidence for Leqvio.

About ORION-3: ORION-3 (NCT03060577) is an open-label, non-randomized, extension of the Phase II ORION-1 trial which evaluated Leqvio the long-term safety and efficacy of Leqvio in 233 patients with ASCVD (~1210 patient years), ASCVD risk equivalents, and elevated LDL-C despite maximally tolerated lipid-lowering therapy. The primary endpoint of the study was percentage LDL-C change from baseline (Day 1 of ORION-1) to day 210 of ORION-3. LDL-C levels were assessed up to Day 1440 (4 years). Patients received twice-yearly doses of 300 mg inclisiran sodium in this study.

About VictORION: Novartis envisions a world where ASCVD is eliminated so patients can live longer and healthier lives. ORION-3 is part of VictORION, an innovative and robust clinical program for Leqvio, comprising 27 trials and enrolling 47,000 patients in more than 50 countries worldwide. The program is designed to expand on the foundational evidence of LDL-C reduction with Leqvio in diverse patient populations to include implementation research, real-world evidence, and trials that establish its benefits on cardiovascular outcomes. A growing number of studies are planned to generate a vast array of data with major trials such as ORION-4, V (VictORION)-2-PREVENT, V-INITIATE, V-INCEPTION, V-REAL, V-DIFFERENCE, and V-PLAQUE. The VictORION program reinforces our commitment to stopping premature death from cardiovascular disease and to leading a generational decline in cardiovascular morbidity and mortality.