Novartis announced results from the Phase II open-label extension ORION-3 trial, which showed that Leqvio provides effective low-density lipoprotein cholesterol (LDL-C) reduction over a four-year period in patients with either atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalent, and elevated LDL-C despite maximally tolerated statin therapy.
Leqvio is the first and only small interfering RNA (siRNA) therapy to lower LDL-C and is administered with two doses a year. Results were presented at the American Heart Association (AHA) Scientific Sessions 2022.
“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.
“The ORION-3 results show that Leqvio consistently helped patients lower their LDL-C, and with a well-tolerated safety profile,” said David Soergel, M.D., Global Head of Cardiovascular, Renal and Metabolic Drug Development, Novartis. “With two maintenance doses a year, Leqvio is an important option for ASCVD patients who are not reaching recommended LDL-C target levels despite taking other cholesterol-lowering medications.”
