Instant Report
FDF

Date: 31-Aug-2021

Novartis Phase III ORION Leqvio Analyses Show Effective And Sustained LDL-C Reduction In Two Sub-populations Of Patients With ASCVD

Novartis announced results from two pooled post hoc analyses of phase III ORION-9, -10 and -11 trials that showed twice-yearly Leqvio (inclisiran) provided effective and sustained low-density lipoprotein cholesterol (LDL-C) reduction in two sub-populations of atherosclerotic cardiovascular disease (ASCVD) – established cerebrovascular disease (CeVD) and polyvascular disease (PVD). Results were presented at the ESC Congress 2021, organized by the European Society of Cardiology (ESC).

In the first analysis, patients with established CeVD treated with Leqvio achieved an average 55.2% reduction in LDL-C from baseline to Day 510 compared with placebo (P<.0001). In the second analysis, patients with PVD treated with Leqvio achieved an average 48.9% reduction in LDL-C from baseline to Day 510 compared with placebo (P<.0001). Results were similar for patients without PVD, with an average 51.5% reduction in LDL-C from baseline to Day 510 for Leqvio compared with placebo (P<.0001).

“We know that long-term exposure to persistently elevated LDL-C increases the risk of ASCVD, which may lead to cardiovascular events such as heart attack or stroke. These analyses show that twice-yearly Leqvio provides similar effective and sustained LDL-C reduction in two smaller ASCVD sub-populations – CeVD and PVD – as in the wider Phase III ORION ASCVD population,” said David Soergel, M.D., global head of cardiovascular, renal and metabolic drug development, Novartis. “As the first and only small interfering RNA to provide effective and sustained LDL-C reduction, Leqvio helps manage a critical cardiovascular risk factor for ASCVD. It is a key component of our ambition to bend the curve of life by reducing and stopping premature death from cardiovascular disease.”

Leqvio was well-tolerated in both analyses, with a modest excess of mainly mild treatment-emergent adverse events (TEAEs) at the injection site that were transient in nature, which is consistent with the results from the overall pooled population from the combined trials. Treatment-emergent serious adverse events (TESAEs) were reported more frequently in patients with PVD, which was likely due to their more advanced disease.

Leqvio is the first and only approved small interfering RNA (siRNA) LDL-C-lowering treatment in Europe. It is currently under review by the US Food and Drug Administration (FDA) and other health authorities.

The pooled analyses include data from the Leqvio ORION-9, -10 and -11 trials, which were multicenter, double-blind, randomized, placebo-controlled,18-month (540-day) studies evaluating Leqvio in 3,655 patients with heterozygous familial hypercholesterolemia (ORION-9), atherosclerotic cardiovascular disease (ASCVD) (ORION-10), and ASCVD or ASCVD risk equivalents (ORION-11) on statin therapy who required additional low-density lipoprotein cholesterol (LDL-C) lowering. The primary endpoints for these studies were percentage change in LDL-C from baseline to Day 510 and time-adjusted percentage change in LDL-C from baseline between Day 90 and up to Day 540. The primary endpoints were achieved in all three studies. Safety was assessed over 540 days.

The established cerebrovascular disease (CeVD) post hoc analysis included 202 patients with established CeVD, of which 110 received Leqvio and 92 received placebo1. Patients with established CeVD had prior ischemic stroke, and/or carotid artery narrowing (by angiography or ultrasound) of more than 70%, and/or prior percutaneous or surgical carotid artery revascularization.

The polyvascular disease (PVD) post hoc analysis included 470 patients with PVD, of which 228 received Leqvio and 242 received placebo. Patients with PVD had ASCVD in at least two of the major vascular artery territories: coronary, cerebrovascular and/or peripheral.

ORION-9 was a pivotal phase III, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of Leqvio sodium salt 300 mg, equivalent to 284 mg of Leqvio, administered subcutaneously by a healthcare professional. Starting with an initial dose, Leqvio was then administered again at three months and then every six months thereafter in 482 participants with clinical or genetic evidence of heterozygous familial hypercholesterolemia and elevated LDL-C, despite a maximally tolerated dose of LDL-C-lowering therapies (e.g., a statin or ezetimibe). For the primary endpoints of ORION-9, Leqvio delivered mean placebo-adjusted percentage change in LDL-C reductions of 48% (P<.0001) at 510 days and demonstrated time-adjusted percentage change in LDL-C reductions of 44% (P<.0001) from 90 through 540 days. The international study was conducted at 46 sites in eight countries.

ORION-10 was a pivotal phase III, placebo-controlled, double-blind, randomized study to evaluate the efficacy, safety and tolerability of Leqvio sodium salt 300 mg, equivalent to 284 mg of Leqvio, administered subcutaneously by a healthcare professional. Starting with an initial dose, Leqvio was then administered again at three months and then every six months thereafter in 1,561 participants with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C, despite a maximally tolerated dose of LDL-C-lowering therapies (e.g., a statin and/or ezetimibe). For the primary endpoints of ORION-10, Leqvio delivered mean placebo-adjusted percentage change in LDL-C reductions of 52% (P<.0001) at 510 days and demonstrated time-adjusted percentage change in LDL-C reductions of 54% (P<.0001) from 90 through 540 days. The study was conducted at 145 sites in the United States.