Analysis of Inclisiran Show Effective, Sustained LDL-C Reduction in Patients with Atherosclerotic Cardiovascular Disease

Results from a pair of pooled post hoc analyses of the phase 3 ORION-9, -10, and -11 trials showed twice-yearly inclisiran (Leqvio, Novartis) provided effective and sustained low-density lipoprotein cholesterol (LDL-C) reduction in 2 sub-populations of patients with atherosclerotic cardiovascular disease (ASCVD): established cerebrovascular disease (CeVD) and polyvascular disease (PVD).

In the first study, patients with established CeVD treated with Leqvio achieved an average 55.2% reduction in LDL-C from baseline to day 510 compared with placebo. In the second study, patients with PVD treated with inclisiran achieved an average 48.9% reduction in LDL-C from baseline to day 510 compared with placebo. The results were similar for patients without PVD, who experienced an average 51.5% reduction in LDL-C from baseline to day 510 for inclisiran compared with placebo, according to a Novartis press release.

“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 3 ORION ASCVD population,” said David Soergel, MD, global head of cardiovascular, renal and metabolic drug development at Novartis, in the press release. “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.”

In both analyses, inclisiran was well-tolerated with a modest excess of mainly mild treatment-emergent adverse events at the injection site that were transient in nature, which is consistent with the results from the overall pooled population from the combined 1 to 3 trials. Treatment-emergent serious adverse events were reported more frequently in patients with PVD, which was likely due to their more advanced disease, according to the researchers.

Inclisiran is the first and only approved small interfering RNA LDL-C-lowering treatment in Europe and it is currently under review by the FDA and other health authorities, according to the press release.

REFERENCE

Novartis Leqvio®* (inclisiran) analyses show effective and sustained LDL-C reduction in two sub-populations of patients with ASCVD. Novartis. August 30, 2021. Accessed August 30, 2021. https://www.novartis.com/news/media-releases/novartis-leqvio-inclisiran-analyses-show-effective-and-sustained-ldl-c-reduction-two-sub-populations-patients-ascvd