siRNA therapy shows long-term potential in lowering LDL-C

Novartis has announced that Leqvio^® (inclisiran), the first and only small interfering RNA (siRNA) therapy indicated to reduce low-density lipoprotein cholesterol (LDL-C), has demonstrated promising long-term results.

This is based on three-year follow up data from a Phase III trial, presented at the European Society of Cardiology (ESC) Congress 2023.

In the Phase III extension trial ORION-8, inclisiran in addition to statin therapy provided consistent LDL-C reduction beyond six years in patients with atherosclerotic cardiovascular disease (ASCVD), increased risk of ASCVD or heterozygous familial hypercholesterolemia (HeFH).

New data from the ORION-8 trial

ORION-8 is the largest clinical trial completed to date with inclisiran. It totalled an exposure of more than 8,500 patient-years during the trial’s three-year follow-up.

“In the largest study presented to date with several thousand injections, we can confirm that twice yearly dosing with the first-in-class siRNA therapy provides sustained reductions in LDL cholesterol by approximately 49 percent beyond six years of observation,” stated Dr Kausik Ray, Professor of Public Health at Imperial College London and Honorary Consultant Cardiologist at the Imperial College NHS Trust.

According to the data presented at the ESC Congress 2023, results from four previous completed Novartis trials (ORION-9, ORION-10, ORION-11 and ORION-3) showed that in patients who received inclisiran from every six months (after an initial dose and another at three months) for up to an additional three years, there were 78 percent of patients who attained their pre-specified LDL-C targets (<70mg/dL, the target for patients with ASCVD or <100mg/dL for patients with increased risk of ASCVD).

Potential of inclisiran for lowering LDL-C

These findings “reconfirm and extend prior observations about the safety profile and efficacy of inclisiran for people with ASCVD and those at risk of cardiovascular disease, in whom cholesterol levels are not adequately controlled,” Dr Ray explained.

Inclisiran is available on the NHS in England, as part of an agreement between NHS England and Novartis to pioneer a first-of-its-kind population health management approach to address elevated LDL-C in eligible patients with ASCVD.

Results from the ORION-8 study “reaffirm our partnership-based approach with the NHS… [and will help] contribute to reducing the considerable impact of CVD on the population,” declared Gerrit Zijlstra, Novartis Country Medical Head and Chief Medical Officer for Novartis UK.

Novartis gained global rights to develop, manufacture and commercialise inclisiran as part of a prior agreement with Alnylam Pharmaceuticals.

On 22 December 2021, Leqvio (inclisiran) was the first siRNA therapeutic to be approved to reduce LDL-C. This authorisation was granted by the US Food and Drug Administration (FDA).