Novartis announced results from a post-hoc analysis of pooled data from the Phase III ORION-10 and -11 trials evaluating the individual responses of patients on low-density lipoprotein cholesterol (LDL-C) reduction with inclisiran, a first-in-class investigational treatment for hyperlipidemia in adults. This new analysis of inclisiran showed a highly consistent effect, with a safety and tolerability profile similar to placebo, on a twice-yearly dosing schedule after an initial dose and one after three months, across individual patients with atherosclerotic cardiovascular disease (ASCVD) or risk equivalents over 17 months of treatment.

The analysis evaluated the efficacy and tolerability of inclisiran on top of a maximally tolerated dose of statins, in two studies of more than 2,300 patients (of which 1,164 were on inclisiran) from the Phase III trials. Results demonstrated a low inter-individual variability, with 99 per cent of inclisiran-treated patients showing a placebo-adjusted ≥30 per cent reduction of their LDL-C levels with a mean reduction of 54.1 per cent from baseline (observed values).

“This analysis confirms that as a small interfering RNA (siRNA), inclisiran provides a remarkably consistent treatment profile. Nearly all patients from these trials achieved clinically meaningful reductions of their LDL-C levels over the 17 month period, and inclisiran had a safety and tolerability profile similar to placebo. These efficacy and safety results showcase the promise of inclisiran as a therapy for those ASCVD patients who cannot reach their LDL-C goals,” said ORION-11 principal investigator Kausik Ray, Professor of Public Health, Consultant Cardiologist, Imperial College London. “

An LDL-C reduction of at least 50 per cent was reached by 88.4 per cent of patients at any time point in the study (observed values). After 17 months, 66.4 per cent of the inclisiran group had a reduction in LDL-C of at least 50 per cent as compared to 2.5 per cent from the placebo group (observed values). Overall, inclisiran was well-tolerated with a safety profile similar to placebo. All patients were on twice-yearly dosing, following an initial dose and one after three months.

“There remains an urgent need for innovative LDL-C-lowering therapies for patients not reaching their LDL-C target goals with the current standard of care. This analysis reinforced our view of inclisiran’s therapeutic value and its potential as the first cholesterol-lowering siRNA,” said David Soergel, Global Head of Cardiovascular, Renal and Metabolic Drug Development, Novartis. “With unique twice-yearly dosing, if approved, inclisiran may fit seamlessly into patients’ regular healthcare visits and help us reimagine treatment for ASCVD.”

Inclisiran is currently under review by the US Food and Drug Administration and the European Medicines Agency for the treatment of primary hyperlipidemia (including Heterozygous Familial Hypercholesterolemia) in adults who have elevated LDL-C while being on a maximally tolerated dose of statin therapy.