Study Shows Consistent Efficacy, Safety of Inclisiran in Lowering Low-Density Lipoprotein Cholesterol

An analysis of phase 3 study data found that 99% of patients who received inclisiran showed a significant placebo-adjusted reduction in low-density lipoprotein cholesterol (LDL-C).

Inclisiran is an investigational cholesterol-lowering treatment that could potentially be the first LDL-C-lowering small-interfering RNA treatment on the market. It is administered as a subcutaneous injection with the first 2 doses given 3 months apart, followed by a follow-up injection every 6 months after that.

The new analysis pooled data from the ORION-10 and ORION-11 trials, both of which were phase 3, placebo-controlled, double-blind, randomized studies. They included more than 2300 total patients, 1164 of whom received inclisiran. The analysis, presented at the 2020 Congress of the European Society of Cardiology, evaluated the efficacy and tolerability of inclisiran in addition to a maximally tolerated dose of statins.

The analysis showed that 99% of inclisiran-treated patients showed a placebo-adjusted reduction in LDL-C of 30% or more, with a mean reduction of 54.1% from baseline, according to the study. A reduction of at least 50% was reached by 88.4% of patients at any time during the study. Furthermore, after 17 months, 66.4% of the inclisiran group had a reduction of at least 50%, compared with 2.5% of those in the placebo group.

“This analysis confirms that as a small interfering RNA, inclisiran provides a remarkably consistent treatment profile,” said ORION-11 principal investigator Kausik Ray, MD, in a press release. “Nearly all patients from these trials achieved clinically meaningfully reductions of their LDL-C levels over the 17-month period, and inclisiran had a safety and tolerability profile similar to placebo.”

In the trials, the most common adverse events (AEs) were diabetes mellitus, hypertension, nasopharyngitis, arthralgia, back pain, dyspnea, bronchitis, and upper respiratory tract infection. The authors noted that AEs at the injection site were more frequent with inclisiran than placebo and were generally mild. None were severe or persistent.

“There remains an urgent need for innovative LDL-C-lowering therapies for patients not reaching their LDL-C target goals with current standard of care,” said David Soergel, MD, global head of cardiovascular, renal, and metabolic drug development at Novartis, in a press release. “This analysis reinforced our view of inclisarin’s therapeutic value and its potential as the first cholesterol-lowering siRNA. With a unique twice-yearly dosing, if approved, inclisiran may fit seamlessly into patients’ regular health care visits and help us reimagine treatment for [atherosclerotic cardiovascular disease].”

REFERENCE

Novartis new analysis shows high consistency in lowering LDL-C in individual response with investigational inclisiran [news release]. PR Newswire; August 30, 2020. https://www.prnewswire.com/news-releases/novartis-new-analysis-shows-high-consistency-in-lowering-ldl-c-in-individual-response-with-investigational-inclisiran-301120583.html. Accessed August 31, 2020.