Pooled ORION Analysis Details Inclisiran Effect on LDL-C in ASCVD Patients

Results of a pooled analysis of trials from the ORION program offer further insight into the effects of inclisiran on LDL-C in patients with atherosclerotic cardiovascular disease.

This article was originally published online by Practical Cardiology's sibling publication, HCPLive.com.

New pooled data from a trio of pivotal phase 3 trials assessing novel investigative drug inclisiran, which were presented at ACC 20, demonstrate Novartis's first-in-class siRNA drug inclisiran provided significant and durable benefit for LDL cholesterol (LDL-C) reduction in patients with atherosclerotic cardiovascular disease (ASCVD).

The ORION trial program now includes new data pooled from ORION-9, -10, and -11 showing reduction in LDL-C of 51% when used in addition to other lipid-lowering therapies (LLT) over 17 months of treatment.

A prespecified exploratory analysis using safety from the 3 trials also indicated fewer major adverse cardiovascular events (MACE) with inclisiran (7.1%) versus placebo (9.4%).

Patients treated with inclisiran also reported good tolerance, with a safety profile similar to placebo. The most common adverse reactions reported to occur in ≥3% of treated patients and more frequently than those with placebo included: diabetes mellitus; hypertension; nasopharyngitis; arthralgia; back pain; dyspnea; bronchitis; and upper respiratory tract infection.

The novel, first-in-class drug is initially administered subcutaneously, again at 3 months, and then again every 6 months. It has potential to become the first and only LDL-C-lowering treatment in the siRNA class marketed for use in the US.

In a special edition DocTalk podcast interview with HCPLive®—Practical Cardiology's sibling publication—ORION-11 principal investigator Kausik Ray, MD, of the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, discussed the newest inclisiran findings, what the marketed potential of the therapy is as it has been currently assessed, and what future research will entail.

Ray also shared planned to assess the therapy’s benefit for pediatric patients, homozygous familial hypercholesterolemia (HoFH) benefits, and the reduction of cardiovascular outcome risks. These, plus a currently-planned extension trial, will take the ORION program research into 2024.

“All these patients in ORION-9, -10, and -11 will now go into to an open-label extension program,” Ray said. “And that’s ORION-8, and that will report out in several years’ time.”