Pooled pivotal phase 3 trial data from the ORION program shows the first-in-class therapy's significant benefit and tolerability versus placebo.
Kausik Ray, MD
New pooled data from a trio of pivotal phase 3 trials assessing novel investigative drug inclisiran, presented virtually at the ACC.20 Together with Word Congress of Cardiology (ACC/WCC) Scientific Sessions this Saturday show the first-in-class siRNA drug’s 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®, 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.”
The therapy is currently under US Food and Drug Administration (FDA) review for use in adults with ASCVD or heterozygous familial hypercholesterolemia (HeFH) who have elevated LDL-C while being on a maximum tolerated dose of an LLT.