Novartis’ Phase III clinical trials for inclisiran, an investigational first-in-class siRNA cholesterol-lowering therapy, have met their primary endpoints of durable and potent LDL-C reductions versus placebo.
Inclisiran is a potential small interfering RNA (siRNA) investigational agent used to treat hyperlipidemia in adults.
ORION-9, the first pivotal Phase III, placebo-controlled, double-blind, randomised study evaluated the efficacy, safety and tolerability of 300mg inclisiran sodium in 482 patients with clinical or genetic evidence of heterozygous familial hypercholesterolemia (HeFH).
The study administrated the drug in two starter doses and then every six months.
In ORION-10, 300mg of inclisiran sodium was administered in an initial dose, again at three months, and then every six months in 1,561 participants with ASCVD and elevated LDL-C.
The Phase III, placebo-controlled, double-blind, randomised ORION-11 study also evaluated the efficacy, safety, and tolerability of 300mg inclisiran sodium in 1,617 patients. The international study was conducted at 70 sites in seven countries.
In all three studies, the drug was found to be well-tolerated with a safety profile similar to placebo.
ORION-11 principal investigator Kausik Ray said: “Inclisiran and its twice-yearly dosing schedule in three large trials consistently delivered potent and sustained cholesterol-lowering and was generally well tolerated.
“These data provide support for this groundbreaking approach to reducing LDL-C in patients who are not achieving LDL-C treatment goals with the current standard of care.”
The most common adverse reactions reported during the trials were diabetes mellitus, hypertension, nasopharyngitis, arthralgia, back pain, dypspnea, bronchitis and upper respiratory tract infection.
Adverse events at the injection site were noted to be more frequent with inclisiran than placebo and were generally mild. None were severe or persistent.
Hyperlipidemia refers to the high level of lipids, such as Low Density Lipoprotein Cholesterol (LDL-C). Elevated LDL-C levels can lead to ASCVD, which may cause cardiovascular event such as a heart attack or stroke.