Meta-Analysis of Inclisiran for the Treatment of Hypercholesterolemia

Khan, Sajjad; Naz, Arshi; Masood, Muhammad Qamar; Shah, Rahman

doi:10.1016/j.amjcard.2020.08.018

Cited by 80 publications

(72 citation statements)

References 18 publications

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“…Inclisiran administered as a subcutaneous injection was generally safe and well tolerated as a lipid lowering therapy in clinical trials, showing a safety profile comparable to that of placebo [ 6 , 7 , 12 , 16 , 17 , 20 , 21 ]. In the pivotal phase III clinical trials (ORION-9, ORION-10 and ORION-11), adverse reactions at the injection site were the only adverse reactions associated with inclisiran (occurring in 8.2% of inclisiran recipients versus 1.8% of placebo recipients) [ 3 ].…”

Section: Scientific Summarymentioning

confidence: 99%

Inclisiran: First Approval

Lamb

2021

Drugs

232

190

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Inclisiran (Leqvio ® ; Novartis) is a first-in-class, cholesterol-lowering small interfering RNA (siRNA) conjugated to triantennary N-acetylgalactosamine carbohydrates (GalNAc). Inclisiran received its first approval in December 2020 in the EU for use in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet. It is intended for use in combination with a statin or a statin with other lipid-lowering therapies in patients unable to reach low-density lipoprotein cholesterol goals with the maximum tolerated statin dose. In patients who are statin-intolerant or for whom a statin is contraindicated, inclisiran can be used alone or in combination with other lipid-lowering therapies. Inclisiran is administered as a twice-yearly subcutaneous injection. This article summarizes the milestones in the development of inclisiran leading to this first approval for primary hypercholesterolaemia or mixed dyslipidaemia.

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Section: Scientific Summarymentioning

confidence: 99%

Inclisiran: First Approval

Lamb

2021

Drugs

232

190

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“…The analysis confirms that LDL cholesterol is decreased 51% compared to the placebo group [ 18 ]. In addition, decrease in total cholesterol was 37%, apolipoprotein B 41%, and non-HDL-C 45% [ 18 ]. Overall, these decreases were associated with a 24% decrease in cardiovascular events, such as cardiac death, cardiac arrest, myocardial infarction, or stroke.…”

Section: Introductionmentioning

confidence: 54%

“…In all of these above-mentioned studies, 300 mg doses of inclisiran sodium (or corresponding 284 mg of inclisiran free acid) on days 1, 90, 270 and 450 were used as subcutaneous 1.5 mL injections. A recent meta-analysis concerning these three studies has summarized the main results [ 18 ]. The analysis confirms that LDL cholesterol is decreased 51% compared to the placebo group [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…A recent meta-analysis concerning these three studies has summarized the main results [ 18 ]. The analysis confirms that LDL cholesterol is decreased 51% compared to the placebo group [ 18 ]. In addition, decrease in total cholesterol was 37%, apolipoprotein B 41%, and non-HDL-C 45% [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, no serious adverse effects were reported in these three trials, but some mild injection site reactions occurred [ 18 ]. A recent publication from phase 1 ORION-1 trial shows that inclisiran does not exert adverse effects on platelet counts, and has no effect on lymphocyte, monocyte, or neutrophil counts at day 180 [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Novel RNAi-Based Therapies for Atherosclerosis

Ruotsalainen

Mäkinen

Ylä‐Herttuala

2021

Curr Atheroscler Rep

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Purpose of Review Atherosclerosis, defined by inflammation and accumulation of cholesterol, extracellular matrix, and cell debris into the arteries is a common factor behind cardiovascular diseases (CVD), such as coronary artery disease, peripheral artery disease, and stroke. In this review, we discuss and describe novel RNA interference (RNAi)-based therapies in clinical trials and on the market. Recent Findings The first RNAi-based therapies have entered clinical use for the control of atherosclerosis risk factors, i.e., blood cholesterol levels. The most advanced treatment is silencing of proprotein convertase subtilisin/kexin type 9 (PCSK9) with a drug called inclisiran, which has been approved for the treatment of hypercholesterolemia in late 2020, and results in a robust decrease in plasma cholesterol levels. Summary As the new RNAi therapies for atherosclerosis are now entering markets, the usefulness of these therapies will be further evaluated in larger patient cohorts. Thus, it remains to be seen how fast, effectively and eminently these new drugs consolidate their niche within the cardiovascular disease drug palette.

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