Novartis’ First-in-Class siRNA Cholesterol-Lowering Drug Leqvio (Inclisiran) Demonstrates Significant and Sustained LDL-C Reduction in Patients with Obesity Regardless of BMI

News on November 14, 2021 /BioValleyBIOON/ --Novartis(Novartis) recently at the 2021 American Heart Association (AHA) ScientificMeetingThe aggregated post-hoc analysis results of the Phase 3 ORION-9, -10, and -11 trials for the cholesterol-lowering innovative drug Leqvio (inclisiran) were published, exploring the impact of Body Mass Index (BMI) levels on the efficacy and safety of twice-yearly Leqvio treatment. The data shows:In patients of all BMI types, when used in combination with other lipid-lowering drugs, Leqvio showed good tolerability and effectively and continuously reduced LDL-C levels by approximately 50% compared to placebo at the 17th month of treatment.

These trials enrolled patients with atherosclerotic cardiovascular disease (ASCVD), heterozygous familial hypercholesterolemia (HeFH), and adults with ASCVD risk equivalents.Regardless of BMI, Leqvio demonstrated effective and sustained lipid-lowering effects across a range of atherogenic lipids compared to placebo, indicating that its pharmacology does not seem to be affected by excess weight.In addition to reducing LDL-C levels by approximately 50%,It also reduced triglycerides (~10%), total cholesterol (~33%), non-HDL-C (~45%), and apolipoprotein B (~40%).Leqvio'sTolerability was similar to placebo.。Placebo group and Leqvio groupSevere adverse events increase with the increase of BMI levels.TEAEs at the injection site were more common in the Leqvio group but were all mild or moderate. The impact of Leqvio on the incidence and mortality of cardiovascular disease has not been determined.

Lawrence A. Leiter, Deputy Director of the Center for Clinical Nutrition and Risk Factor Modification at St. Michael's Hospital in Toronto, Canada, stated: "For vascular disease patients with a higher BMI, doctors usually recommend taking cholesterol-lowering medications as well asWeight Loss。Despite our best efforts, butWeight Loss"Not always achievable. BMI analysis reveals the potential of Leqvio in helping patients reduce LDL-C, regardless of their weight, with only two doses required per year."

Leqvio (inclisiran) is a first-of-its-kindsiRNACholesterol-lowering drug, developed by The Medicines Company (TMC).NovartisIn November 2019, it acquired TMC for $9.4 billion, bringing inclisiran into its portfolio. Currently, inclisiran is also under review in the United States.FDAReview.

In December 2020, inclisiran was approved by the European Commission (EC) for marketing in Europe under the trade name Leqvio., as an adjunct to diet control, for the treatment of adult primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, specifically: (1) Leqvio in combination with statins or statins and other lipid-lowering therapies, for the treatment of patients who are unable to reach LDL-C treatment goals despite being on the maximum tolerated dose of statins; (2) Leqvio in combination with other lipid-lowering therapies, for the treatment of patients who are statin intolerant or have contraindications to statins.

Leqvio is administered via subcutaneous injection, with one dose given at months 0 and 3,Maintenance phase: Once every 6 months, only 2 injections per year.Compared with cholesterol-lowering therapies available on the market, Leqvio can significantly improve long-term adherence.

It is worth mentioning that,Leqvio is the world's first and only small interfering RNA (siRNA) therapy for lowering cholesterol (LDL-C).. The active ingredient of this drug is inclisran, a first-of-its-kind siRNA with a novel mechanism of action that potently and durably lowers LDL-C levels in patients with atherosclerotic cardiovascular disease (ASCVD), those with ASCVD risk equivalents, and those with heterozygous familial hypercholesterolemia (HeFH) through RNA interference (RNAi). These conditions are risk factors for heart attacks,StrokeThe main driving factors, and may eventually lead to patient death.

Atherosclerosis corresponds to the accumulation of lipids over time, primarily low-density lipoprotein cholesterol (LDL-C), within the arterial walls. The sudden rupture of atherosclerotic plaques can lead to atherosclerotic cardiovascular events, such as heart attacks or strokes. ASCVD accounts for more than 85% of all cardiovascular disease-related deaths10. ASCVD is the leading cause of death in the EU, and the burden of ASCVD in the US is greater than that of any other chronic disease. ASCVD risk equivalents correspond to conditions (such asDiabetes, Heterozygous Familial Hypercholesterolemia).

Despite the widespread use of statins, 80% of high-risk patients do not achieve the guideline-recommended LDL-C target.Clinical data show that in patients receiving the maximum tolerated dose of lipid-lowering therapy but with elevated LDL-C, Leqvio can effectively and continuously reduce LDL-C, with a safety profile similar to placebo. Through its unique twice-yearly dosing regimen, Leqvio can seamlessly integrate into patients' regular medical visits, improving adherence and enhancing patient outcomes.

Inclisiran is the first cholesterol-lowering therapy in the siRNA class, targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), a key mechanism in the body's regulation of LDL-C. The PCSK9 protein reduces the liver's ability to remove low-density lipoprotein cholesterol (LDL-C) from the blood, and LDL-C is widely recognized as a major risk factor for cardiovascular disease (CVD). The PCSK9 target offers a completely new therapeutic approach to combat LDL-C and is considered the most significant advancement in lipid-lowering therapy since statins (such as Lipitor).

As of now, two monoclonal antibody drugs targeting PCSK9 protein have been approved for marketing: Amgen's Repatha and Sanofi/Regeneron's Praluent. Unlike PCSK9 inhibitor monoclonal antibodies, as an RNAi drug, inclisiran works by directly shutting down the production of PCSK9 protein in the liver. (Bioon.com)

Source of the original text:Leqvio®* (inclisiran) reduced LDL-C in people who are overweight or obese