FDA Approves Novartis’ Leqvio (inclisiran), First-in-Class siRNA Therapy for LDL-C Reduction with Just Two Annual Injections

Novartis(Novartis) recently announced that the U.S. Food and Drug Administration (FDA) has been approvedLeqvio (inclisiran), the first and only small interfering RNA (siRNA) drug to lower LDL-C ("bad cholesterol").siRNA`) Therapy`In the United States, Leqvio is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of: adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. The impact of Leqvio on cardiovascular morbidity and mortality is currently under investigation.Clinical TrialExplore in China.

In December 2020, inclisiran received approval from the European Commission (EC) for marketing in Europe under the brand name Leqvio as an adjunct to dietary control for the treatment of adult patients with 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 patients who are unable to reach LDL-C treatment goals on the maximum tolerated dose of statins; (2) Leqvio in combination with other lipid-lowering therapies for 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: Administered once every 6 months, only 2 injections needed per year.Compared with cholesterol-lowering therapies available on the market, Leqvio can significantly improve long-term compliance.

Notably, 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 inclisiran, a first-of-its-kind siRNA with a novel mechanism of action that potently and durably reduces 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.

FDAApproval of Leqvio Based on Comprehensive Phase 3 ORION-9, -10, -11 TrialsClinical TrialThe results. In these trials, a total of 3,457 patients with ASCVD or HeFH were enrolled who had elevated LDL-C levels despite receiving the maximum tolerated dose of statin therapy. The data showed that at the 17th month of treatment,Compared with placebo, Leqvio effectively and continuously reduced LDL-C levels by 52%., well-tolerated, with safety comparable to placebo. The most common side effects are mild to moderate injection site reactions (including pain, redness, rash), arthralgia, urinary tract infection, diarrhea, chest tightness, leg or arm pain, and shortness of breath.

According to the license and cooperation agreement signed with Alnylam Pharmaceuticals, the leader in RNAi therapy,NovartisHas obtained the global rights for the development, manufacturing, and commercialization of Leqvio.

NovartisCEO Vas Narasimhan stated, "Leqvio is a revolutionary approach to lowering LDL-C and creates new possibilities for how the healthcare system can impact cardiovascular disease, which is one of the most significant public health challenges of our time. We now have the opportunity to collaborate with partners to deliver the first approved siRNA therapy for lowering LDL-C across the United States to treat ASCVD."

Atherosclerosis corresponds to the accumulation of lipids over time, primarily low-density lipoprotein cholesterol (LDL-C), within the arterial walls. The unexpected 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 U.S. 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 fail to achieve the LDL-C goals recommended by guidelines. Clinical data shows that in patients receiving the maximum tolerated dose of statins but still experiencing elevated LDL-C, Leqvio can effectively and sustainably reduce LDL-C levels by 52% compared to placebo, 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.PCSK9 Protein Reduces the Liver's Ability to Clear 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 Advance in Lipid-Lowering Therapy Since Statins (e.g., Lipitor).

Inclisiran is an siRNA that utilizes the natural process of RNA interference in the human body, binding to the mRNA encoding PCSK9 protein, reducing mRNA levels through RNA interference, and preventing the liver from producing PCSK9 protein, thereby enhancing the liver's ability to remove LDL-C from the blood and achieving a reduction in LDL-C levels.

As of now, two monoclonal antibody drugs targeting PCSK9 protein have been approved for marketing: Repatha from Amgen and Praluent from Sanofi/Regeneron. 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:FDA approves Novartis Leqvio® (inclisiran), first-in-class siRNA to lower cholesterol and keep it low with two doses a year