Novartis Announces NMPA Approval of Leqvio (Inclisiran), a First-in-Class siRNA Therapy for Hypercholesterolemia in China

On August 22, Novartis announced that its small interfering RNA (siRNA) therapy, Inclisiran Sodium Injection (trade name: Leqvio, Inclisiran), was approved for marketing by the National Medical Products Administration, as an adjunct to diet for the treatment of adult patients with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia. This includes: combination therapy with statins or with statins and other lipid-lowering therapies in patients who are unable to reach LDL-C (low-density lipoprotein cholesterol) goals despite being on the maximum tolerated dose of statin therapy, and monotherapy or combination therapy with other lipid-lowering therapies in patients who are intolerant or contraindicated to statins.

Inclisiran is a first-in-class siRNA drug targeting PCSK9, which requires only two subcutaneous injections per year. It was approved by the FDA in December 2021 (brand name: Leqvio) for patients with atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH). In July 2023, its use was expanded to include patients with primary hyperlipidemia. Inclisiran is the first and only siRNA therapy to lower LDL-C.

Results from the pivotal Phase III, placebo-controlled, double-blind ORION (ORION-9, -10, and -11) clinical trials showed that Inclisiran can continuously reduce LDL-C levels by up to 52% in patients who are unable to reach their LDL-C goals despite being on the maximum tolerated dose of statins. Additionally, Inclisiran’s dosing regimen, which requires only two injections per year after the initial doses at month 1 and month 3, has the potential to address long-term patient compliance challenges.

In November 2022, Novartis announced the results of the open-label extension study (ORION-3) of the Phase II ORION-1 trial. The results showed that the LDL-C levels of participants continued to decrease during the four-year study period. In patients receiving Leqvio treatment, LDL-C decreased by an average of 47.5% (95% CI: -50.69, -44.27) from baseline (Day 1 of ORION-1) to Day 210. Additionally, approximately 80% of patients had LDL-C levels below 70 mg/dL.

In the series of clinical trials conducted by Novartis on Leqvio, the ORION-3 study has the longest safety follow-up period. Overall, Leqvio was well-tolerated, with a safety profile consistent with data from previous Phase III studies lasting 18 months. The most common drug-related treatment-emergent adverse events were mostly mild to moderate, consistent with prior studies.

According to the PharmaCube database, Novartis is conducting five Phase III clinical trials in China, including a Phase III study of Inclisiran monotherapy in Chinese adult patients with low or moderate risk ASCVD and elevated LDL-C (CTR20231739), a multicenter study evaluating the preventive effect on major adverse cardiovascular events in high-risk primary prevention patients after use (CTR20231501), a Phase IIIb study assessing atherosclerotic plaque progression in patients with non-obstructive coronary artery disease and no prior cardiovascular events (CTR20221867), a Phase III study evaluating the reduction of the risk of major adverse cardiovascular events in patients with established cardiovascular disease (CTR20213277), and a Phase III study for ASCVD or high-risk ASCVD Asian patients with elevated LDL-C despite being on dietary control and maximum tolerated statin therapy (with or without other lipid-lowering therapies) (CTR20202214).

Copyright © 2023 PHARMCUBE. All Rights Reserved.

Welcome to forward, share, and reasonably cite. When citing, please clearly indicate the source of the article; if you need to reproduce it, please leave a message on the WeChat Official Account or send a message, and include the name and ID of the official account.

Disclaimer: The information in this WeChat article is for general reference only and should not be directly used as decision-making content. PharmaCube assumes no responsibility for any loss incurred by any party due to the use of the content herein.

Exciting Preview

Online Live Streaming & Offline Salon

↑ Click to scan the QR code and register for the conference ↑