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On August 28, 2024, Novartis announced positive preliminary results from the Phase III V-MONO study with twice-yearly Leqvio (Inclisiran), which met the primary endpoint. Compared with placebo and ezetimibe, Leqvio monotherapy demonstrated clinically and statistically significant reductions in low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD) who were at low to moderate risk and not receiving lipid-lowering therapy.V-MONO isThe First Trial Evaluating Small Interfering RNA (siRNA) Therapy as a Monotherapy to Reduce LDL-C in Patients with Low or Moderate Risk of ASCVD。Novartis plans to present the results of this trial at an upcoming medical conference and share them with regulatory agencies, including the U.S. FDA.
Leqvio was originally co-developed by MDCO and Alnylam. In 2019, Novartis acquired MDCO (licensed by Alnylam) for $9.7 billion.LeqvioIt is a first-in-class siRNA drug targeting PCSK9.Only two subcutaneous administrations per year,The drug isThe world's first and currently only PCSK9 siRNA lipid-lowering drug。Leqvio is priced at $6,500 per year in Europe and the United States, approximately.¥47,000/year; Pricing in China9,988 yuan per injection, approximately 20,000 yuan per year.Leqvio was approved by the FDA for marketing in December 2021 and is indicated for patients with ASCVD and heterozygous familial hypercholesterolemia (HeFH).In July 2023, the indication for Leqvio was expanded to include use in patients with primary hyperlipidemia.Leqvio has been recently100countries have been approved, including the United States, the European Union, Japan, and China."Shreeram Aradhye, MD, Chief Medical Officer and President of Global Drug Development at Novartis, said: 'We are proud to continue advancing the scientific understanding of using siRNA therapies to address one of the world's biggest healthcare challenges, as too many people still struggle to reach their cholesterol goals. This trial adds further evidence for Leqvio in treating various forms of ASCVD, and we will work to help more patients in need.'"Novartis will continue to advance multiple studies evaluating the potential use of Leqvio in primary and secondary prevention.VICTORION-1-PREVENT (V1P) is the only dedicated study of non-statin lipid-lowering therapy in a primary prevention population at high risk as defined by the American College of Cardiology (ACC) and American Heart Association (AHA) guidelines; this outcomes study is expected to complete enrollment later this year. For secondary prevention, the ORION-4 and VICTORION-2-PREVENT (V2P) outcomes studies are proceeding as planned, with data expected to be reported in 2026 and 2027, respectively.
Summary
PCSK9 is the 9th protease K subfamily in the proprotein convertase family, a secreted serine protease mainly synthesized by the liver, which can bind to low-density lipoprotein cholesterol receptors (LDL-R) binds and degrades LDL-R, thereby reducing the clearance of LDL-C in the blood by LDL-R and increasing the level of LDL-C.
The three PCSK9 inhibitors approved for marketing in China include:PCSK9 monoclonal antibody Evolocumab (Repatha, Evolocumab) andAlirocumab (Praluent, Alirocumab) and aPCSK9 siRNA Inclisiran Sodium Injection (Leke Wei, Inclisiran).Currently, multiple companies in China are optimistic about targeting PCSK9. siRNAThe huge market and R&D space for drugs have led to the development of multiple drugs in the pipeline:
Reference: Company Announcement
