Novartis' Twice-Yearly siRNA Lipid-Lowering Drug Inclisiran Launched Across China at ¥9,988 per Dose

Nov 02, 2023 17:23 CST Updated 17:23

Novartis

Drug Development and Manufacturing

Recently, Novartis has developedInclisran Sodium Injection (Inclisran), a semi-annual ultra-long-acting lipid-lowering drugAdministered in multiple locations across China, with the first prescriptions already issued in Beijing, Shanghai, Jiangsu, and Wuhan., with each dose priced at 9,988 yuan!

Inclisran is the world's first siRNA PCSK9 inhibitor, its ultra-long duration gives it an advantage over PCSK9 monoclonal antibodies. This drug was approved in China this August, and also approved for marketing in the same month is Innovent Biologics' PCSK9 monoclonal antibody, Torlipasir. Now that Novartis has set a higher-than-expected price, a price war for the PCSK9 target may be triggered.

New Star in Lipid-Lowering —— PCSK9 Inhibitors

Cardiovascular disease (CVD) is the leading cause of death globally, accounting for approximately 30% of total deaths worldwide. Atherosclerotic cardiovascular disease (ASCVD) is the primary contributor to mortality. The occurrence of ASCVD involves multiple risk factors, with dyslipidemia characterized by elevated low-density lipoprotein cholesterol (LDL-c) or cholesterol being a significant risk factor. Reducing LDL-c levels can significantly decrease the incidence and mortality risk of ASCVD.

Currently, statins are the first-line clinical drugs for lipid control. This class of drugs effectively reduces total cholesterol (TC) and low-density lipoprotein (LDL) by blocking cholesterol synthesis. Atorvastatin (Lipitor), as the BIC of this class of drugs, has occupied the top sales position for many years, with global cumulative sales reaching approximately 200 billion US dollars to date.

However, statin therapy is associated with adverse side effects, including statin-associated muscle symptoms, hepatotoxicity, the possibility of developing type 2 diabetes, and an increased risk of hemorrhagic stroke. Moreover, approximately 50% of individuals using statins are unable to lower their LDL-C levels to the expected level.

Unlike statins that block cholesterol synthesis, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors regulate blood lipids by degrading LDL-C. PCSK9 inhibitors provide a novel therapeutic approach for lowering LDL-C, offering new hope for the treatment of patients with refractory hypercholesterolemia and lipid management in extremely high-risk ASCVD patients.

Novartis and Innovent PCSK9 New Drugs Approved at the Same Time,

Price War Ready to Break Out

In 2015, Evolocumab, developed by Amgen/Astellas, and Alirocumab, developed by Regeneron/Sanofi, were successively approved for the treatment of patients with hereditary hypercholesterolemia or high-risk ASCVD. Both of these monoclonal antibodies are administered via subcutaneous injection once every two weeks, which poses a challenge to the convenience of drug administration for chronic patients requiring long-term medication.

In 2020, Inclisiran (Leqvio), developed by Novartis/Alnylam, was the first to be approved for marketing in the European Union. Inclisiran is an siRNA gene therapy targeting PCSK9 designed and developed by Alnylam based on its GalNAc delivery system. It enables long-acting dosing (after two injections within the first three months, one injection every six months), reduces the frequency of medication for patients, and greatly improves the convenience of patient medication.

With its excellent clinical advantages, Inclisiran achieved sales of $112 million in 2022. Novartis believes that the growth rate of Inclisiran is basically consistent with that of Sacubitril/Valsartan (Entresto), which reached $4.644 billion in sales for the whole year of 2022 and is expected to become Novartis' next core growth point.

In China, evolocumab and alirocumab were successively approved for marketing in 2018 and 2019. This August, the National Medical Products Administration (NMPA) further approved the market launch of Inclisiran Sodium Injection (inclisiran, brand name Leqovi) by Novartis and Torliprocept Injection by Innovent Biologics.

Innovent Biologics' Toripalimab was priced first: 1,388 yuan per injection, with an annual treatment cost of approximately 44,000 yuan. However, Novartis then priced Inclisiran Sodium at 9,988 yuan per injection, with an annual treatment cost of less than 20,000 yuan, putting pressure on other PCSK9 inhibitors to lower their prices!

In addition, Junshi Biosciences' Anggrekizumab, Akeso Biopharma's Inucizumab, and Hengrui Medicine's Recarcilizumab have also submitted marketing applications.

Multiple oral PCSK9 inhibitors have entered clinical stages globally, including Merck's MK-0616, Novo Nordisk's NN-6435, AstraZeneca's AZD-8233, and Civi Pharmaceuticals' CVI-LM001, among others. It is foreseeable that the competition for PCSK9 lipid-lowering drugs will become increasingly intense.

Summary

Currently marketed PCSK9 inhibitors have demonstrated the advantages of this target in lipid-lowering, bringing therapeutic hope to refractory hyperlipidemia and familial hypercholesterolemia.

But there are many affordable options for lipid-lowering drugs, and it is not easy for new mechanism lipid-lowering drugs to gain a foothold in the Chinese market. Recently, Novartis offered an unexpectedly low price for its siRNA PCSK9 inhibitor, indicating that the price competition for novel lipid-lowering drugs has already begun ahead of schedule. On the other hand, this competition also brings more cost-effective treatment options to patients.

Source: Yaoke News, Official Account "Cell and Gene Therapy Field",Publicly Available Online Informationetc.

E.N.D