Sanofi's PCSK9 Monoclonal Antibody Alirocumab Nears Approval in China

Recently, the marketing application for Sanofi’s PCSK9 monoclonal antibody alirocumab (brand name: Praluent; acceptance numbers: JXSS1800032, 33, 34, and 35) has been updated to “under review,” with approval expected in the near future. Currently, only two PCSK9 monoclonal antibodies are marketed globally: alirocumab, jointly developed by Sanofi and Regeneron, and evolocumab from Amgen. In China, only evolocumab is currently available; alirocumab will become the second PCSK9 monoclonal antibody approved for marketing in the country.

(Source: NMPA)

The Next Generation of Lipid-Lowering Drugs After Statins

PCSK9 (proprotein convertase subtilisin/kexin type 9) binds to low-density lipoprotein (LDL) receptors (LDLR), thereby reducing the liver’s ability to clear LDL cholesterol (LDL-C) from the bloodstream. PCSK9 monoclonal antibodies inhibit the binding of PCSK9 to LDLR, increasing the number of LDLRs available to clear LDL from the blood, thus lowering LDL-C levels.

PCSK9 monoclonal antibodies are the most promising class of lipid-lowering drugs since statins, used to reduce the risk of cardiovascular events and to treat primary hyperlipidemia (including heterozygous familial hypercholesterolemia) and homozygous familial hypercholesterolemia.

The prevalence of dyslipidemia among Chinese adults has risen significantly. According to the Report on Cardiovascular Diseases in China 2018, the prevalence of dyslipidemia among Chinese adults reached 40.4% in 2012. There remains substantial room for improvement in the awareness, treatment, and control rates of dyslipidemia among Chinese adults. PCSK9 inhibitors can address the unmet clinical needs of patients with poorly controlled dyslipidemia.

Two PCSK9 Inhibitors Launched Globally

Currently, only two PCSK9 inhibitors have been approved for marketing worldwide: Evolocumab (Repatha) from Amgen and Alirocumab (brand name: Praluent), jointly developed by Sanofi and Regeneron. Both products are monoclonal antibodies targeting PCSK9, and no small-molecule drug-based PCSK9 inhibitors have yet been launched on the market.

Both alirocumab and evolocumab are injectable agents administered every two weeks, with the option of extended dosing intervals of every four weeks at higher doses. Compared with once-daily oral lipid-lowering medications, they do not present adherence barriers. They were approved by the FDA in July and August 2015, respectively. Evolocumab was approved by the National Medical Products Administration (NMPA) on July 31, 2018, becoming the first PCSK9 inhibitor marketed in China, and has since been approved for three indications. The domestic price of evolocumab is RMB 1,298 per prefilled syringe, approximately 80% of its current U.S. price.

Overview of Globally Marketed PCSK9 Inhibitors

(Source: FDA, NMPA)

In 2018, the sales of alirocumab and evolocumab were $310 million and $550 million, respectively, representing a significant gap compared to the multi-billion-dollar sales scale previously achieved by statins. The primary reason for this disparity was the high annual list price of approximately $14,000 for both drugs, which resulted in substantial out-of-pocket costs for patients not covered by insurance, thereby hindering market adoption. In March and October 2018, alirocumab and evolocumab underwent price reductions of 60%, bringing their annual costs down to approximately $6,000.

Global Sales of Marketed PCSK9 Inhibitors (in USD 100 million)

(Source: Fierce Pharma)

Among domestic players, Junshi and Innovent are progressing faster

Among domestically produced products, the PCSK9 monoclonal antibodies from Junshi Biosciences and Innovent Biologics successively initiated Phase II clinical trials in early 2019 and are currently progressing at a relatively fast pace. Notably, Junshi’s product covers the three indications for evolocumab already approved overseas. Hengrui Medicine and Akeso Biopharma are also advancing rapidly, closely following behind.

(Source: CDE, Product Labeling)

"Detailed Information: 'Domestic Biotech R&D Pipeline Series - Junshi Biosciences – Actively Expanding PD-1 Indications While Covering Multiple Targets Including BTLA, PCSK9, and BLyS'."

Original Title: Market Launch | Breaking! The Second PCSK9 Monoclonal Antibody Is Set to Launch in China