PCSK9  (Proprotein Convertase Subtilisin/kexin type 9) Inhibitors Market: Competitive Landscape, Pipeline, and Market Analysis 2022

Proprotein Convertase Subtilisin/kexin type 9 (PCSK9) is a serine protease (protein) targeting LDL receptors for degradation, thereby reducing the liver’s ability to eliminate LDL-cholesterol (LDL-C), the so-called bad cholesterol, from the blood. PCSK9 inhibitors exert their action by binding to PCSK9 and preventing it from binding to LDL receptors on the surface of the liver, facilitating the presence of more LDL receptors on the surface of the liver to clear LDL-C from the blood. Some of the primary indications of PCSK9 inhibitors are reducing the risk of myocardial infarction, stroke, unstable angina, and coronary revascularization in patients with cardiovascular diseases.

Additionally, it can also be used as an adjunct in patients with primary hyperlipidemia, heterozygous familial hypercholesterolemia (HeFH), and homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C levels in the body. As per the Global Burden of Disease Study, approximately 4.4 million deaths were attributed due to elevated LDL cholesterol in 2019. Moreover, according to the World Heart Federation report on cholesterol roadmap update 2022, familial hypercholesterolemia (FH) a genetic disorder found in people of all races and ethnicities, affects approximately 28 million people worldwide as FH remains mostly underdiagnosed and undertreated due to low awareness about the condition. Amgen, Sanofi, Alnylam, and Novartis are the few numbers of key players with approved PCSK9 inhibitors in the market. Other than these, Pfizer, LIB Therapeutics, and Shanghai Junshi Bioscience are currently conducting phase III of clinical trials.

Key Developments

• In May 2023, LIB Therapeutics’ PCSK9 inhibitor, Lerodalcibep has shown some variable responses in patients with homozygous familial hypercholesterolemia (HoFH).
• In June 2023, Novartis AG identified diamino cyclopentyl pyridine derivatives acting as PCSK9 inhibitors and thus reported to be useful for the treatment of hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, sitosterolemia, vascular inflammation, atherosclerosis, peripheral vascular and coronary heart disease, among others.

Approved PCSK9 Inhibitors

• REPATHA (Evolocumab)
• PRALUENT (Alirocumab)
• LEQVIO (Inclisiran)

Pipeline Molecules - PCSK9 Inhibitors

• LGT209 - Phase-II
• RG7652 - Phase-II
• Ongericimab (JS002) - Phase-III
• Tafolecimab (IBI306) - Phase-III
• Ebronucimab (AK102) - Phase-III
• Lerodalcibep (LIB003) - Phase-III
• NNC0385-0434 - Phase-I
• VXX-401 - Phase-I
• MK-0616 - Phase-I
• AZD0780 - Phase-I
• VERVE-101 - Phase-I

Clinical Activity and Development of PCSK9 Inhibitors

Currently, PCSK9 inhibitors are being developed by 27 companies, with 30 products in the pipeline and most of them are in phase III of the clinical trial.

• In Dec 2021, Akeso, Inc. announced that Ebronucimab (PCSK9 monoclonal antibody - AK102), jointly developed by the Akeso and Dawnrays Biotechnology Capital Ltd., completed patient enrollment early in a pivotal registrational phase III clinical trial in the People's Republic of China for the treatment of primary hypercholesterolemia and mixed hyperlipidemia.
• In Nov 2022, Innovent Biologics, a biopharmaceutical company announced the results of a phase 3 clinical study (CREDIT-1) of tafolecimab (IBI306), a recombinant fully human anti-PCSK-9 monoclonal antibody, in Chinese patients with non-familial hypercholesterolemia (non-FH). Tafolecimab was found safe and well tolerated and its safety profile was like those of other PCSK9 monoclonal antibodies.