Novo Nordisk's Oral PCSK9 Inhibitor NNC0385-0434 Tablet Receives IND Approval in China for LDL-C Lowering in High-Risk Cardiovascular Patients

By | Pharma Observer

According to the latest announcement from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA), Novo Nordisk’s Class 1 innovative drug, NNC0385-0434 tablets, has received implicit approval for clinical trials. It is being developed to lower low-density lipoprotein cholesterol (LDL-C) in adult patients with heterozygous familial hypercholesterolemia, established cardiovascular disease, or high cardiovascular risk, either as monotherapy or in combination with statins. Publicly available data indicate that this is an oral PCSK9-targeting formulation currently undergoing Phase 2 clinical trials globally.

Screenshot source: CDE official website

High levels of LDL-C in the blood, also known as "bad" cholesterol, increase the risk of patients experiencing serious cardiovascular events. Adults who have previously experienced a heart attack or stroke face up to a one-in-three risk of recurrent serious cardiovascular events. Therefore, elevated LDL-C is one of the key modifiable risk factors for the development of cardiovascular disease.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a hepatic protease. Studies have shown that inhibiting the binding of PCSK9 to the low-density lipoprotein receptor (LDLR) prevents PCSK9-mediated degradation of LDLR, allowing LDLR to be recycled back to the hepatocyte surface. LDLR clears low-density lipoprotein (LDL) from the bloodstream; therefore, an increase in LDLR levels can lower LDL cholesterol (LDL-C) levels and further reduce the risk of myocardial infarction and stroke.

Based on this mechanism, multiple PCSK9 inhibitors have been successfully developed for clinical use, indicated for atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia, as well as for reducing the risk of myocardial infarction, stroke, and angina requiring hospitalization in patients with cardiovascular disease.

It is worth noting that most currently marketed PCSK9 inhibitors are injectable monoclonal antibodies. In contrast, NNC0385-0434, currently under development by Novo Nordisk, is an oral PCSK9 inhibitor. Compared with injectable formulations, oral formulations offer potential advantages in terms of administration convenience and patient adherence.

According to publicly available information, Novo Nordisk is currently conducting a Phase II clinical trial to investigate how NNC0385-0434 tablets lower cholesterol in patients with heart disease or those at high risk for the condition.

References:

[1] Center for Drug Evaluation, National Medical Products Administration, China. Retrieved Sep 13, 2021, from https://www.cde.org.cn/main/xxgk/listpage/369ac7cfeb67c6000c33f85e6f374044

[2].A Research Study Looking at How NNC0385-0434 Tablets Work to Lower Blood Cholesterol in People With Heart Disease or a High Risk of Heart Disease. From https://www.clinicaltrials.gov/ct2/show/NCT04992065?term=NNC0385-0434&draw=2&rank=3

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