Novo Nordisk's Oral Semaglutide Approved in China for Type 2 Diabetes

Jan 26, 2024 15:54 CST Updated 15:54

Novo Nordisk

Insulin Developer and Manufacturer

▎WuXi AppTec Content Team Report

Today(On January 26), the official website of China's National Medical Products Administration (NMPA) announced that Novo NordiskSemaglutide TabletsThe new drug marketing application has been approved.. Public information shows,Semaglutide tablets are an oral GLP-1 receptor agonist (GLP-1RA) medication., Its emergence has broken the pattern where patients with type 2 diabetes need to receive GLP-1RA injections daily or weekly, offering them a less invasive and convenient treatment option for blood sugar control.

Screenshot source:NMPA Official Website

Semaglutide is a glucagon-like peptide-1 (GLP-1) analog.GLP-1 is a peptide hormone secreted by intestinal cells. It stimulates insulin secretion and inhibits glucagon secretion by binding to the GLP-1 receptor, thereby promoting glucose metabolism. At the same time, it can also slow gastric emptying and suppress appetite. Natural GLP-1 is secreted after meals when stimulated by glucose. In patients with type 2 diabetes, the secretion level of GLP-1 is significantly reduced, which is one of the important reasons for poor blood glucose control.

According to the earlier public information from Novo Nordisk, semaglutide introduced some innovative optimizations to the human GLP-1 polypeptide chain during its development. These mainly include enhancing its binding to albumin, which reduces renal clearance and protects it from metabolic degradation—this is also the primary mechanism behind semaglutide’s extended half-life. Additionally, through peptide chain optimization, semaglutide can resist degradation by the DPP-4 enzyme, maintaining its stability.These breakthrough peptide structure optimizations have extended the half-life of semaglutide to 7 days, enabling once-weekly dosing with very stable blood drug concentrations.。Previously,SemaglutideInjectable FormulationsAlready in ChinaApprovedFor the treatment of type 2 diabetes.

Semaglutide tablets are a compound preparation of semaglutide and the absorption enhancer (SNAC).The uniqueness of this oral formulation lies in the fact that the combination of SNAC and semaglutide enables the latter to be absorbed in the stomach.. At the same time, the dissolution of SNAC in the stomach can locally increase the pH of the environment, which not onlyImprove the solubility of semaglutide and prevent its degradation by peptidases in the stomach.. Because the peptidase in the stomach requires an acidic environment to function and has almost no activity in a neutral pH environment. In September 2019, oral semaglutide (brand name Rybelsus) was launched in the United States.ApprovedIndicated, in combination with diet and exercise, to improve glycemic control in adults with type 2 diabetes.

According to the press release issued by Novo Nordisk in February 2022, the results of the Phase 3 clinical PIONEER 1/2/3/4/5/7/8 series studies for patients with type 2 diabetes showed that the semaglutide tablet can:1）Significantly reduce HbA1c levels by up to 1.5%; 2) Significantly increase HbA1c target achievement rate by up to 80%; 3) Significantly reduce body weight by up to 5.0kg; 4) Significantly decrease systolic blood pressure by up to 7mmHg while regulating lipid profile.The pharmacodynamic curve of semaglutide tablets is consistent with that of the subcutaneous injection formulation.

Screenshot source: Reference [4]

Notably, the PIONEER 11 study and the PIONEER 12 study areMainly in the Chinese populationThe international multicenter clinical trials include 520 patients with type 2 diabetes who had poor blood glucose control through diet and exercise in the former, and 1,444 patients with type 2 diabetes who had inadequate blood glucose control with metformin in the latter. These two studies will further validate the efficacy and safety of semaglutide tablets in the Chinese population.Currently, both studies have been completed.。

According to the China Drug Clinical Trial Registration and Information Disclosure Platform,In addition to the PIONEER 11 study and the PIONEER 12 study,DepartmentThe tablet form of semaglutide is also currently undergoing a trial in China.Early Alzheimer's DiseaseA randomized, double-blind, placebo-controlled, Phase 3 international multicenter (including China) clinical trial (EVOKE plus) on the efficacy and safety in subjects, as well as aType 2 DiabetesThe Phase 3 international multicenter (including China) cardiovascular outcomes trial (SOUL) conducted among patients. This meansDepartmentMeglutideIt is expected to benefit more patients in the future.

References:

[1] Drug Approval Certificate Delivery Information Released on January 26, 2024. Retrieved Jan 26 2024, from https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20240126151815151.html

[2] [Semaglutide Vision New Horizon] Semaglutide Weekly Formulation — Molecular Structure and Mechanism of Action. Retrieved Nov 28, 2020, from https://mp.weixin.qq.com/s/40XmluRhRyrMvXAd-Zc8Jw

[3] Knudsen and Lau. (2019). The Discovery and Development of Liraglutide and Semaglutide. Front. Endocrinol., https://doi.org/10.3389/fendo.2019.00155.

[4] [2022 NNDU] Breaking Report of the 21st Novo Nordisk Diabetes Forum. Retrieved Feb 26, 2022, from https://mp.weixin.qq.com/s/bYXjBfGr7pz-luUIExyN0g

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