The changing landscape of drug clinical trials on cardiometabolic diseases in China, 2009-2021

Abstract

Background: Cardiometabolic disease is a clinical syndrome characterized by multiple metabolic disorders, with atherosclerosis as the core and cardiovascular and cerebrovascular events as the outcome. Drug research and development (R&D) in cardiometabolic diseases has grown rapidly worldwide. However, the development of cardiometabolic drug clinical trials in China remains unclear. This study aims to depict the changing landscape of drug clinical trials for cardiometabolic diseases in China during 2009-2021.

Methods: The detailed information of drug trials on cardiometabolic diseases registered in the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform was collected between January 1, 2009, and July 1, 2021. The landscape of cardiometabolic drug clinical trials was analyzed by the characteristics, time trends, indications, pharmacological mechanisms, and geographical distribution.

Results: A total of 2466 drug clinical trials on cardiometabolic diseases were extracted and analyzed. The annual number of drug trials increased rapidly in the past twelve years. Among all the trials, the bioequivalence trials (1428; 58.3%) accounted for the largest proportion, followed by phase I (555; 22.5%), phase III (278; 11.3%), phase II (169; 6.9%), and phase IV (26; 1.1%). Of 2466 trials, 2133 (86.5%) trials were monomer drugs, only 236 (9.6%) trials were polypills and 97 (3.9%) were traditional Chinese medicine (TCM) compounds. In terms of pharmacological mechanisms, the number of trials in dihydropyridine (DHP) calcium antagonists 321 (11.9%) ranked first, while trials in angiotensin receptor blocker (ARB) 289 (10.7%) and dipeptidyl peptidase-4 (DPP-4) inhibitor 205 (7.6%) ranked second and third place respectively. Of 236 chemical polypills trials, 23 (9.7%) polypills were the combination of DHP calcium antagonists and statins, while others were the combination of two same pharmacological effect agents. As for the geographical distribution of leading units, 36 trials were led by principal investigators (PI) units from Beijing, followed by Jiangsu (n = 29), Shanghai (n = 19), Guangdong (n = 19), and Hunan (n = 19), showing an uneven regional distribution.

Conclusions: Great progress has been made in drug clinical trials on cardiometabolic diseases, especially in antihypertensive agents, hypoglycemic agents, and hypolipidemic agents. However, the insufficient innovation of first-in-class drugs and polypills should be carefully considered by all stakeholders in drug trials.

Keywords: Cardiometabolic disease; Changing landscape; China; Drug clinical trial.

Fig. 1

Flowchart of the selection process Abbreviations: NMPA, National Medical Products Administration

Fig. 2

Annual numbers of initiated cardiometabolic drug clinical trials by major indications in China, 2009–2021 The data ends in July 1st, 2021

Fig. 3

Distribution of clinical trials by drug types and mechanisms The total number of clinical trials would be more than 2466, as a clinical trial could have more than one drug type. Abbreviations: DDP-4, dipeptidyl peptidase-4; GLP-1 RA, glucagon-like peptide-1 receptor agonists; SGLT2, sodium-dependent glucose transporters 2; NPC1L1, Niemann-Pick C1 Like1; PCSK9, Proprotein Convertase Subtilisin/Kexin Type 9

Fig. 4

Distribution of indications in cardiometabolic drug clinical trials (A) Number of clinical trials according to the indication in cardiometabolic diseases. (B) Trials are divided into monomer drug, chemical polypill, and TCM compound. (C) The number of drug trials for different indications. Blue represents one indication. Green represents two indications. Yellow represents three indications, and red represents four indications. (D) In the chemical polypill, the number of drug trials for different indications. The blue represents one indication which suggested that the polypill for one indication. The green represents two indications for polypill. The yellow represents three indications and the red represents four indications. (E) In TCM compounds, the number of drug trials for different indications. The blue represents one indication and the green represents two indications. Numbers above each column of the chart represent the actual number of trials. Abbreviations: TCM, Traditional Chinese Medicine

Fig. 5

Distribution of clinical trials by drug mechanism in chemical polypills Numbers beside each column of the chart represent the actual number of trials. Abbreviations: DHP, dihydropyridine; SGLT2, sodium-dependent glucose transporters 2; NPC1L1, Niemann-Pick C1 Like1; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; DDP-4, dipeptidyl peptidase-4; ARNI, angiotensin receptor-neprilysin inhibitor; GLP-1 RA, glucagon-like peptide-1 receptor agonists

Fig. 6

Geographical distribution of leading units in China