Jiangsu Vcare's Class 1 Novel Antiplatelet Drug Vicagrel Capsule Approved for Phase II Clinical Study in Ischemic Stroke

　　Recently, Vicagrel capsules, a Class 1 novel antiplatelet agent developed by Jiangsu Vcare PharmaTech Co., Ltd. (Jiangsu Vcare), received Clinical Trial Approval from the NMPA for the target indication of minor ischemic stroke (MIS) or transient ischemic attack (TIA). The related Phase II clinical trial is set to begin shortly.

　　This approval for an expanded indication marks another significant milestone for Vicagrel capsules, following its first clinical indication being investigated, which is ACS(Coronary Heart Disease). Currently, a Phase III bridging study for Vicagrel is underway in China, while US-based clinical trials are also progressing rapidly, aiming for concurrent submissions in the future to both Chinese and US regulatory authorities.

　　About Vicagrel

　　Vicagrel is an industry-academia-research collaboration project between Jiangsu Vcare Pharmaceutical Technology Co., Ltd. and China Pharmaceutical University. The company holds full rights to the project. Early-stage research findings were fully published in the JMC, a publication of the ACS, and the project was highlighted by SciBX (published by Nature).

　　As a novel antiplatelet agent, Vicagrel, based on its ingenious structural design, offers four core advantages over existing clinical drugs:

　　1. Metabolic Pathway Advantage: Vicagrel undergoes its key activation step via intestinal esterases, breakthrough bypassing clopidogrel's strong dependence on hepatic CYP2C19 metabolism. This holds clinically promise for overcoming "clopidogrel resistance" caused by different CYP2C19 genotypes (*1, *2, *3 locus mutations). Furthermore, Phase III bridging data in rapid metabolizers (*17 locus mutation) suggesting it effectively avoids the high bleeding risk associated with excessive platelet inhibition due to clopidogrel's over-metabolism.

　　2. Safety Profile: Vicagrel's active metabolite is identical to clopidogrel's, potentially retaining clopidogrel's favorable safety profile. This avoids the high bleeding risks associated with ticagrelor and prasugrel, and may also alleviate bleeding concerns common among elderly patients.

　　3. Reduced Drug-Drug Interactions (DDIs): Vicagrel's unique metabolic pathway effectively avoids common DDIs seen with clopidogrel and drugs like repaglinide or proton pump inhibitors (PPIs), offering a solution for polypharmacy in elderly patients.

　　4. Improved Efficiency & Reduced Side Effects: Vicagrel avoids clopidogrel's inefficient initial metabolic step, resulting in a significantly lower effective dose (only one-fifteenth that of clopidogrel). This implies a further reduction in dose-related side effects, positioning Vicagrel as a novel antiplatelet drug with potentially superior efficacy and more manageable safety profile.

　　About CYP2C19 Genetic Diversity

　　CYP2C19 is a crucial member of the CYP450 enzyme subfamily 2, expressed in the liver, and is a vital drug-metabolizing enzyme in humans. However, studies show that 55% of the Asian population carries loss-of-function mutations in the CYP2C19 allele (CYP2C19*2, CYP2C19*3), while 5% carry a gain-of-function mutation (CYP2C19*17). Clinically, individuals are categorized into five metabolic phenotypes based on capacity: Ultra-rapid Metabolizer (UM), Rapid Metabolizer (RM), Normal Metabolizer (NM), Intermediate Metabolizer (IM), and Poor Metabolizer (PM).

　　The metabolism of the established antiplate drug clopidogrel relies heavily on CYP2C19. During treatment, IM/PM patients experience varying degrees of clopidogrel resistance due to insufficient metabolic enzyme activity, leading to reduced efficacy or treatment failure, thereby increasing the risk of stroke and cardiovascular events. Conversely, UM/RM patients face an increased risk of bleeding events due to heightened responsiveness to clopidogrel. Overcoming clopidogrel resistance and potential hyper-rresponsiveness and bleeding are thus critical unmet clinical needs. Vicagrel, leverags its advantageous metabolic pathway, effectively circumvents this issue, holding promise to improve patient clinical outcomes.

　　About Ischemic Stroke

　　Ischemic stroke, also known as cerebral infarction, accounts for 80% of all strokes. It is characterized by localized ischemic necrosis or cerebral softening caused by ischemia and hypoxia, with sudden onset and rapid progression. Failure to receive timely treatment significantly increases the risks of disability and death, imposing a substantial burden on patients and families.

　　Large-scale epidemiological studies in China reveal that from 1990 to 2017, stroke consistently ranked as the leading cause of death, with a mortality rate as high as 149 per 100,000 population and an average age at death of 58 years. Not only are middle-aged and elderly individuals high-risk groups, but the age of onset is also trending downward. The indication approved for Vicagrel pertains to the minor form of ischemic stroke, which is also the most common type of stroke occurrence.

　　Minor ischemic stroke (MIS) or transient ischemic attack (TIA), due to relatively mild clinical symptoms, are often overlooked, leading to a higher recurrence rate compared to other stroke types. As an antiplatelet agent within antithrombotic therapy, Vicagrel effectively inhibits platelet activation, aggregation, and release, with the potential to reduce the recurrence risk and the incidence of disabling recurrent events in MIS/TIA patients.