Remimazolam Tosylate

In recent years, among the new anesthetic sedation drugs launched on the market, Remazolam has undoubtedly aroused widespread concern in the industry. The drug was designed and synthesized by GlaxoSmithKline (GSK) in 1999, and after several corporate transfers, it was approved for market in China, the United States, Europe and other countries and regions around 2020. However, there are significant differences in the market performance of remazolam across countries. According to 2023 data, the drug's sales in China are about $40 million, while in the United States it is only $800,000, accounting for only 2% of the Chinese market. The reasons for this difference are worth exploring in depth. Remazolam is an ultra-short-acting GABAA receptor agonist whose design is inspired by midazolam and remifentanil, combining the properties of both. It is rapidly metabolized by carboxylesterases in the liver to produce inactive metabolites, resulting in rapid sedation resolution and short sedation recovery time. Remazolam's development history dates back to 1999, when GSK designed and synthesized the drug based on remifentanil's properties and filed a patent application. The patent was then transferred to TheraSci in the United Kingdom. Paion began developing the drug in 2008. Due to the instability of remazolam's free base, Paion developed remazolam benzenesulfonate, while Hengrui Pharmaceuticals adopted remazolam in the form of (toluene sulfonate) salt. At present, these two salt types of remazolam have been listed, of which Remazolam toluene sulfonate is only listed in China, while Remazolam benzenesulfonate is listed in China, Japan, the United States, Europe and other countries, but there are differences in indications. In the Chinese market, RenFCM obtained the Chinese market rights of Remazolam besylate in 2012, and was approved by the State Food and Drug Administration for sedation in colonoscopy in 2020, followed by the induction and maintenance of general anesthesia and the indication of bronchoscopic sedation. In the United States, Remazolam besylate was approved in July 2020 under the trade name Byfavo for a 30-minute sedation procedure marketed by Eagle. Remazolam besylate is approved for induction and maintenance of general anesthesia in Japan and South Korea. It is worth noting that in the first quarter of 2024, Paion was acquired by China's Renfu Pharmaceutical, which means that the global interests of Remazolam besylate have been vested in Renfu Pharmaceutical. Remazolam toluene sulfonate was first approved for sale in China in 2019 for indications including induction and maintenance of general anesthesia and sedation during colonoscopy. The difference in sales in the U.S. and China markets may be related to the different range of indications approved for remazolam in different countries. In the United States, Remazolam is only approved for procedural sedation, while in China, its approved indications include general anesthesia and sedation, and sales are significantly higher than in the United States. In addition, the difference in sales performance between China and the United States may also be related to concerns about remazolam metabolites. Remazolam is metabolized in the body to produce methanol, which may be further oxidized to formaldehyde and formic acid, and formaldehyde is potentially cytotoxic. As a result, the FDA requires remazolam to be administered only within 0.5 hours to avoid the buildup of methanol and its metabolites to dangerous levels. At present, other anesthetic sedatives commonly used in clinical practice, such as propofol, benzodiazepines (represented by midazolam), and α-receptor agonists (represented by dexmetropil), all have their own shortcomings. Although Remazolam still has room for improvement in some aspects, its unique advantages, such as rapid onset, rapid metabolism, rapid sedation recovery, etc., make it a potential application value in the field of anesthesia sedation. With the advancement of medical technology and the in-depth exploration of clinical applications, there may be an improved version of remazolam in the future, bringing new options to the field of anesthesia sedation.