Hengrui Change of Rimazolam Salt Type to Obtain Class I New Drug

The structure of the compound is finally listed in the salt form, which can often improve some physical and chemical property data in the free state of the drug, which is also part of the research and development of most innovative drugs. However, on the basis of published compounds, a Class I new drug can be obtained only by changing the salt form, and has developed to the NDA stage in China. Such examples are really rare, after all, it is unlikely that the original research company will miss a better salt type. However, it is such a very small probability event that Hengrui has caught. This product is currently in the NDA stage and has obtained the domestic priority review qualification.

Introduction of remazolam tosylate

Rimazolam is a short-acting GABAA receptor agonist developed by Paion, Germany. It is a benzodiazepine central nervous system drug. Rumazolam tosylate is a salt compound of Rumazolam developed by Jiangsu Hengrui, which has higher stability than Rumazolam, and has been submitted for listing in China for intravenous anesthesia, analgesia during microscopic examination, preoperative anesthesia and ICU sedation.

Current status of drugs with the same target

The number of resmazolam tosylate drugs listed with the same target has reached 74, 3 NDA application status, 11 clinical phase III varieties, 15 clinical phase II varieties, 27 clinical phase I varieties, and 4 withdrawn drugs (compound amitriptyline hydrochloride/chlorazone, bubarbital, apypitan and methaqualone respectively). In terms of clinical status, 24 were in progress, 10 were not progressing, and 28 were terminated.

In terms of Class I new drugs in China, the most advanced in research and development is resazolam tosylate from Jiangsu Hengrui. The following phase III clinical products are Paion Pharma/Remazolam besylate of Yichang Renfu Pharmaceutical and HSK-3486 of Haisco respectively. Phase II clinical products are D-Pharm/Jiangsu Enhua Pharmaceutical DP-VPA. Phase I clinical products are SPT-07A of Suzhou Huyun, Suzhou Wangshan Wangshui Biomedicine/Shanghai Institute of Materia Medica, Chinese Academy of Sciences/Shanghai Special Pharmaceutical Technology.

Progress of Remazolam Tosylate in China

In June 2012, the General Administration of Food and Drug Administration undertook the Class 1 New Drug Clinical Application (IND) submitted by Hengrui.

In April 2013, remazolam tosylate obtained clinical approval for 1.1 Chinese drugs.

In October 2013, a phase I clinical study of resmazolam tosylate was initiated.

In May 2017, remazolam tosylate was approved by CFDA and entered phase III clinical practice.

In March 2018, remazolam tosylate was declared for production in China.

In April 2018, according to the Opinions of the General Administration on Encouraging Drug Innovation to Implement Priority Review and Approval (Food and Drug Administration [2017] No. 126),CDE organized experts to review and demonstrate the drug registration application for priority review. Jiangsu Hengrui's resazolam tosylate was selected for "obvious therapeutic advantages compared with existing treatment methods".

Pharmacological and clinical information

Jiangsu Hengrui does not disclose much information about the product resazolam tosylate, and its clinical indications are mainly for sedation and anesthesia of gastroscopy and colonoscopy. From the relevant reports of the original resazolam, it can be seen that resazolam combines the safety of midazolam with the effectiveness of propofol (propofol), but the stability of free base is poor and the druggability is not high, on the other hand, Jiangsu Hengrui uses toluene sulfonate instead of benzene sulfonate of the original research company on the basis of remazolam, which is relatively less toxic, so relatively speaking, the clinical safety is higher..

Summary

From a long-term perspective, the listing of Remazolam tosylate will become a new performance growth engine for Hengrui Pharmaceuticals, opening up Hengrui's strategic layout in the field of intravenous general anesthesia, driving the growth of drugs stored in the research product pipeline, combining Hengrui's advantages in the field of inhalation anesthesia drugs, and integrating the entire product pipeline of intravenous/inhalation anesthesia. This is a pioneering drug. In spite of this, resmazolam tosylate, a "new drug" without compound patent, only relies on salt type patent as the first line of defense. It seems that it is not difficult to imitate strongly. Of course, it may also be because of its strong sales ability and the proportion of anesthesia market. Hengrui is not worried about the future trend of the product and the competition of its competitors, Whether it can be approved next and how the future road is worthy of continuous attention.