Tangning Tongluo Tablets Approved to Directly Conduct Phase III Clinical Trials

On November 12, Beletalent (ZHUHAI) Pharmaceutical Co., Ltd.（hereinafter referred to as Beletalent） received the “Notice of Approval for Drug Clinical Trial” approved and issued by the National Medical Products Administration, agreeing to conduct Phase III clinical trials of Tangning Tongluo Tablets, a Class 1.1 new Chinese medicine, for the treatment of diabetic retinopathy (DR).

This approval marks that Tangning Tongluo Tablets has become the first Class 1.1 new Chinese medicine since the implementation of the “Special Provisions on the Registration and Administration of Traditional Chinese Medicines” to directly enter Phase III clinical trials based on human use experience and exemption of Phase I and II clinical trials of traditional Chinese medicine preparations by medical institutions.Dramatically truncating the research and development cycle and hastening the progression of new drug commercialization, the maiden new drug variety declared by Beletalent has consummated an all-encompassing evidence chain integrating pharmacy, pharmacology, toxicology, and clinical practice. It is prognostically poised to obliterate the lacuna in the worldwide clinical pharmacotherapy of DR and stand out as a quintessential and triumphant paradigm in the conversion of traditional Chinese medicine preparations within medical establishments into novel traditional Chinese medicine medicines.This feat has not merely garnered acclaim and validation for the firm’s inventive prowess but has also robustly galvanized additional innovation.

Pre – clinical scientific research lays a solid theoretical foundation

Tangning Tongluo Tablets are a new type of traditional Chinese medicine developed by Guizhou Bailing for the treatment of type II diabetes and its complications during the long-term process of exploring and inheriting the treasure trove of ethnic medicine.

• In the safety evaluation test conducted by JOINN (Suzhou)of JOINN Laboratories, no obvious toxic reactions were found in the acute toxicity test of Tangning Tongluo, and the long-term toxicity test indicated that it is safe for clinical use.
• Main pharmacodynamic research results conducted by The Institute of Medicinal PlantDevelopmentshow that Tangning Tongluo can significantly reduce glycosylated hemoglobin levels, effectively reverse diabetic fundus lesions, delay and reduce DR, improve insulin resistance index, and reduce pancreatic islet β The degree of cell degeneration and necrosis.
• The University of Hong Kong conducted research on the mechanism of action of Tangning Tongluo. The final report clarified that Tangning Tongluo can significantly improve type I and type II diabetes and their complications, and its mechanism of action is related to anti-inflammatory targets. Relevant research results were published in the world’s top science and technology magazine “Science” sub-journals “Science Advances” and “Cell Communication and Signaling” in 2019. This is the first time that a Chinese Miao medicine has been published in an authoritative international academic journal. This research has discovered a new target for the treatment of diabetes and complications worldwide, opening up a new path for human treatment of diabetes and complications.

Standardize Clinical Trials to Accumulate Safe and Effective Case Records

Based on sufficient previous preclinical research, human clinical trials of Tangning Tongluo Tablets were carried out in an orderly manner. In three standardized clinical trials, the total drug exposure of Tangning Tongluo Tablets reached 300 cases (60 cases in the General Hospital of the People’s Liberation Army and 240 cases in two clinical studies of national projects), of which 120 cases were effective in the treatment of DR, further verifying the safety and effectiveness of Tangning Tongluo Tablets, and fully accumulating clinical trial data and practical experience that meet international standards, laying a solid foundation for the smooth implementation of subsequent Phase III clinical trials.

• In 2020, Tangning Tongluo completed human clinical trials at Chinese PLA General Hospital, proving that it can effectively lower glycated hemoglobin levels, and the extent of blood sugar reduction is comparable to the first-line alternative blood sugar-lowering medicinesin the “Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2017 Edition)”; among the secondary endpoints, the area under the C-peptide curve increased after 12 weeks of treatment with Tangning Tongluo, suggesting that it has a certain effect on the recovery of pancreatic beta cell function, and it has good safety and tolerability.
• In 2021, the project “Multi-center clinical study and mechanism exploration of Miao medicine Tangning Tongluo Tablets in the prevention and treatment of diabetes and retinal complications” was supported by the “Special Project for Scientific and Technological Research of Traditional Chinese Medicine” of the State Administration of Traditional Chinese Medicine. The project conducts clinical research on the treatment of prediabetes and diabetic retinopathy with Tangning Tongluo Tablets.
• In February 2024, the Tangning Tongluo series of national projects was successfully concluded and passed acceptance. Two clinical studies found that Tangning Tongluo Tablets can significantly reduce the risk of diabetes and the occurrence of DR in people with prediabetes and has good safety. No important known and potential risks were found; it is the only DR treatment approved for marketing. Compared with the chemical drug calcium dobesilate capsules, it can more effectively improve the best corrected visual acuity of patients with non-proliferative diabetic retinopathy, and is more effective in reducing fundus bleeding.

Extensive Clinical Application to Solidify the Advantage of Human Experience

As early as 2013, Tangning Tongluo Tablets was developed as a medical preparation in accordance with the “three-in-one combination” review evidence system and the “Medical Institution Preparation Registration Management Measures” (Decree No. 20 issued by the Bureau). In 2014, Tangning Tongluo Tablets obtained the “Medical Institution Preparation Registration Approval” issued by the Guizhou Provincial Food and Drug Administration and was put into clinical application in the form of a medical preparation.

At present, through building its own diabetes specialty hospitals and cooperating with authoritative medical institutions for joint research, Tangning Tongluo Tablets have obtained the “Medical Institution Preparation Registration Certificate” in five provinces and regions, including Guizhou, Hunan, Yunnan, Inner Mongolia and Guangxi, and have been successively included in the Guizhou Provincial Medical Insurance Catalog, the Guizhou Provincial New Rural Cooperative Medical Care Catalog, the Hunan Provincial Medical Insurance Catalog, etc.

So far, Tangning Tongluo Tablets has been used to treat about 627,000 patients with dysglycemia and complications of diabetes, and has accumulated a large amount of clinical data, clarified the scope of indications, and confirmed its positive effect on patients with diabetes, especially diabetic retinopathy. In addition, the company has also cooperated with the China Association of Handicapped Persons and Guizhou Disabled Persons Welfare Foundation to carry out public welfare activities, donating Tangning Tongluo Tablets to diabetic disabled people, while actively practicing social responsibility, further accumulating rich human experience.

Follow Policy Rhythm to Accelerate New Drug Application Process

In recent years, the state has vigorously supported the research and development of new traditional Chinese medicine medicines and proposed “an evaluation evidence system that combines traditional Chinese medicine theory, human experience and clinical trials” (referred to as the “three-in-one combination” evaluation evidence system). Article 23 of the “Special Provisions for the Registration Management of Traditional Chinese Medicine” issued in 2023 emphasizes that “for new traditional Chinese medicine medicines derived from clinical practice, if human experience can provide research and supporting evidence in terms of clinical positioning, screening of applicable population, exploration of treatment courses, exploration of dosage, etc., Phase II clinical trials may not be required.”

Leveraging the impetus of national policies and integrating the policy, resource, and geographical advantages of the Guangdong-Macao In-Depth Cooperation Zone in Hengqin, Beletalent concurrent with the further refinement of the technical aspects of the Tangning Tongluo Tablets project, on-site guidance and support have been procured from the Executive Committee of the Guangdong-Macao In-Depth Cooperation Zone, the Greater Bay Area Branch of the Center for Drug Evaluation and Inspection of the National Medical Products Administration, as well as the Guangdong-Macao Pharmaceutical Industry (Traditional Chinese Medicine Preparation Center of Guangdong-Macao Medical Institutions). This has fortified the quality of the dossier for the IND application of Tangning Tongluo Tablets in strict accordance with the stipulations of the “Special Provisions for the Registration Management of Traditional Chinese Medicine”, furnishing not only ample clinical research evidence but also a substantial body of non-clinical and pharmaceutical research outcomes. It has established a paradigmatic precedent for directly initiating Phase III clinical research for the conversion of traditional Chinese medicine preparations in medical institutions into new medicines under the national “three-in-one combination” principle and pursuant to Article 23 of the “Special Provisions for the Registration Management of Traditional Chinese Medicine”. This triumphant application also augments the prestige of the traditional Chinese medicine industry in Hengqin. The company will substantially curtail the R & D cycle, diminish R & D costs, and expedite the market entry of new medicines. Tangning Tongluo Tablets is anticipated to bridge the void in clinical medications for DR on a global scale and emerge as a paradigmatic and successful instance of the transformation of traditional Chinese medicine preparations in medical institutions into novel traditional Chinese medicine medicines.

Beletalent will perpetually intensify its endeavors in the exploration and innovation of pharmaceutical R & D, augment communication and interactions with drug regulatory administrations, ceaselessly impel the stable advancement of diverse R & D initiatives, and expedite the pace of new drug commercialization.