Speakers

Biography

Qi Li, MD in Respiratory Medicine, is currently employed as an attending physician in the Tuberculosis Department of Beijing Chest Hospital, affiliated with Capital Medical University. I am now a visiting scholar in the Department of Infectious Diseases at the University of Pittsburgh. I have applied for and led two projects and published over ten articles in both Chinese and English. I have participated in more than ten clinical studies on tuberculosis drugs and innovative tuberculosis diagnostic technologies. As one of the editors, I wrote the second edition of Modern Tuberculosis (People's Health Publishing Press), published in February 2022. I successfully applied for the "Rong Hong Plan" talent program at Beijing Chest Hospital in May 2023. In December 2023, I was elected as a tuberculosis professional member of the Beijing Institute of Chronic Diseases and Health Education.

Abstract

In the world, tuberculosis (TB) is the second largest infectious killer after COVID-19 (surpassing AIDS). However, the incidence rate of multidrug-resistant tuberculosis has increased year by year, and only about two-fifths of drug-resistant tuberculosis patients have received treatment. The current situation of anti-TB treatment in China is that MDR/RR burden ranks second in the world, second-line drugs are expensive, have poor accessibility, low detection and inclusion rates, and low treatment success rates. At present, there are few new drugs for drug-resistant tuberculosis, and no new class I anti-TB drug produced in China has been approved. Therefore, there is an urgent need for the application of new drugs and strategies for drug-resistant TB. The status of Global and Chinese research and development of anti-TB drugs is that 28 anti-TB drugs have entered clinical trials worldwide before September 2023. In China, Pretomanid has entered the Phase I clinical trial, QTB-658, JDB-0131, and Pifazimine have entered the Phase II clinical trial, and Shudapyridine has entered the Phase III clinical trial. Shudapyridine is the first drug for class I anti-TB drug under development in China to treat drug-resistant pulmonary TB and the first drug-resistant pulmonary TB drug in China to enter clinical stage III.

Shudapyridine exerts its anti-Mycobacterium tuberculosis (MTB) effect by inhibiting the synthesis of adenosine triphosphate (ATP) in MTB. In vitro, pharmacological studies on Shudapyridine have shown that WX-081 has comparable efficacy to Bedaquiline (BDQ) in various clinical MTB strains and mouse TB infection models. Preclinical safety and pharmacokinetic studies have shown that WX-081 is safer than BDQ and has no Q-T interval prolongation side effects. The PK properties of WX-081 are superior to BDQ, with a higher lung/blood ratio (6X). The Phase I clinical trial showed good tolerability of WX-081, and no subjects experienced Q-T interval prolongation. It is recommended to take it with meals or with meals. The pharmacokinetic properties are excellent, and the exposure level linearly depends on the dose. At the same dose, the maximum blood drug concentration (Cmax) is 1.3-1.5 times higher than that reported in the literature of BDQ. Phase II clinical trials have shown that WX-081 exhibits good efficacy and safety in early bactericidal activity, safety and tolerability, and preliminary efficacy in patients with drug-sensitive and drug-resistant pulmonary tuberculosis. The Phase III clinical study is a randomized, double-blind, positive drug control study aimed at the safety and efficacy of rifampicin-resistant pulmonary tuberculosis patients. Currently, 19 centers in China are participating, and as of the end of 2023, 220 subjects have been enrolled. In addition, we found that SPaL therapy had a slightly better anti-TB effect than BPaL therapy in the BALB/c mouse models of pulmonary TB. In conclusion, WX-081 is expected to make achievements in treating drug-resistant TB.