The battle against tuberculosis: from Delamani, Bedaquinoline, Pretomanid to my country's first self-developed Serdapyridine

In 2020, the multi-drug resistant tuberculosis drug bedaquiline fumarate (hereinafter referred to as "bedaquiline") will be launched in China
.
Bedaquiline is recognized by the WHO as the drug of choice for the treatment of multidrug-resistant tuberculosis.
This drug is the latest achievement of global tuberculosis drug research and development in the past half a century.
It was approved by the US FDA in December 2012 and approved by the U.
S.
FDA in 2016.
It was approved for listing by China’s National Food and Drug Administration on November 23, 2020, and was officially listed in China on January 2, 2020
.
Bedaquinoline is suitable for the treatment of multidrug-resistant tuberculosis in adults ≥18 years of age.
It can only be used when other tuberculosis drugs cannot constitute an effective treatment plan
.
At present, China has taken more than 400 patients with bedaquiline, 82 of which have completed 6 months of treatment, and the imaging results are significant, and the negative conversion rate of sputum bacteria at the end of June exceeds 80%
.

After the introduction of the two new drugs, Bedaquinoline and Dramani, some drug-resistant patients have begun to use these two drugs, and the cure rate is as high as 85%
.
In the study of Bedaquiline and delamanid in combination for treatment of drugresistant tuberculosis, researchers showed a cohort report, from January 2016 to August 2016, a total of 28 cases of multi-drug resistant tuberculosis from Armenia, India and South Africa The patient was treated with Bedaquinoline combined with Dramani
.
The median treatment time was 12 months, and 17 cases (61%) had combined treatment for more than 6 months
.
Among these 28 patients, 13 patients (46%) recovered or completed treatment, 5 patients (18%) died, 5 patients (18%) were lost to follow-up, 4 patients (14%) failed treatment, and 1 patient (4 %) was transferred
.

Although the results of this study show that the efficacy of Bedaquinoline combined with Dramani in the treatment of patients with multi-drug-resistant tuberculosis is not significantly better than that of Bedaquinoline monotherapy, the combined regimen of Bedaquiline-Dramani is mostly used For patients with poor prognosis (previous treatments are ineffective and/or tolerant to more than 5 drugs), the conversion rate of sputum culture is not inferior to that based on bedaquiline, and a good prognosis can be obtained
.
In addition, Bedaquinoline combined with Dramani has good safety
.

All in all, for patients with drug-resistant tuberculosis, the long-term safety of the Bedaquinoline-Dramani combination regimen is relatively good.
For patients with poor prognosis or multi-drug resistance, Dramani may be a good option.
An effective adjuvant drug, combined with Bedaquinoline, is used to select limited drug-resistant tuberculosis patients, providing a glimmer of hope
.

2020 "Nobel Prize in Pharmaceutical Industry" Best Drug Award: Pretomanid , a new molecular entity developed by its non-profit organization Global Tuberculosis Drug Development Alliance (TB Alliance), combined with bedaquinoline and linezolid to treat specific high resistance Medicine for pulmonary tuberculosis (TB) patients
.
It was launched in 2019.
It is the third new anti-tuberculosis drug approved by the FDA in the past 40 years and the first new TB drug developed and marketed by a non-profit organization
.

In a pivotal clinical trial, 109 patients with extensively drug-resistant TB and multi-drug resistant patients who were intolerant or unresponsive to existing therapies received a combination therapy consisting of Pretomanid, bedaquinoline and linezolid Treatment
.
The test results showed that after 6 months of treatment, the success rate of this combination therapy reached 89%, which was significantly higher than the historical success rate of treating patients with extensively drug-resistant TB
.

China is also one of the countries with a high burden of tuberculosis
.
According to the "Global Tuberculosis Report 2018" released by the WHO last year, there were estimated to be more than 10 million tuberculosis patients worldwide in 2017.
Among them, there were nearly 900,000 tuberculosis patients in China, nearly 40,000 deaths, and 73,000 drug-resistant tuberculosis patients, accounting for the global total.
13.
1% of the total, ranking second among the 30 countries with a high burden of tuberculosis
.

With the listing of Bedaquinoline, Dramani and PA824, but they are all developed by foreign pharmaceutical companies, they cannot fully meet the needs of China's tuberculosis, especially drug-resistant tuberculosis patients
.
In order to speed up the research and development of anti-tuberculosis drugs in China and improve the ability and level of control of the tuberculosis epidemic in China, in December 2020, China's self-developed class 1.
1 innovative drug in the field of tuberculosis (WX-081) has completed preclinical development and Clinical Phase I study, Phase I clinical results showed good safety tolerance to healthy subjects, excellent pharmacokinetic characteristics, and entered the Phase II clinical trial stage
.
The phase II clinical trial aims to explore the early bactericidal activity (EBA), safety and preliminary effectiveness of Serdapidine (WX-081) in pulmonary tuberculosis patients, and to provide sufficient evidence and basis for further clinical trials
.

This indicates that China’s first new anti-tuberculosis drug will be expected to provide TB patients, especially drug-resistant TB patients, with self-developed and more high-quality and low-cost therapeutic drugs, improve the quality of life of patients, and reduce the burden on patients.
Contribute to the world's tuberculosis prevention and control work
.

references:

[1] Guo Xueli, Ma Xiaoxue, Chen Huijuan, et al.
Analysis of characteristics and treatment of 1446 patients with multi-drug resistant tuberculosis[J].
Modern Preventive Medicine, 2021, 48(15): 2835-2839.

[2] Li Jinmeng, Yang Gaoyi, Cai Qingshan, et al.
Safety, efficacy, and serum concentration monitoring of bedaquiline in Chinese patients with multidrug-resistant tuberculosis [J].
International Journal of Infectious Diseases, 2021, 110: 179-186.

[3] Oelofse S, Esmail A, Diacon AH, et al.
Pretomanid with bedaquiline and linezolid for drug-resistant TB: a comparison of prospective cohorts[J].
The international journal of tuberculosis and lung disease: the official journal of the International unio against Tuberculosis and Lung Disease, 2021, 25(6): 453-460.

[4] Deng Qi, Xiao Chunling.
Research progress of new anti-tuberculosis drugs[J].
Chinese Journal of New Drugs, 2019, 28(13): 1567-1573.