Source of enterprise announcement: State Food and drug administration, tengshengbo pharmaceutical, Tsinghua University
Guide: China’s first self educated intellectual property COVID-19 neutralizing antibody combination therapy.
In the evening of December 8, 2021, the official website of the State Administration of drug administration announced that the application of COVID-19 neutralization antibody combined with BRII-196 and BRII-198 was registered by the State Administration of drug administration. It is China’s first self educated intellectual property COVID-19 neutralizing antibody combination therapy.
According to the relevant provisions of the drug administration law, the State Food and drug administration shall carry out emergency review and approval according to the special approval procedures of drugs, and approve the combination of the above two drugs for the treatment of light and ordinary adults and adolescents (12 to 17 years old, weighing more than 40kg) with New Coronavirus infection (COVID-19) who are highly risk factors (including hospitalization or death). Among them, adolescents (12-17 years old, weight ≥ 40kg) with indications are subject to conditional approval.
BRII-196/BRII-198 combined therapy was led by Professor Zhang Linqi, director of the center for comprehensive research of AIDS and global health and infectious disease research center of Tsinghua University School of medicine and Tsinghua University. Tengsheng pharmaceutical was promoted in collaboration with Tsinghua University and the third people’s Hospital of Shenzhen. The treatment proved effective anti COVID-19 drugs through a strictly randomized, double-blind, placebo-controlled study. Meanwhile, the approval marks the first self developed R & D in China and has proved effective anti COVID-19 specific drugs through a strictly randomized, double-blind, placebo-controlled study.
Professor Zhang Linqi said: “The approval of ambacizumab / romistimub combination therapy has brought the first new crown treatment specific drug to China. This combination therapy has shown excellent safety and protection in the international multicenter trial. It is the only antibody drug in the world that has carried out the evaluation of the treatment effect of people infected with variant strains and obtained the best data. This antibody combination therapy is the best for me China has provided a world-class treatment for COVID-19. It fully demonstrated the deep accumulation and technical reserves of Tsinghua University in the field of fighting against infectious diseases, and the ability and ability to call it to come, to fight, to fight and to fight. It has made important contributions to the epidemic prevention and control work in China and even in the world. We are very honored to be on the basis of the third people’s Hospital of Shenzhen and Tengsheng Bo medicine. High quality cooperation in, clinical and transformation research has made this landmark achievement. In the next step, we will continue to study the preventive role of monoclonal antibody combination therapy in high-risk and immune deficiency groups. ”
This approval was based on the phase 3 clinical trial of activ-2 supported by the National Institutes of Health (NIH), including the positive interim and final results of 847 enrolled patients. The final results showed that ambavizumab / romistuzumab combination therapy could reduce the risk of hospitalization and death of high-risk new crown outpatients by 80% (interim results were 78%) compared with placebo , which was statistically significant. As of the clinical end point of 28 days, there were no deaths in the treatment group and 9 deaths in the placebo group, and its clinical safety was better than that in the placebo group. At the same time, whether the treatment was started in the early stage (within 5 days after the onset of symptoms) or in the late stage (within 6 to 10 days after the onset of symptoms) Of the subjects, hospitalization and mortality were significantly reduced, which provided a longer treatment window for patients with new crowns.
In less than 20 months, Tsinghua University, in cooperation with Shenzhen Third People’s Hospital and tengshengbo pharmaceutical, rapidly promoted ambacizumab / romisvir combination therapy from the initial neutralizing antibody separation and screening to the completion of international phase 3 clinical trial, and finally obtained China’s listing approval. This achievement is the joint efforts of China and world-class scientists and clinical researchers The results include the support of the ACTIV-2 International Clinical Research Institute, the National Institute of allergy and infectious diseases (NIAID) of the National Institutes of Health (NIH), and the ACTIV-2 clinical trial team (ACTG), which leads clinical research.
Liu Lei, director of the clinical research center for infectious diseases in Shenzhen and Secretary of the Party committee of the third people’s Hospital of Shenzhen, said: “From the outset of the epidemic, we set the goal of technology epidemic prevention. Our team successfully extracted a pair of highly active neutralizing antibodies from the serum of the new crown rehabilitation patients, laying a solid foundation for the subsequent development of this anti COVID-19 drug. We are very pleased to work with Professor Zhang Linqi and Tengsheng pharmaceutical company of Tsinghua University to make China’s first new anti crown. Viral drugs contribute wisdom and experience. We hope that with the joint efforts of the vast number of research workers and medical workers, we can defeat COVID-19 as soon as possible.
Luo Yongqing, President and general manager of Greater China, said: “We are excited to achieve this important milestone and are working hard to promote the accessibility of this combination therapy for Chinese new crown patients. This achievement proves that we have been firmly committed to accelerating global innovation in the field of infectious diseases and filling unmet medical needs with efficient, scientific, rigorous and excellent results. As a multinational company operating in China and the United States Biotech Corp, I am proud of Tengsheng Bo’s drug achievement, and we spare no effort to help China cope with the complex COVID-19 needs scientifically, and meet the clinical needs of our new champions.
About ambacizumab / romistuzumab
(previously brii-196 / brii-198)
The monoclonal antibody to the monoclonal antibody and the roomsway monoclonal antibody is a non competitive new-type severe acute respiratory syndrome virus 2 (SARS-CoV-2) obtained from the third people’s Hospital of Shenzhen and Tsinghua University in the rehabilitation period of New Coronavirus pneumonia (COVID-19). Monoclonal neutralizing antibodies, especially bioengineering technology, are used to reduce the risk of antibody mediated dependent enhancement and prolong the plasma half-life to obtain more lasting therapeutic effects.
In October 2021, tengshengbo pharmaceutical has completed the application for emergency use authorization (EUA) of ambacizumab / romistuzumab combination therapy to the U.S. Food and Drug Administration (FDA).
In addition, tengshengbo is actively promoting the application for registration of ambacizumab / romisizumab combination therapy in other mature and emerging markets around the world, first ensuring market access in countries that have conducted clinical trials and countries that have a huge gap in access to efficient treatment. Tengshengbo will also carry out further research in China to evaluate ambacizumab/ Prophylactic and immunopotentiating effects of combined therapy with romisvir mAb in immunosuppressed population.
For the “delta” in China COVID-19, Tengsheng Bo, which was caused by the mutant strain, donated nearly 3000 people’s total of nearly two million people from the Guangdong Province, Yunnan Province, Jiangsu Province, Hunan Province, Henan Province, Fujian Province, Ningxia autonomous region, Gansu Province, the Inner Mongolia Autonomous Region, Heilongjiang Province, Qinghai Province, China Province and the province in June 2021. , nearly 900 patients were treated, which is the largest number of patients with neutralizing antibodies in a single country. A large number of health care professionals gained experience and confidence in using this combination therapy and made great contributions to combating the epidemic.
About activ-2 trial phase 3
The marketing approval of ambacizumab / romistuzumab combination therapy by China Drug Administration (nmpa) is based on the activ-2 trial (nct04518410) supported by the National Institutes of Health (NIH) Interim and final results of phase 3. The final results showed that compared with placebo, this combination therapy reduced the composite end point of hospitalization and death of covid-19 outpatients at high risk of clinical progression by 80%, which was statistically significant. As of the 28 day clinical end point, there were no deaths in the treatment group and 9 deaths in the placebo group. No new safety hazards were observed.
The interim results published on October 4, 2021 showed that ambacizumab / romisizumab combination therapy reduced the composite end point of hospitalization and death of covid-19 outpatients at high risk of clinical progression by 78% compared with placebo, which was statistically significant (unadjusted, one-sided test p value < 0.00001) 2% (4 / 196) of the subjects who received ambacizumab / romisizumab combination therapy within 5 days after symptom onset progressed to hospitalization or death, compared with 11% (21 / 197) in the placebo group. Similarly, 2% (5 / 222) of the subjects who received ambacizumab / romisizumab combination therapy 6 to 10 days after symptom onset The rate of progression to hospitalization or death was 11% (24 / 222) in the placebo group. The analysis also showed that there were no deaths in the treatment group within 28 days, while there were 8 deaths in the placebo group. In the ambacizumab / romistumab combination therapy group, the adverse events (AE) of grade 3 or above were less than those in the placebo group, which were 3.8% (16 / 418) and 13.4% (56 / 419), respectively , no drug-related serious adverse events (SAE) or infusion reactions were observed.
The study was carried out in several clinical trial centers around the world, including the United States, Brazil, South Africa, Mexico, Argentina and the Philippines. The study included patients enrolled in the global rapid emergence period of sars-cov-2 variants from January to July 2021. As part of this study, the clinical efficacy data of ambavizumab / romisizumab combination therapy will also be based on the type of viral variants Evaluation. The current in vitro chimeric virus test data show that the combination therapy of ambacizumab / romistumab maintains neutralizing activity against the major sars-cov-2 variants of great concern, including b.1.1.7 (“alpha”), b.1.351 (“beta”), P.1 (“gamma”), b.1.429 (“epsilon”), b.1.617.2 (“Delta”) , ay. 4.2 (“delta +”, Deltaplus), c.37 (“ramda”, lambda) and b.1.621 (“Miao”, mu). Testing for the b.1.1.529 (Omicron) variant is currently in progress.
Post time: Dec-10-2021