China Puts Renewed Focus on Monoclonal Antibodies in COVID-19 Fight
Amidst recent news that Pfizer is suing a former employee for stealing COVID-19 vaccine secrets come reports that researchers in China are busy developing several treatments, combining vaccines and drugs for COVID-19, and also working on monoclonal antibody treatments.
Pfizer employed Chun Xiao Li in 2006 as an associate director of statistics in its global product development group based in China. In 2016, Ms. Li transferred to Pfizer's facility in La Jolla, California. The lawsuit focuses on Pfizer's COVID-19 vaccine and its avelumab and elranatamab monoclonal antibodies.
On December 7, the two parties reached an accord where Pfizer's lawyers will review Li's computers and online accounts for confidential information. Li will then submit a confidential declaration stating that she no longer possesses Pfizer's confidential information or trade secrets.
Apart from intellectual property, the issue also highlights the importance and value of monoclonal antibodies (mAbs) as human therapeutic agents.
What are mAbs?
Given the impressive advances in biotechnology, mAbs are now becoming a major branch of therapeutics as they are shown to be effective in treating an ever-widening range of diseases.
mAbs are essential therapeutic biological products that are made in a laboratory to bind to a specific antigen. As part of its defense against foreign invaders, our immune system produces many antibodies, which are proteins that bind to specific targets inside the body, such as infection-causing antigens. When an antibody binds to an antigen, it activates the immune system, destroying the antigen-containing cells.
Currently, China has approved 21 mAb drugs (10 locally developed and 11 imported). Compared to the U.S. (0 months), the EU (8.9 months), and Japan (43.4 months), the median drug lag in the approval of 11 imported mAbs in China was 87.1 months, according to this report.
The emergence of new biopharmaceutical companies, the transformation of current drug companies and their shift to antibody therapy and the pooling of high-level talent contribute to mAb development in China. According to the study, various policies and incentives for attracting and retaining high-level talent have effectively addressed the lag of mAb drugs in China.
Brii Biosciences Leads the Way
Among drug producers in China, a neutralizing mAbs combination therapy called BRII-196/BRII-198 is expected to become the first in the country to get approval for market use in December. It's also likely to be the first to receive emergency use authorization in developed countries such as the U.S.
Researchers at Tsinghua University, the Third People's Hospital of Shenzhen, and Brii Biosciences have developed a combination therapy that has 78% effectiveness in reducing hospitalizations and death rates.
Brii has dual headquarters in China and the U.S. The therapy has already been adopted in the treatment of around 700 patients in China infected in the recent epidemic flare-ups caused by the Delta variant.
The two experimental mABs - BRII-196 and BRII-198 - demonstrated a statistically significant reduction of 78% in hospitalization and death in Phase III clinical trials conducted in the US, Brazil, South Africa, Mexico, Argentina and the Philippines.
The trial, known as ACTIV-2, was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). NIH's Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program is a public-private partnership to develop a coordinated research strategy for speeding the development of the most promising treatments and vaccine candidates.
China's Early Research in Response to the Pandemic
Chinese researchers began developing COVID-19 drugs as early as January 21, 2020. In response to the pandemic, China's Ministry of Science and Technology organized a special project for the R&D of medications, with a special working group set up less than a month later comprised of experts in related fields from across China.
The world's first clinical trial for the antibody on a healthy human participant after completing testing on non-human primates was conducted in China in June of 2020 when the first subject from the Shanghai-based Huashan Hospital of Fudan University received an injection of JS016.
JS016 has been approved for emergency use by 15 countries, with the combination of another neutralizing antibody. Co-developed by Junshi Biosciences and the Institute of Microbiology under the Chinese Academy of Sciences, it is recombinant and a mAb against COVID-19. The drug has commenced Phase III clinical trials overseas.
Another experimental drug has cut hospital stays. The drug, named DXP-604 and based on a neutralizing antibody, was developed by a research team led by Xie Xiaoliang, director of the Beijing Advanced Innovation Center for Genomics at Peking University.
Last year in June, China published a white paper on its fight against COVID-19, launching what it termed a "resolute battle to prevent and control its spread."
The white paper said China has succeeded in cutting all channels for the transmission of the virus but noted that the virus was currently wreaking havoc throughout the world.
That was June 2020. Since then, there have been 53 R&D emergency projects concerning clinical treatment and medications in China and about USD $49 million ($49,317,990) RMB 315 million in funds provided by the government.
Funding was also provided by CEPI, the Coalition for Epidemic Preparedness Innovations, when it partnered with Shanghai Zerun Biotechnology Co. and its parent company Walvax Biotechnology to advance the development of both COVID-19 prototype and variant vaccine candidates. CEPI will provide US$13.1 million to support Phase I clinical trial, process optimization and scale-up of the prototype vaccine, and preclinical studies and Phase I clinical trial of the variant vaccine.
Another innovative antibody developed by Boan Biotech, a holding subsidiary of the Luye Pharma Group, has gone into phase II clinical trials in China and many overseas countries and regions.
The company submitted an investigational new drug (IND) application for a self-developed drug LY-CovMab to the U.S. Food and Drug Administration this June. LY-CovMab is an investigational biological antibody for the treatment of COVID-19. Boan Biotech has been working on developing LY-CovMab since February this year.
Sinopharm, Sinovac and UAE
There are fresh doubts about China's vaccines. Though there has been a new uptick in COVID-19 cases in places with a high level of Sinopharm or Sinovac vaccinations, raising concerns that these vaccines may not be as effective as officials might have hoped, Sinopharm's COVID-19 drug is soon to be put into a clinical trial in the United Arab Emirates (UAE).
Early this month, the Chinese COVID-19 vaccine that completes dosage within a week was cleared for trial in the UAE as a preventive and therapeutic option. Since late 2020, all UAE residents and citizens have received the Sinopharm vaccine, one of the fastest vaccination campaigns in the world.
As part of a joint venture between Chinese pharmaceutical company Sinopharm and UAE-based tech company G42, the UAE will significantly expand vaccine access in developing countries. The UAE announced the beginning of production of the first indigenous COVID-19 vaccine in the region in March.
UAE and Bahrain residents who have already received two doses of Sinopharm are also being offered the booster shot.
Sinopharm was approved by the World Health Organization for emergency use in May, making it the first non-Western vaccine to be approved. China's state-owned China National Pharmaceutical Group (commonly called Sinopharm) developed it, and it is one of the country's two main vaccines that have been given to millions of people worldwide.
Sinopharm has developed two drugs for mild COVID-19 that are based on human immunoglobulin derived from convalescent plasma and mABs. In early September, Sinopharm unveiled four second-generation COVID-19 vaccines that target the Delta and Beta variants, belonging to three types: inactivated, recombinant protein and messenger ribonucleic acid (mRNA).
The focus of vaccination in China is to "prevent people from getting ill [because of COVID-19], but not from getting infected."
Incidentally, Sinopharm developed two vaccines via its subsidiary China National Biotec Group. The BIBP vaccine, developed via subsidiary Beijing Institute for Biological Products, had an efficacy rate of 79%. The vaccine secured WHO emergency approval, paving the way for its distribution via Covax, a WHO effort to share vaccines more equitably.
According to the WHO factsheet for the BIBP vaccine, the trial was not aimed at demonstrating efficacy against severe disease in comorbid people, or those over 60 years of age.
Sinopharm's other vaccine, developed via a Wuhan unit and not listed for emergency use by the WHO, has an efficacy rate of around 73%.
Continuous Development of Vaccines
In February 2020, a team of researchers at Tsinghua University in Beijing, led by Zhang Linqi, deciphered the structure of a part of the spike protein called the receptor-binding domain, which docks on ACE2 and causes infection. The findings were published in Nature in March.
Tsinghua University scientists Zhang and Wang isolated mAbs from a batch of convalescent patients in Shenzhen in collaboration with Zhang Zheng and Liu Lei from Shenzhen No 3 People's Hospital. The patients were a family cluster who traveled to Wuhan.
Since then, China has developed more vaccines and drugs based on antibodies, though the latter has been used for viral infections. Anti-SARS-CoV-2 mAbs have been approved by the US FDA for patients at various stages of the disease.
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