Developments and Critical Issues of COVID-19 Treatment/Vaccine R&D in China

New update:

It has been reported by the CPhI.CN on Aug. 18th that the COVID-19 inactivated vaccine production workshop of the Beijing Institute of Biological Products of Sinopharm Group has passed the joint biosafety inspection organized by the relevant national departments and has the conditions for use. With the price of two vaccinations being less than 1000 RMB, the protection could reach 100% according to the president of Sinopharm Group. The inactivated vaccine is expected to be marketed by the end of 2020, with the annual capacity of over 200 million.

It has been over half a year since the pandemic first outbroke in Wuhan of China. This article is to review and update what we know about treatments and vaccines development, and critical issues in the fight against the pandemic.

Until today, there is no specific treatment for disease caused by a novel coronavirus. However, many of the symptoms can be treated with existing drugs, some that showed early promise in the fight against the virus is now proved to have better clinical effect.

In April 2020, Gilead announced that the clinical study on patients with severe COVID-19 terminated early in China due to low enrollment. On July.9th, based on the research of Vanderbilt University Medical Center (VUMC) and Gilead Sciences, Remdesivir “potently” inhibited SARS-CoV-2 which causes COVID-19 in human lung cell cultures, though it has been given to patients hospitalized with COVID-19 on a compassionate use basis since late January and through clinical trials since February,  before the European Commission granted conditional marketing authorization for Veklury® (remdesivir) as a treatment for COVID-19 on July.3rd, and the Japanese Ministry of Health, Labour and Welfare (MHLW) granted regulatory approval for the drug on May.7th.

On April 14th, Yiling Pharmaceutical announced that its Lianhua Qingwen capsules and Lianhua Qingwen granules was granted approval to add functional indications for the drug to be used in the treatment of the conventional treatment of novel coronavirus pneumonia by State Drug Administration.

On July 1st, FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems; while WHO discontinues hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19.

Treatments Came to the Surface but the Vaccine Still in Developing

Different methods have been explored by drug-manufacturers and medical product suppliers in order to successfully develop a vaccine against the virus. According to the data collected by Milken Institute for Global Health, as of May. 9th, 2020, there have been 123 COVID-19 trials in various stage in the research pipeline which created at least 5 major race tracks: inactivated or weakened virus, recombinant subunit vaccine, nucleic acid, adenovirus vector vaccine, virus-like particles and others.

Back to 12 January, China shared the full RNA sequence of the novel virus, thus kicked off the competition of vaccine development in the fight against COVID-19. According to Ministry of science and technology, National Health Commission of China on June.19th, clinical trials have been carried out on 1 adenovirus vector vaccine, 1 recombinant subunit vaccine, and 4 inactivated vaccines, accounting for about 40% of the total number of vaccines in clinical trials worldwide. And based on what WHO expert disclosed at a press conference that a total of 17 COVID-19 vaccines have entered clinical trials.

Up until the publishing date of this article, only recombinant COVID-19 vaccine Ad5-nCoV, an adenovirus vector vaccine jointly developed by CanSino Bio and the Institute of Bioengineering, Academy of Military Medical Sciences has been approved for limited use in military of China. On July.21st, the company has reported through publishing early data in the journal The Lancet, that on Phase II trial of Ad5-nCoV in 508 patients, showed antibody and T-cell immune responses with no serious side effects.

Meanwhile, on July.16th, it was reported that Phase III clinical trials of the COVID-19 vaccine led by Chinese state-owned pharmaceutical company Sinopharm has begun in Abu Dhabi. It is the world’s first Phase III trial of an inactivated vaccine which are well known and have been used against diseases such as influenza and measles.

In addition to adenovirus vector vaccines and inactivated vaccines, China's first COVID-19 mRNA vaccine was also approved for clinical trials on June 26. It was jointly developed by The Academy of Military Medical Sciences (AMMS) of the PLA Academy of Military Science, Suzhou Abo Gen Biosciences and Yunnan Walvax Biotechnology Co., Ltd.

Critical Issues with the Vaccine Development and Product Supply

No matter which vaccines take the lead to be approved, manufacturers of the product shall be able to answer the question：how to ensure mass production capacity for the vaccine to be prepared for the mass market.

According to World Health Organization (WHO) on July.3rd, there may be candidate vaccines that will be effective against the novel coronavirus by the end of 2020. However, the question is whether the vaccine production capacity can keep up with demand. Truth is, not only the dosage of vaccination varies in using different kind of vaccines, it also matters in terms of the age of patients who receive vaccination.

Taking the bottles as an example, earlier attention has been focused on the bottles after media reported that there were only 200 million vaccine bottles left in the world, which might be not enough, and the bottle supply would not be guaranteed even if the vaccine was invented, reference to an article published on PharmaSources.com, “Will the Bottles be Enough with the Marketing of COVID-19 Vaccine?”.

Well, the future belongs to start preparing now.

On April 15th, Beijing Institute of Biological Products completed the country's first and only high-level biosafety production facility. Once being put into use, its COVID-19 vaccine production capacity will reach 120 million doses per year. And it’s not far away before the completion of the high-level biosafety production facilities of Wuhan Institute of Biological Products which will contribute an annual production capacity of 100 million doses.

In an interview with James Robinson, the biopharma executive of The Coalition for Epidemic Preparations (CEPI), who said CEPI has taken actions to ensure manufacturing capacity through the work with more than 200 biopharma or sterile vaccine production companies.

UK said it will provide 100 million pounds ($127 million) of funding for a facility to scale up the the manufacturing of COVID-19 vaccines.

However, multiple vaccinations are required for patients with inactivated virus vaccines which means a larger production capacity will be a big challenge in order to ensure mass production. With the advanced technology in developing inactivated virus vaccine, the production capacity is guaranteed and the quality standard is under control. And this has influenced US to choose to develop mRNA vaccines which can amplify and persistently express viral antigens in the body, activate the innate immune system, and do not require multiple vaccination.

Do you believe that a production capacity for billions of vaccine manufacturing is possible for a short period of time? Which vaccines mentioned above will eventually be produced to the hands of needs? How effective and safe it will be? Follow PharmaSources.com to get updated with the new developments of COVID-19 vaccines and more.

References:

https://qz.com/1854077/a-brief-overview-of-all-the-covid-19-vaccines-in-the-pipeline/

https://www.reuters.com/article/us-health-coronavirus-cepi-vaccines-excl/exclusive-vaccine-alliance-finds-manufacturing-capacity-for-4-billion-doses-of-coronavirus-vaccines-idUSKBN23V3D0

Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial

Gilead Sciences Statement on Data From Remdesivir Study in Patients With Severe COVID-19 in China

Gilead Announces Approval of Veklury® (remdesivir) in Japan for Patients With Severe COVID-19

European Commission Grants Conditional Marketing Authorization for Gilead’s Veklury® (remdesivir) for the Treatment of COVID-19

Lianhua Qingwen capsule included in Beijing’s COVID-19 treatment program

More sources such as official website, media reports that can be searched from the internet.

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