Domestic Leading Vaccine Manufacturers Competiting to Upgrade R&D under COVID-19

2021-11-12 Source:Healthcare Executive

Since the outbreak of COVID-19, vaccination has been generally accepted as the most economical and most effective measure for prevention. For domestic vaccine R&D and manufacturing enterprises, this means an all-round competition of R&D and industrialization capabilities—who masters the hardcore technology, scales up R&D achievements quickly and smoothly, wins the race against time to stop the spreading of virus, and becomes the leader of vaccine.

Domestic vaccine technology reaching advanced international level with independent R&D of mRNA vaccine

There is a saying within the industry that goes like this: “Whoever wins the mRNA competition rules the industry.” Since the pandemic outbreak, major domestic vaccine manufacturers have been racing to develop mRNA technology—one of the world’s top technologies acclaimed as the “pearl of the crown.” At present, out of the many domestic enterprises engaged in the R&D of mRNA COVID-19 vaccines, only 3 have obtained clinical trial permission. Among them, the mRNA COVID-19 vaccine developed through cooperation between Walvax and Abon has entered Phase III clinical trial stage. After its acquisition of LIVERNA, AIM Vaccine has accelerated the R&D of mRNA COVID-19 vaccine, and Phase I clinical trial has shown high safety. This signifies that the technological level of domestic vaccine enterprises is approaching international advanced level.

The great change in the vaccine industry triggered by mRNA technology is worth looking forward to, but its application should not be confined to coronavirus—it may also offer a breakthrough for gene therapy in gene delivery technology. All of this indicates that the era of gene technology (mRNA technology) has arrived. In the future, mRNA technology is expected to fulfil its potential in the prevention of more infectious diseases, and even offer new therapies for cancer.

In a paper published in Nature, Prof. Drew Weissman mentioned that mRNA vaccine could simulate the natural infection process of virus to activate the immune system, and possibly trigger more powerful immune responses; multiple mRNAs can be packed in the same vaccine to improve vaccine applicability; the discovery and production of mRNA vaccine is more rapid compared than protein vaccine, hence a quicker response to sudden epidemic outbreak; and the same manufacturing steps and facilities can be used for different mRNA vaccines. As a result of these unique advantages, mRNA vaccine is developing at an astounding speed. Currently, in addition to various mRNA COVID-19 vaccines, mRNA vaccines for infectious diseases such as rabies and Zika virus, cancers, autoimmune diseases, and rare hereditary diseases are also under research.

From the R&D planning of major domestic vaccine manufacturers, we can see a clear picture of the application prospect of mRNA vaccines. AIM Vaccine disclosed in its prospectus that the focuses of its R&D plan include second-generation mRNA COVID-19 vaccine, mRNA rabies vaccine and mRNA RS virus vaccine, all of which are under research.

Polysaccharide conjugate vaccines entering the market successively as global best sellers

At the same time, major domestic vaccine enterprises have also made continuous breakthroughs in other advanced technology roadmaps. For example, many best-sellers have emerged from polysaccharide conjugate vaccines prepared through covalent bonding between bacterial polysaccharides and proteins.

Right now, the pathogenic bacteria of many common diseases around the world, such as pneumococcus and meningococcus, all have a layer of special structure called capsule, which is an ideal antigen for vaccine due to its good immunogenicity. Polysaccharide vaccines are manufactured by extracting the capsular polysaccharides of bacteria through a series of purification processes. However, since the polysaccharide vaccines function by producing antibodies via humoral immune response mediated by B cells within the human body, they cannot be used in infants (under 2 years of age) of weak B cell antibody production capacity and population with partial immunodeficiency.

Given that, polysaccharide conjugate vaccines are developed through technological upgrade on the basis of polysaccharide vaccines. By covalently binding capsular polysaccharides to protein carriers, they activate helper T cells to induce cellular immunologic response from the body, thus overcoming the age limitation of polysaccharide vaccines and prolonging the duration of immunization. Since the first polysaccharide conjugate vaccine obtained approval for the American market in the 1980s, various polysaccharide binding technologies have gained rapid development, and become one of the research priorities of the global vaccine industry. Meanwhile, the replacement of conventional polysaccharide vaccines with conjugate vaccines for certain diseases has been promoted in many countries including the US.

In the domestic market, polysaccharide vaccines still account for the majority of relevant technology products, while advanced polysaccharide conjugate vaccines are monopolized by various multinational pharmaceutical companies. Thus, domestic vaccine enterprises have been increasing their efforts to research and develop such innovative vaccine products. In 2020, the monopoly was broken by the 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) of Walvax Biotechnology. Later, in this October, AIM Vaccine, China’s No.1 private-owned vaccine industrial group, announced the R&D progress of its two best sellers one after another—PCV13 and ACYW135 meningococcal polysaccharide conjugate vaccines (i.e., MCV4).

For a long time, PCV13 has always been the world’s top-selling vaccine type, and referred to as the “king of vaccines.” In 2020, the sales of Pfizer’s Prevnar13 reached 5.85 billion US dollars, ranking first among vaccines around the world, far higher than the sales of the HPV vaccine in the second place (3.938 billion US dollars).

Currently, only three domestic enterprises have obtained approval for their PCV13 products. Pfizer’s Prevnar13 has been approved for the Chinese market in November 2016 and gone on sale in 2017 at an exorbitant price as an imported vaccine, with an annual lot release amount of merely 4 million doses, which however failed miserably at meeting the demand of the domestic market. In early 2020, the 13-valent pneumococcal vaccine (WEUPHORIA) of Walvax obtained approval and went on sale in the same year, with a designed production capacity of at least 30 million doses/year. However, throughout 2020, the lot release amount of Pfizer and Walvax’s PCV13 was 6.42 million doses and 4.47 million doses, which together could only meet the vaccination demands of only 1/4 of newborn infants in China. Meanwhile, BIOKANGTAI has only just obtained approval on October 22, its products still unavailable in the market. Besides, only 5% of Chinese children aged under 6 have been vaccinated with PCV13, which is far below the coverage of 81.4% in the US, suggesting that there is still enormous room for improvement.

On October 14, AIM Vaccine’s PCV13 obtained ethical approval for Phase III clinical trials from the Ethics Committee for Vaccine Clinical Trials of the Yunnan Provincial Center for Disease Prevention and Control. This marks the beginning of Phase III clinical trials of PCV13, which is expected to achieve commercialization by 2024.

With its technology platform advantages, seamless project advancement capability and industrialization strength, AIM Vaccine guarantees the R&D, production and quality control level of PCV13.

Regarding product quality, animal test data shows: in a comparison of antibody level of 13 serotypes, AIM Vaccine’s PCV13 has 10 serotypes which demonstrate better immunogenicity than imported vaccines. Meanwhile, AIM Vacin has completed the reconstruction and upgrade of its pneumococcal vaccine production line, with a designed annual production capacity of 47 million doses. After realizing mass production, its product may actually satisfy the vaccination demands of newborns.

MCV4 is mainly used to prevent infection of meninges caused by Neisseria meningitidis, which could be lethal timely treatment, with a mortality rate of 20%-35%. According to data of the CDC of the United States, the incidence rate of meningococcal disease caused by Neisseria meningitidis is the highest among infants under 12 months of age and elderly people. Therefore, the best time for vaccinating infants with meningitis vaccine is under 12 months.

Neisseria meningitidis has 13 common clinical serotypes, among which A, C, W135 and Y are the most common pathogenic serogroups. At present, only three transnational pharmaceuticals have obtained approval for their MCV4 products. In the domestic market, the quadrivalent meningococcal vaccine with the widest serogroup coverage is MPSV4 (polysaccharide vaccine), which is not suitable for infants under 2 years of age. For them, the available vaccines are only group A meningococcal polysaccharide vaccine (MPSV-A) and group A and C meningococcal polysaccharide conjugate vaccine (MCV-AC), which however cannot really establish comprehensive protection.

Therefore, MCV4 products which can offer comprehensive protection for infants under 2 years of age have huge market potential. According to the data of China Insights Consultancy, the compound annual growth rate of China’s meningococcal vaccine market may reach 11% between 2020 and 2030. Also, Sinolink Securities estimated that the average gross margin of MCV4, a blockbuster product, will be around 90% upon entering the market.

With its clinical trial application accepted and under review by the Center for Drug Evaluation, NMPA, AIM Vaccine’s independently researched and developed MCV4 has officially entered the review stage, while continuing to pioneer innovation and R&D of the vaccine industry.

it's worth noting that AIM Vaccine has always been a major domestic supplier of MPSV4, with multiple key quality indicators of its products higher than various standards. For instance, the O-acetyl, distribution of molecular sizes and bacterial toxoid content of the capsular polysaccharides of group A, C, Y and W135 meningococcus are all batter than the specifications in Chinese Pharmacopoeia, European Pharmacopoeia and WHO regulations. Quality products reflect the leading technology and technological strength of an enterprise, which is also an important prerequisite for guaranteeing the continuance of the high quality standards of MCV4.

At the industry level, vaccine R&D and production have posed higher technological requirements for pharmaceuticals, and the cutting-edge polysaccharide-protein conjugation technology has further more raised the threshold of enterprise competition. At present, only a few leading vaccine enterprises in China have made significant progress in products with this technology roadmap.

The two vaccines of AIM Vaccine with progress both utilize multiple highly sophisticated technologies involving the conjugation of polysaccharides and carrier proteins. According to information, on the foundation of its existing technologies of polysaccharide antigen extraction and purification, AIM Vaccine has developed a carrier protein production technology based on TT and CRM197 carrier proteins. Meanwhile, with its significant advantages on the strength of the whole industry chain and a big platform, AIM Vaccine can also realize large-scale production capacity release and guarantee market supply after obtaining approval for the market.