How far behind is the vaccine industry?

Almost all pharmaceutical annual strategies are looking forward to the launch of a live attenuated shingles vaccine.

Just like a joke, the only blockbuster new product of domestic conventional vaccines in 2023 is still following the previous generation technology of 15 years ago and belongs to the me-worse variety.

This is a microcosm that the domestic vaccine industry is still stepping on the mud of me-worse.

Innovative drug Biotech has the ability to impact the old pattern, but emerging vaccine companies are small and mediocre, bringing more involution than iterative innovation to the industry.

The anti-epidemic situation is grim, and domestic vaccines still need to be worked on.

 01 

5 major varieties are absent

In 2021, the sales of the world's top ten vaccines (excluding new crown vaccines) totaled 23.91 billion US dollars, occupied by the four multinational giants Merck, Pfizer, Sanofi and GSK, of which 5 varieties (approved as early as 2005), domestic vaccine companies still have not been able to imitate and market.

Not to mention the source of innovation, it is difficult to follow.

4-valent/9-valent HPV vaccine: Wantai Biotech, Watson Biotech, Bowei Biotechnology, Connaught Guard, and Rico Biotech 9-valent HPV vaccine have all entered the phase III clinical stage. Wantai Biotech has the fastest progress, the phase III clinical trial and industrial scale-up of the 9-valent HPV vaccine are progressing smoothly, and the head-to-head clinical trial with Jiadaxiu 9 has completed the clinical trial site and specimen testing, and completed the construction of a commercial production workshop, with a production capacity of 60 million doses. As soon as 2024, the first domestic 9-valent HPV vaccine is expected to be on the market.

Quintuple/Six: Quintuple vaccine is used to prevent invasive infections caused by diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b, and can reduce the number of vaccination doses from the routine 12 doses in the national immunization schedule to 4 shots, improve infant vaccination compliance, and reduce the incidence of adverse reactions. Kangtai Biotech Quintuple obtained clinical approval in December 2020, and is the only domestic quintuple seedling that has obtained clinical approval, and is still preparing for clinical trials, which is still far from breaking Sanofi's monopoly.

Quadruple seedlings of mumples and gills: There is no quadruple seedlings of mumps and cheeks and chickenpox seedlings on the market in China. The clinical applications of Tiantan Biotechnology and Shanghai have not been approved, mainly related to the vaccination process. Kangtai Biotech will carry out the clinical application of the quadruple seedlings of mumps-chickenpox after completing the research and development of the corresponding single seedlings.

Group B brain vaccine: No group B brain vaccine has entered the clinical research stage or been approved for marketing in China. Zhifei Bio recombinant meningococcal type B vaccine was declared for clinical trial in September this year. Chengda Biologics and CanSino Biologics B group flow brain vaccines are undergoing preclinical research.

Shingrix and Zostavax product comparison

 02 

Obsolete technology

The clinical progress of Changsheng Bio's live attenuated shingles vaccine was once one of the fastest in China, and after three auctions, it dropped from 156.79 million yuan to 78.39 million yuan.

At that time, the head of medicine of an investment institution commented: Compared with the GlaxoSmithKline shingles vaccine, the technical gap between the two is like the difference between non-smartphones and smartphones.

Shingles, commonly known as snake waist wrapping, has 1.56 million new cases over 50 years old every year, and the pain in the onset of the disease is even no less than that of childbirth, and it will be accompanied by knife cuts, fire, electric shocks, and whipping sensations.

There are two technical routes for the herpes zoster vaccine. Merck Zostavax, a live attenuated vaccine for herpes zoster, was launched in 2006 with a protection rate of only 69.8% in the elderly population aged 50-59 years, and has been discontinued due to low prevention effectiveness and weak market competitiveness. In June 2019, GlaxoSmithKline's (GSK) recombinant shingles vaccine Shingrix was first launched in China, reducing the risk of herpes zoster infection in the elderly aged 50 years and above by 97.2%.

Baike Biotechnology, which is located in the northeast with Changsheng Biotechnology, is still the live attenuated vaccine route, and the shingles vaccine is in the supplementary stage and is expected to be launched early next year.

GlaxoSmithKline Shingrix costs as much as 1600 yuan / dose, and it costs 3200 yuan to receive two doses. The elderly group is price-sensitive, and the phase II clinical data of Baike Bioherpes zoster attenuated live disease show good safety and immunogenicity, with no weaker effectiveness than Zostavax, and significantly higher safety than Shingrix.

According to Frost & Sullivan, the market size of herpes zoster vaccine in China will reach 28.1 billion yuan in 2030. Domestic enterprises with recombinant protein shingles vaccine include Rico Biotechnology, Yidao Biotechnology, Luzhu Biotechnology, and Zhonghui Yuantong, of which Luzhu Biotechnology has entered the second stage of clinical research and development.

Watson Bio is developing the third generation of shingles vaccine, the shingles mRNA vaccine.

 03 

Total innovation anxiety

Aygen Biosciences, founded in early 2019, was once the brightest star of vaccine Biotech, raising more than US$700 million in Series C financing in August 2021, setting a new record for a single financing before the IPO of a local pharmaceutical company. At that time, it was the beginning of the bursting of China's biotechnology bubble, and Aygen Biologics' aura was dimming day by day, and the data collation and statistical analysis of domestic phase III clinical trials of new crown mRNA vaccines in cooperation with Watson Biologics entered a long end, and the commercialization time window had been lost.

The vaccine development cycle is 8-20 years, and in order to ensure safety, it sometimes takes several years to observe only the toxic side effects. Therefore, the maturity of emerging vaccine companies is later than that of innovative pharmaceutical companies, and the current overall lack of impact is because they are too immature. However, in the context of the epidemic, it was boosted by capital and surpassed the objective growth law.

Abo Creatures waits to fight again in the future.

But Watson Bio can't wait, there is also Plan B, and the broad-spectrum new crown mRNA variant vaccine (S protein chimera) developed in cooperation with Lanque Biotechnology has entered phase III clinical trials.

What is worth learning from vaccine Biotech is the CSPC Pharmaceutical Group, a traditional pharmaceutical company that crosses borders to develop mRNA vaccines with the efficiency of generic drugs, and at the same time does its own upstream supply chain. The upstream key excipients of mRNA have been laid out. The biggest cost comes from hats, which have been independently produced. Other high-cost raw materials such as modified uridine and liposomes can now be synthesized internally, and the cost of vaccines is lower than that of the inactivated route and the recombinant protein route.

CSPC is also developing a general tumor vaccine, with accurate market slots and a layout for a wider range of people, the first is HPV tumor vaccine, followed by tumor vaccines for EGFR mutations in non-small cell lung cancer and HER-2 mutations in breast cancer. In fact, personalized therapy is not suitable for China, because individual ability to pay and commercial medical insurance cannot match sky-high prices.

Some investors have asked Watson Biologics: Why is the company obsessed with the backward mRNA route, can't it make advanced inactivated vaccines? Aren't listed companies for profit? Why not learn from Sinovac?

Behind the ridicule is innovation anxiety.

On August 31 this year, the FDA approved the emergency use authorization (EUAs) applications for Moderna and Pfizer/BioNTech's bivalent new crown mRNA vaccines against the Omicron variant BA.4/BA.5, which took only 63 days from development to approval.

Moderna's CEO used an analogy: Many people buy a new iPhone every September and get new apps installed in it. Similarly, in the future, with a single injection, you will be vaccinated against the new coronavirus, influenza virus and respiratory syncytial virus.

This means that with the blessing of mRNA technology, the vaccine iteration speed is comparable to that of smartphones, and we will have more effort to catch up.

The National Health Commission today requested that the vaccination rate of people over 80 years old be accelerated. This is to accurately cover high-risk groups and reduce the risk of severe illness, critical illness and death in the elderly after being infected with the new coronavirus.

However, the new round of large-scale vaccination (the fourth dose) has not yet been fully launched, and it is still waiting for the truly effective domestic new crown second-generation or multivalent vaccine to be approved for marketing.

There are many vaccines under development in China, specifically for BA.4/BA.5 variants are still relatively scarce, Abogen Biotech against Omicron variant BA.4/5 mRNA vaccine has just entered the clinical stage, Shenzhou cell SCTV01E9 (recombinant tetravalent vaccine) is undergoing phase 3 clinical trial, compared to Pfizer mRNA vaccine, for BA.1 and BA.5 variants, the quadrivalent seedling has reached the preset endpoint of efficacy.

With the help of accurate and effective domestic vaccines, epidemic control can go further, inactivation, recombination, mRNA, who will take the lead in shouldering this national task? Will it take a long time for domestic mRNA vaccines to break the shell and be born?

Vaccines are a microcosm, domestic biomedical technology is still relatively backward, is catching up, breaking through the neck field, the urgency of encouraging innovation is far greater than controlling costs.

In the face of backwardness, it is not appropriate to pause or lie flat, and we should concentrate on economic construction and scientific and technological progress.