Pneumonia Vaccine "Midfield Battle": Local Enterprises Break Monopoly And Multinational Giants Complete Iteration

With the approval of new products from domestic and foreign enterprises, the market competition of pneumonia vaccine has entered a new stage.

On July 16, local time, MSD announced that the US FDA approved the launch of its pneumococcal 15 valent conjugate vaccine vaxneuvance. In addition, Pfizer has completed the iteration of its flagship pneumonia vaccine product pcv13. On June 8, the FDA approved the launch of Pfizer's 20 valent pneumonia vaccine.

Meanwhile, on July 14, China's local vaccine enterprise Kangtai bio revealed that the world's first "dual carrier 13 valent pneumococcal polysaccharide conjugate vaccine" independently developed and produced by China will be approved for listing. The vaccine is independently developed by Beijing minhai Biotechnology Co., Ltd., a wholly-owned subsidiary of Shenzhen Kangtai Biological Products Co., Ltd. It combines two carrier proteins with pneumococcal capsular polysaccharide, and is suitable for 6-5-week-old patients.

In 2020, the total revenue of the top 10 vaccine products in the world is as high as 23.89 billion US dollars, among which the sales of 13 price pneumococcal polysaccharide conjugate vaccine, HPV vaccine, influenza vaccine, diphtheria tetanus series combined vaccine and recombinant herpes zoster vaccine are far ahead.

Among them, Pfizer's 13 valent pneumococcal conjugate vaccine is well sold all over the world. Before the new crown vaccine came out, it was the "king of vaccines". In 2018, the global sales volume was close to US $6 billion, far exceeding the second place in vaccine sales of 9-price HPV vaccine (US $3.15 billion).

At present, pneumococcal vaccines approved for marketing worldwide include pneumococcal conjugate vaccine and pneumococcal polysaccharide vaccine, while only pneumococcal conjugate vaccine can be given to infants under 2 years old. Compared with polysaccharide vaccine, the combined vaccine is more difficult to prepare.

In recent ten years, 13 valent pneumonia vaccines in China's market are mainly supplied by foreign enterprises. With the breakthrough of domestic pneumonia vaccine, the situation of insufficient production and high price for a long time is being solved after the acceleration of domestic vaccine research and development process.

Rapid rise of domestic vaccine products

At present, the domestic listed pneumonia vaccine products mainly include 7-valent pneumococcal conjugate vaccine, 13 valent pneumococcal conjugate vaccine and 23 valent pneumococcal polysaccharide vaccine (the 7-valent pneumonia vaccine was withdrawn from the domestic market in 2014). Among them, 23 valent pneumococcal polysaccharide vaccines use 23 widely prevalent and invasive serotypes of pneumococci (including serotypes 1, 2, 3, 4, 5, 6b, 7F, 8, 9N, 9V, 10a, etc.) The antigens of 23 serotypes of pneumococcal capsular polysaccharide were cultured, inactivated and purified, and then mixed and packed separately.

In 2005, the preclinical study of bivalent 13 valent pneumococcal vaccine was started. In 2019, the drug production approval registration application was accepted by the State Drug Administration.

More than 2000 researchers were recruited in the phase III clinical trial of this vaccine and the non inferiority test of the original product developed by American enterprises. The main clinical endpoint was the positive conversion rate and geometric average concentration of specific IgG antibody of 13 serotypes.

The results showed that the IgG of all age groups after whole course immunization was higher than 0.35 μ The percentage of subjects with g / ml was close to 100%. In the experimental results of the 2-6-month-old group, the positive rate of IgG antibody of 13 serotypes in the experimental group was not inferior to that of the original products of American enterprises after the whole course of basic immunization (3 doses) or enhanced immunization (the fourth dose).

In fact, since the world's second and China's first 13 valent pneumococcal polysaccharide conjugate vaccine Watson bio was approved for listing in December 2019, the war of import substitution of domestic 13 valent pneumococcal vaccine has started.

In 2008, China introduced Wyeth's 7-valent pneumococcal vaccine, which was withdrawn from the domestic market due to the expiration of its import license in 2015. In 2019, Pfizer is the only enterprise approved to issue 13 valent pneumonia conjugate vaccine in China.

Since the launch of Pfizer's 13 price pneumonia vaccine in 2016, it has been approved and signed in large quantities year by year, but the supply still falls short of demand. 715000 pieces were issued in 2017, 3.85 million pieces (+ 438.5%) in 2018, and 4.75 million pieces (+ 23.4%) in 2019. A total of 9.315 million pieces were approved and issued in three years.

According to the standard vaccination program of 4 injections per person, Pfizer 13 valent pneumonia conjugate vaccine has only benefited about 2.3 million infants and young children under the age of 2 years since it was launched in China. However, in recent years, the annual birth scale of infants in China is about 15 million (15.23 million in 2018), and the supply side capacity is limited, and the market continues to be seriously in short supply.

On December 31, 2019, Watson biological 13 valent pneumonia conjugate vaccine was approved by the State Food and drug administration, which played a role in alleviating the supply shortage.

It is worth mentioning that at present, the domestic R & D is still dominated by me too, and the original new vaccine needs more clinical trial design innovation: the 13 valent pneumonia vaccine has been listed overseas for many years, and the corresponding relationship between antibody and protection rate is clear. Therefore, at this stage, domestic vaccine research and development is often accelerated by skipping phase II clinical practice. Vaccines with new indications and antigens need to design vaccination procedures, select clinical endpoints, and explore mature alternative endpoints, which often require more clinical innovation.

The research and development cycle of the vaccine is 10 years. Judging from the domestic 13 valent pneumonia research and development experience, the pre clinical time is the longest: the domestic multivalent pneumonia vaccine basically takes more than 5 years from project approval to clinical use.

In the super long dimensional R & D cycle, the importance of time cost is far greater than the material cost, so it is more important to predict the epidemic changes and carry out technical reserve as soon as possible.

Now, the 13 price pneumonia vaccine has begun to contribute revenue to Watson biological, adding to its international sales.

According to the announcement, in the first quarter of 2021, 1.643 million bottles of 13 price pneumonia vaccine were approved and issued by its subsidiary, accounting for 36.8% of the total amount issued in 2020. At the same time, the subsidiary reached an exclusive agreement with marocvax of Morocco. Marocvax guarantees to obtain marketing permission within 18 months after receiving the complete product registration file. In 2021, about 2 million doses of the vaccine will be sold in Morocco. After the technology transfer, marocvax will continue to purchase vaccine stock equivalent to at least 2 million doses.

New vaccines from multinational giants are coming on the market

At the time of breakthrough of domestic pneumonia vaccine, multinational vaccine giants are also busy with iterative upgrading of their pneumonia vaccine products.

On July 16, local time, MSD announced that the U.S. Food and Drug Administration approved the launch of its pneumococcal 15 valent conjugate vaccine vaxneuvance to prevent invasive diseases caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6a, 6b, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F in adults over the age of 18. Vaxneuvance has been granted priority qualification by FDA. In January this year, MSD announced that the FDA had accepted its application for a biological product license (BLA) for the development of a 15 valent Streptococcus pneumoniae vaccine vaxneuvance to prevent invasive pneumococcal disease in adults over the age of 18. The European Drug Administration (EMA) is also reviewing vaxneuvance's regulatory application.

The data showed that mosartan vaxneuvance could cover 13 serotypes of Pfizer's top brand pneumonia vaccine pcv13, and had stronger immune response to three of them. In addition, 22F and 33F, which are not covered by pcv13, are also covered.

It is worth mentioning that Pfizer has also completed the iteration of pcv13. On June 8, a month ago, Pfizer announced that the US FDA had approved prevnar 20 (pneumococcal 20 valent conjugate vaccine, 20vpnc) to prevent invasive diseases and pneumonia caused by the serotype of Streptococcus pneumoniae in the vaccine for adults aged 18 and above. Pfizer said it was the first approval of a conjugate vaccine against 20 pneumococcal serotypes that cause most invasive diseases and pneumonia, including seven serotypes that cause 40% of pneumococcal disease cases and deaths in the United States. Compared with pcv13, the 20 valent vaccine covers 7 serotypes: 8, 10a, 11a, 12F, 15b, 22F and 33F, that is to say, more serotypes 8, 10a, 11a, 12F and 15b are covered by the 20 valent vaccine.

Fierce competition in the domestic market in the future

In 2020, in order to prevent and control the new epidemic situation and promote the joint vaccination of pneumonia vaccine and influenza vaccine, the batch issuance of pneumonia vaccine reached a new high in recent years. A total of 27.17 million doses of full caliber pneumonia vaccine were approved and issued in the whole year, with a year-on-year increase of 91.0%; Among them, 10.78 million doses of 13 valent pneumococcal conjugate vaccine were issued, an increase of 126.7%, and 16.39 million doses of 23 valent pneumococcal polysaccharide vaccine were issued, with a year-on-year increase of 73%, both reaching a record high. Among the full caliber pneumonia vaccines, 39.6% of them were signed with 13 valent pneumococcal conjugate vaccine and 60.3% were 23 valent pneumococcal polysaccharide vaccine.

From the perspective of full caliber pneumonia vaccine, Watson biological pneumonia vaccine product line is relatively complete, covering 13 valent pneumococcal conjugate vaccine and 23 valent pneumococcal polysaccharide vaccine, and its batch issuance and market share are leading.

At present, only Pfizer and Watson biological have issued 13 valent pneumococcal conjugate vaccine products. By the end of 2019, the 13 valent pneumococcal conjugate vaccine of Watson biology was approved to be on the market, filling the perennial market supply gap. In the future, with the approval of Kangtai's minhai 13 valent pneumococcal conjugate vaccine and Zhifei Lvzhu 15 valent pneumonia conjugate vaccine, the market supply will be further increased and the market competition will be enhanced.

According to the first securities research report, a total of 10.78 million doses of 13 valent pneumococcal conjugate vaccine were approved and issued in 2020, of which 6.42 million doses were issued by Pfizer, accounting for 59.6% of the market, and 4.36 million doses were issued by Watson biological, accounting for 40.4% of the total.

In terms of 23 valent pneumococcal polysaccharide vaccine, 16.39 million doses of pneumococcal polysaccharide vaccine will be approved and issued in 2020, with 4 enterprises in total. The market pattern is dominated by domestic enterprises. Chengdu Institute of traditional Chinese medicine had 7.08 million doses, accounting for 43.2% of the total; Watson biological batch issued 5.11 million doses, accounting for 31.2% of the market, ranking second; 3.71 million doses were approved and issued, accounting for 22.7% of the total; There were only 478000 doses of moshadong, accounting for 2.9% of the market.

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