The four vaccine giants return to their peak

For a long time, the global vaccine market has been dominated by four giants: Pfizer, Merck, GSK, and Sanofi. This pattern was once disrupted by the sudden outbreak of the COVID-19 pandemic. During this black swan event, new players had the opportunity to compete on the same starting line as the four giants. Looking back, the four giants did not demonstrate their traditional advantages in this competition, with only Pfizer being able to say it had the foresight to collaborate with BioNTech, achieving a historic milestone of over $100 billion in total revenue in 2022. In contrast, the performance of the other three was rather disappointing. Another mRNA vaccine company, Moderna, also emerged strongly, not falling behind in direct competition with Pfizer. Other traditional pharmaceutical companies, including Johnson & Johnson and AstraZeneca, also managed to capture a portion of the market. For a time, the vaccine market underwent significant changes, seemingly ushering in a moment of transformation. However, as the COVID-19 pandemic subsided and entered a phase of normalized control, most companies quickly retreated from the non-core area of vaccines. Even BioNTech, which had earned a substantial amount of money from the COVID-19 vaccine over the years, shifted its focus to acquiring oncology drug projects, expecting to receive its first oncology drug approval in 2026. In contrast, the vaccine business saw a dramatic decline in annual revenue to €2.751 billion (approximately $3 billion), which is quite lamentable. Meanwhile, Moderna, which had also profited immensely, chose to focus solely on vaccines. Unfortunately, even with the launch of its second mRNA vaccine, the RSV vaccination policy from the ACIP under the CDC severely suppressed market potential. The combined revenue from the COVID-19 vaccine Spikevax and the RSV vaccine mRESVIA in 2024 was $3.109 billion, a year-on-year decrease of 53%, with mRESVIA, which went on sale in the third quarter of 2024, recording only $25 million in revenue for the entire year. In 2024, Moderna and BioNTech were almost on par in terms of revenue, but the capital market favored BioNTech, which shifted its focus to "IO+ADC," leading to its market value surpassing that of Moderna. Clearly, investors are not optimistic about Moderna's efforts to break into the vaccine market dominated by the four giants; perhaps only after its oncology vaccine in collaboration with Merck is approved and shows impressive results can it return to an upward trajectory. Thus, it seems that shortly after the COVID-19 pandemic, the global vaccine market has returned to its original market rhythm, with the four giants still leading global vaccine research and supply. Pfizer: Continuously consolidating its advantage in pneumonia vaccines, struggling with COVID-19 and RSV responsibilities In Pfizer's vaccine business, the Pneumococcal vaccine series Prevnar Family remains the top product. As the long-standing flagship product of Pfizer's vaccine segment, it recorded revenues of $6.411 billion in 2024, remaining basically flat compared to 2023. Approximately two-thirds of the revenue comes from the pediatric age group, and the company expects to maintain a stable market share by 2030. However, the adult market, which contributes one-third of the revenue, will face intense competition. The Prevnar 20 vaccine, approved in 2021, holds an absolute advantage in the U.S. market, with a market share of an astonishing 87%. However, Pfizer believes that there are limited opportunities for catching up in the market for individuals aged 65 and older in the U.S., but there are still growth opportunities among the 50-64 age group, which encompasses 30 million people. Moreover, as the eligible population expands, the international market is also growing. To continue maintaining its global leadership in the pneumococcal vaccine market, Pfizer has backup plans. The 25-valent polysaccharide conjugate vaccine PF-07872412, which has already received FDA Fast Track designation, is currently in Phase II clinical trials for adults and infants, with plans to initiate pivotal Phase III clinical trials in the second half of 2025. Phase I clinical trials showed that Prevnar 25 improved the response rate for serotype 3 by a factor of four compared to Prevnar 20. Serotype 3 accounts for about 20% of pneumonia infections in individuals aged 65 and older in Europe and the U.S. Clearly, once approved, Prevnar 25 will be more advantageous for Pfizer to capture the market for individuals aged 65 and older. These research results will help Pfizer formulate development strategies for pneumococcal vaccines with more than 30 serotypes. However, Pfizer also needs to remain vigilant against pressure from competitors. In addition to Merck, GSK, and Sanofi mentioned later, the most formidable challenger may come from Vaxcyte in California, USA. This company is developing a 31-valent pneumococcal vaccine suitable for infants and adults aged 50 and older. Vaxcyte plans to initiate a pivotal Phase III non-inferiority clinical trial in mid-2025, with safety, tolerability, and immunogenicity data expected to be released in 2026. Aside from the Prevnar series, the COVID-19 mRNA vaccine Comirnaty, developed in collaboration with BioNTech, has undoubtedly brought enormous wealth to Pfizer over the past four years. Even though Comirnaty is expected to generate only $5.353 billion in revenue in 2024, a year-on-year decrease of 52%, it remains among the top vaccine products, with cumulative revenue exceeding $90 billion, which is enviable to others. It is foreseeable that the revenue from COVID-19 vaccines will continue to decline in the near future. However, Pfizer has not given up easily and will continue to collaborate with BioNTech to develop the COVID-19 and influenza bivalent vaccine PF-07926307. In August 2024, the two parties announced the results of the Phase III clinical trial for the population aged 18-64. This study achieved one of the two primary immunogenicity goals, showing a high response to influenza A and COVID-19, but failed to meet the goal for influenza B. In another Phase II clinical trial, Pfizer's second-generation trivalent influenza mRNA vaccine demonstrated strong immunogenicity against all strains, with no safety issues compared to the standard influenza vaccine. Originally, Pfizer expected the RSV vaccine Abrysvo to be approved in May 2023, which could offset the impact of declining COVID-19 vaccine revenue. In its first year on the market, Abrysvo showed impressive revenue of $890 million, competing fiercely with its direct competitor Arexvy (GSK). However, by 2024, both Abrysvo and Arexvy faced a significant setback. The ACIP under the CDC in the United States recommended that the vaccination population be strictly limited to those aged 70 and above, leading to a substantial contraction in the RSV vaccine market size, resulting in Abrysvo generating only $755 million in 2024, a year-on-year decrease of 15%. Fortunately, the increase in market share among adults, coupled with strong demand from pregnant women, alleviated the downward trend of Abrysvo. The characteristic of Abrysvo being suitable for pregnant women is not shared by its two competitors Arexvy and mRESVIA. Overall, Abrysvo's competitive position in the U.S. market has further strengthened, and revenue growth outside the U.S. has been robust, especially with the expectation that the EU will approve its use for the 18-59 age group in 2025, which is also expected to further boost its sales. In its 2024 performance report, Pfizer specifically listed four vaccine products in terms of sales revenue. In addition to the pneumococcal, COVID-19, and RSV vaccines, there is the tick-borne encephalitis vaccine FSME-IMMUNE/TicoVac, which contributed $280 million in revenue in 2024, a year-on-year increase of 5%. In August 2021, the FDA approved TicoVac for the prevention of tick-borne encephalitis (TBE) in individuals aged 1 year and older, making it the first FDA-approved TBE vaccine. TBE is a viral infection of the brain and spinal cord that can be transmitted to humans through bites from infected ticks. One-third of TBE patients may experience long-term effects lasting months or years, including cognitive changes, muscle weakness, or permanent paralysis, and in rare cases (0.5%-2%), it can lead to death. Pfizer's TBE vaccine is marketed in Europe under the names FSME-IMMUNE and TicoVac, and in the United States under the name TicoVac. As for the pentavalent meningococcal vaccine PENBRAYA, Pfizer did not mention it in its annual report In addition, a new vaccine product expected to advance to BLA in a short time is PF-07831694. This is a subunit protein vaccine for the prevention of Clostridium difficile infection. Based on preliminary research, Pfizer has improved the formulation and plans to initiate Phase III pivotal clinical trials in the second half of 2025. Merck: HPV vaccine growth hindered; betting on 21-valent pneumonia and RSV monoclonal antibodies, challenging Pfizer and Sanofi respectively. Merck's flagship vaccine product is undoubtedly the HPV vaccine Gardasil. However, compared to a 29% surge in 2023 to USD 8.886 billion, the Gardasil series is expected to generate USD 8.583 billion in revenue in 2024, a year-on-year decrease of 3%, primarily due to declining demand in the Chinese market. As a result, Merck has decided to suspend shipments to China until mid-2025, depending on the situation, hoping to quickly deplete inventory during this period, especially since Gardasil's quadrivalent version was approved for males aged 9-26 in China in January 2025. Domestic HPV vaccines are set to be launched one after another, and before and after this significant impact arrives, Gardasil, as the only HPV vaccine currently suitable for males, may drive a new wave of vaccination enthusiasm. Considering the uncertainty of the recovery time for the Chinese economy, Merck has withdrawn its previously set target of USD 11 billion for Gardasil. However, growth expectations for markets outside of China remain unchanged, with strong growth expected to continue over the next three years. PROQUAD/M-M-R II/VARIVAX (measles/mumps/rubella/varicella combination live vaccine) is expected to generate a total revenue of USD 2.485 billion in 2024, a year-on-year increase of 5%. The five-valent rotavirus live attenuated vaccine RotaTeq contributed USD 711 million in revenue, a year-on-year decrease of 8%. Although Pfizer dominates the pneumonia vaccine market, Merck's three different valency pneumococcal vaccines can also capture a portion of the market share. VAXNEUVANCE (15-valent) is expected to generate USD 808 million in revenue in 2024 (+22%), while PNEUMOVAX 23 (Pneumovax) continues to decline to USD 263 million. The 21-valent CAPVAXIVE was approved by the FDA in June 2024 and received ACIP recommendation, generating USD 50 million in revenue, primarily from retail pharmacy channels. CAPVAXIVE recently also received CHMP recommendation and is expected to be approved in the second quarter of this year. It is anticipated that CAPVAXIVE will engage in direct competition with Pfizer's Prevnar 20. In addition to challenging Pfizer's dominance in the pneumonia vaccine field, Merck also faces tough competition from Sanofi. Merck's long-acting RSV monoclonal antibody Clesrovimab (MK-1654) can serve as a passive immunization method to protect infants from RSV infection during their first RSV season In a pivotal Phase IIb/III clinical trial (CLEVER), a single dose of Clesrovimab significantly reduced RSV-related medical visits requiring at least one lower respiratory infection (LRI) indicator, with an effect that improved by 60% compared to the placebo group in the first five months post-administration. Additionally, Clesrovimab reduced RSV-related hospitalization rates and RSV-related LRI hospitalization rates by 84% and 91%, respectively, within five months. In December 2024, the FDA accepted the marketing application for Clesrovimab, with a PDUFA date of June 10, 2025. Once approved, this drug will become a direct competitor to Sanofi's RSV neutralizing antibody Beyfortus. GSK: Setbacks for shingles and RSV vaccines, meningitis vaccine becomes a hope The full-year revenue of £9.138 billion (approximately $11.697 billion, -7%) is GSK's performance in the vaccine business for 2024. Pfizer and Merck's vaccine segments particularly rely on single products, and GSK is no exception. The largest single product is the shingles vaccine Shingrix, a recombinant subunit adjuvanted vaccine that uses varicella-zoster virus glycoprotein E and the proprietary adjuvant system AS01B to generate a strong and lasting immune response. The vaccine is administered in two doses via intramuscular injection, with the second dose given 2-6 months after the first. Shingrix contributed £3.364 billion in revenue in 2024, a decrease of 2% year-on-year. In the United States, after years of relentless efforts, the cumulative vaccination rate of Shingrix has now reached 40%, an increase of five percentage points compared to 12 months ago, and prices have also risen. However, despite this, Shingrix's annual sales still declined by 18%, due to slow market penetration among hard-to-reach unvaccinated populations, which seems to have hit a ceiling. Additionally, new Medicare rules in the U.S. have changed the reimbursement process for pharmacies, affecting GSK's long-term advantage in retail pharmacy. Clearly, Shingrix is now primarily relying on markets outside the U.S. to maintain growth. Overall, markets outside the U.S. contributed 56% of sales in 2024 (up from only 45% in 2023), with an average vaccination rate of around 7% concentrated in 10 markets. The European market overall continues to grow, with only Germany experiencing a decline in demand. Shingrix has also achieved significant growth in international markets, thanks to a national vaccination program in Australia and supply to partners in the Chinese market. However, GSK is concerned that the supply of Shingrix to China fell in the fourth quarter of 2024, indicating a decline in sales in the Chinese market GSK's other advantageous product is the meningitis vaccine series, with total revenue of £1.437 billion, a year-on-year increase of 14%. The B group meningitis vaccine Bexsero has surpassed £1 billion in annual sales for the first time, thanks to multiple factors including favorable pricing combinations, procurement by the U.S. CDC, vaccination policy recommendations in Germany, and its launch in Vietnam. However, sales of the quadrivalent meningitis vaccine Menveo (ACWY) have declined, primarily due to inventory replenishment by the U.S. CDC in the fourth quarter of 2023. Fortunately, on February 15, 2025, GSK announced that the pentavalent meningococcal polysaccharide conjugate vaccine Penmenvy (MenABCWY) received FDA approval. The world's first RSV vaccine Arexvy has been approved in 59 countries globally, including 17 countries that recommend vaccination for the elderly, including the U.S., and has established a reimbursement system. Affected by the U.S. CDC vaccination policy limiting to seniors aged 75 and above, Arexvy's revenue in 2024 decreased significantly by 52% year-on-year, totaling only £590 million. In 2024, channels are clearing out the stockpiles that began when it was launched in 2023. At the retail level, Arexvy remains the market leader, which is also the preferred vaccination channel for most consumers. Since its market launch in the third quarter of 2023, over 10 million seniors aged 60 and above in the U.S. have been vaccinated. Outside the U.S. market, there has been generally positive market feedback, including vaccination policy recommendations in Germany, shipments beginning after Saudi Arabia's first successful bid, and inventory building in Australia and Brazil; however, perhaps influenced by U.S. policies, demand in Canada also declined in the fourth quarter. The flu vaccine Fluarix/FluLaval faces competitive pressure and declining demand in the U.S. market, leading to a revenue of £408 million in 2024, a year-on-year decrease of 19%. However, after implementing favorable channel pricing combinations, Fluarix/FluLaval returned to growth in the fourth quarter. In addition, other older products from GSK contributed a total of £3.339 billion. In the DTPa series, Boostrix was previously approved by the FDA for the prevention of tetanus, diphtheria, and pertussis in children aged 10 and older, and the latest approval makes it the first vaccine in the U.S. to help protect infants under two months from pertussis, promoting further growth in the U.S. and European markets. In 2024, Boostrix generated revenue of £681 million, a year-on-year increase of 11%. The combination vaccine Infanrix (diphtheria, tetanus toxoid, and acellular pertussis) and the pentavalent vaccine Pediarix (diphtheria, tetanus toxoid, acellular pertussis, recombinant hepatitis B, and inactivated poliovirus) generated revenue of £512 million in 2024, a year-on-year decrease of 8%, due to the U.S. CDC's concentrated procurement for inventory replenishment in 2023. For the same reason, Rotarix (oral rotavirus vaccine) also saw a year-on-year decrease of 4%, with revenue of £587 million Sales of hepatitis vaccines have generally increased across major markets, with a year-on-year growth rate of 13%, achieving revenue of £692 million. The measles/mumps/rubella/chickenpox live attenuated vaccine (MMR/V) Priorix/Priorix Tetra/Varilrix has performed well in both international and U.S. markets, contributing £323 million in 2024, a significant increase of 22%. However, GSK's proud adjuvant platform did not achieve any gains in 2024. Sanofi: Main product revenue is balanced; RSV monoclonal antibody takes on Merck, pneumonia vaccine challenges Pfizer Unlike the other three companies that rely heavily on single products, Sanofi's vaccine segment has a more balanced revenue from its main products. In 2024, revenue reached €8.299 billion, a year-on-year increase of 13.5%, primarily driven by the outstanding performance of the RSV monoclonal antibody Beyfortus (€1.686 billion, +214.4%), particularly with significant contributions from the German and U.S. markets. With capacity expansion approved for the second half of 2024, Beyfortus is expected to continue to ramp up in 2025. Traditional flagship products Polio/Pertussis/Hib (PPH) pentavalent vaccine and booster (mainly Pantaxin in the Chinese market) contributed €2.741 billion in revenue in 2024, showing slight growth (+1.2%); another traditional flagship product, the influenza vaccine, saw a significant year-on-year decline of 36.8% in the fourth quarter of 2024, due to shipments being concentrated in the third quarter of 2024, earlier than in 2023. Overall, the annual sales of the influenza vaccine were €2.555 billion, showing a slight decline (-1.3%), which was also negatively impacted by a recall event in the Chinese market in August 2024. Revenue from other vaccines, such as meningitis, was €1.316 billion, a year-on-year increase of 5.4%. Although affected by the unfavorable procurement model of the U.S. CDC, the meningococcal conjugate vaccine MenQuadfi continued to gain traction in other markets. As previously mentioned, Pfizer and Merck have performed well in the pneumococcal vaccine market, and Sanofi is also entering the arena. The SP0202 vaccine, developed in collaboration with SK Bioscience, has already initiated Phase III clinical trials, with the first dose expected to be administered in Australia in December 2024. The plan is to recruit 7,700 participants, including adolescents and infants, across multiple global regions including the U.S., Europe, Australia, Asia, and Latin America. This will be the world's first Phase III clinical trial of a 20-valent or higher pneumococcal conjugate vaccine in infants. The two parties will also further collaborate to develop the next generation of pneumococcal vaccines, incorporating serotypes not included in existing conjugate vaccines Another vaccine product in the late clinical stage is the Escherichia coli sepsis 9-valent conjugate vaccine (ExPEC) SP0282, introduced from Johnson & Johnson, which is scheduled to read out Phase III clinical trial data in 2026. In addition, Sanofi's traditional stronghold in influenza is also a key R&D project for the company, along with the newly emerged coronavirus and the significantly breakthrough RSV virus in recent years, and even the human metapneumovirus (hMPV) discovered in 2001, for which Sanofi is also developing a new generation of products, including combination vaccines. The Battle of the Four Giants in the China-U.S. Market Looking at the product line layout of the four giants, apart from Merck and GSK each exclusively holding the HPV and shingles markets, and the other three companies being significantly behind Pfizer in the competition for COVID-19, other areas are highly concentrated, including pneumococcus, RSV, influenza, meningitis, and the combination vaccine for measles, mumps, rubella, and varicella, which are in fierce competition with each other, marking a vigorous battle among the four giants. The vaccine market has its own unique game rules. Therefore, the four giants not only need to be vigilant against internal and external competitors but also face significant challenges from changes in the market environment, especially in the two major markets of China and the U.S. In China, the four giants seem to have reached some tacit understanding, maintaining a strong sense of boundaries and not directly competing with each other. Currently, the vaccines sold in China are all their flagship products, including Pfizer's pneumococcal vaccine, Merck's HPV vaccine, GSK's shingles vaccine, and Sanofi's influenza vaccine, polio pentavalent vaccine, and RSV monoclonal antibody. The competition faced by the four giants in China comes more from local vaccine companies and how to adapt to China's game rules. However, apart from Sanofi, which still retains its own commercial team and factory, the other three have chosen to entrust their vaccine products to agents. This is related to the uniqueness of China's vaccine regulation and commercialization, as well as the fierce competition in the industry. In the U.S., although the market space is larger, the challenges faced are also the greatest. After Trump's return to the White House, the new leadership of the U.S. government not only includes staunch anti-vaccine individuals but is also cutting staff from health regulatory agencies, including the FDA and CDC. Looking back at Trump's handling of the COVID-19 pandemic during his first term raises concerns among the four giants. How to respond to these changes is worth keeping an eye on. However, what remains unchanged is that, with the industry foundation accumulated over a long time, the four giants still firmly hold the global vaccine market