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text | Same as freehand, author丨Buqi, editor丨Yu Jing
Since the disclosure of positive phase II data of VLA15 in children (VLA15-221) two months ago, Pfizer and Valneva decided to further deepen their cooperation.
Earlier this week (June 20), Pfizer announced that it would acquire 8.1% of the French vaccine company Valneva at a price of 9.49 euros per share, for a total consideration of 90.5 million euros (approximately US$95.24 million). The transaction will be completed by June 22, and Valneva plans to use the proceeds to support the Phase III clinical development of VLA15.
Pfizer and Valneva also updated the cooperation agreement signed in April 2020.
and the two previously agreed that Valneva would bear 30% of the development costs of VLA15, and after this modification, this proportion will increase to 40%. At the same time, the tiered royalties that Pfizer will pay Valneva will also change from the original 19% to 14% to 22%. If the product is ultimately approved, Pfizer will also pay Valneva up to $100 million in milestone payments based on cumulative sales.
Other development and early commercialization milestones remain unchanged, including the $25 million Pfizer will pay Valneva when VLA15 initiates Phase III clinical trials. At present, Valneva is expected to receive this income this year.
01 The only Lyme disease vaccine under research may enter Phase III clinical trials in 2022Q3
As the only Lyme disease vaccine candidate in clinical development in the world, VLA15 also has high hopes from the industry. Lyme disease is a natural focal disease caused by Borrelia burgdorferi and is mainly spread by ticks. Lyme disease can lead to more serious complications that affect the joints (arthritis), heart (myocarditis) or nervous system , and the preventive measures available so far are only "guidelines" for avoiding tick bites.
Although the industry does not know the true incidence of Lyme disease, it is conservatively estimated that nearly 500,000 people are diagnosed with Lyme disease in the United States every year, and this figure is more than 200,000 in Europe. As the disease spreads, the size of the population behind it is likely to grow.
In 1998, a Lyme disease vaccine, LYMErix, was approved for marketing, but was hastily withdrawn due to safety and other issues. Lawsuits at the time claimed the vaccine caused severe arthritis in recipients and other symptoms of Lyme disease that the vaccine was supposed to prevent. On the other hand, the efficacy of LYMErix seems to be poor. It only reached 80% of immunity after three injections, and subsequent supplementary doses are still needed.
But LYMErix is not without its merits. It at least points to one of the breakthrough points, Borrelia burgdorferi surface protein a (OspA). Subsequently, researchers began to develop a new generation of vaccines around OspA, lipid immunogens, and live mutants in an attempt to disrupt the bacterial infection process.
VLA15, chosen by Pfizer, is a multivalent vaccine against OspA, covering the six OspA serotypes (ST1-ST6) popular in North America and Europe. In fact, VLA15 is not only favored by Pfizer. Looking at VLA15's "selling oneself" experience, it can be said that it has been full of twists and turns.
In 2007, Intercell, a biotechnology company from Austria , teamed up with Novartis to develop infectious disease vaccines. But then in 2013, Intercell merged with French vaccine company Vivalis to form Valneva. On the other side, Novartis divested most of its vaccine business to GSK in 2015, which involved the Lyme disease vaccine project. In 2019, the original "Strategic Alliance Agreement" (SAA) formed by Intercell and Novartis was terminated. Valneva paid a total of 16 million euros to GSK and fully obtained related assets including VLA15.
Interestingly, in the second year after obtaining complete ownership of VLA15, Valneva reached a joint development and commercialization agreement with Pfizer. The total consideration for this cooperation is as high as US$308 million for , including an upfront payment of US$130 million, a development milestone payment of US$35 million, and a sales milestone payment of US$143 million. The reason for the increase in
’s value may be the good performance of VLA15 in the past. In July 2017, VLA15 received the fast track designation of FDA. Looking at it now, the late-stage data of VLA15 proves that Pfizer has a high probability of making a bet.
As part of its collaboration with Pfizer, Valneva is accelerating the development of VLA15 in pediatric populations, launching additional Phase II clinical trials in March 2021.In July 2021, Pfizer and Valneva announced the completion of recruitment for VLA15-221 with a total of 625 participants, ranging in age from 5 to 65 years old. In April 2022, both parties announced positive Phase II data for children. In the
VLA15-221 study, Valneva compared the immunogenicity and safety of after two and three doses of VLA15 in the 5-11 year old, 12-17 year old and 18-65 year old age groups respectively.
Compared with the strong immunogenicity characteristics of Phase II clinical trials in adults (18-65 years old) reported in February 2022, the data shows that in the 5-17 year old group, the immunogenicity level of VLA15 after two or three doses is higher. high. Moreover, the safety and tolerability observed in the 5-17 year old group were similar to those previously reported in adult subjects, and no serious adverse events (SAE) related to the vaccine were observed.
This means that, as with adults, the above data on pediatric subjects will support Valneva in including 5-17 year olds in the Phase III clinical trials of VLA15.
Valneva and Pfizer said that VLA15 will enter Phase III clinical trials in the third quarter of this year. Industry insiders estimate that if clinical development is successfully completed, VLA15’s marketing application is expected to be accepted by the FDA as early as 2025. This is of great significance to Pfizer.
02 In the post-COVID era, can “Buy Buy Buy” defend the name of the giant?
As we all know, the vaccine segment has been Pfizer’s revenue-generating pillar for a long time. Especially after the COVID-19 epidemic, Pfizer has further consolidated its advantages with the mRNA vaccine Comirnaty. In the first quarter of this year alone, Comirnaty's sales reached US$13.2 billion, far exceeding the performance of Moderna's new coronavirus mRNA vaccine Spikevax, which had only US$5.9 billion in revenue. But on the other hand, it is undeniable that there is not much incremental market left in the COVID-19 field.
On June 6, the National Broadcasting Corporation (NBC) reported that the current new crown vaccine is wasted. Citing data released by the US CDC, from December 2020 to May this year, the US wasted a total of approximately 82.1 million doses of COVID-19 vaccines, accounting for more than 11% of the total vaccines distributed by the federal government.
This problem does not only appear in the United States. Recently, European countries such as the United Kingdom, Denmark, and Switzerland have also begun to destroy expired COVID-19 vaccines. Vaccine developers, including Pfizer, have revised their cooperation agreements with the European Commission to allow the postponement of the delivery of the new crown vaccine that was originally scheduled to be delivered.
When the "dividend" disappears, Pfizer is bound to bear the pressure of declining revenue generation. Due to the birth of generic drugs, 2025-2030 will undoubtedly be full of challenges for Pfizer.
Earlier this year, Pfizer CEO Albert Bourla stated at the JP Morgan conference: "If we want, we have the ability to conduct any transaction." As the head of this MNC, he claimed that will increase investment in small and medium-sized enterprises biotechnology companies, and there are no caps on M&A transactions.
This is indeed the case. In March 2021, Pfizer acquired drug development company Arena for US$6.7 billion to supplement the inflammation and immunology business pipeline. In August 2021, Pfizer acquired Canadian drug developer Trillium for US$2.26 billion, acquiring two cancer drugs in early clinical stages. And just last month, this giant spent a huge amount of US$11.6 billion to completely buy out Biohaven, a dark horse in the migraine market.
But if you look at the accumulation, the title of "one of the four vaccine giants" somewhat means that Pfizer is unwilling to give up this track easily. In addition to COVID-19, Pfizer is also developing vaccines for other infectious diseases.
However, this aspect has been somewhat lost recently.
html In March, Pfizer announced that Clostridium difficile vaccine candidate PF-06425090 missed the primary endpoint of preventing infection in a pivotal Phase III trial. Although Pfizer emphasized that it will not give up its research and development work on this vaccine and is evaluating the next step in the research of Clostridium difficile vaccine candidate PF-06425090, this setback has indeed clouded the future of a potential blockbuster project.Pfizer had previously optimistically predicted that PF-06425090 would be launched in 2021 and create peak sales of up to US$300 million. After this phase III clinical failure, some analysts said that even if the vaccine is likely to be approved, its future performance may not be too optimistic and it will be difficult to reach a peak commercial sales of more than 1 billion US dollars.
Clostridium difficile causes about 500,000 infections and 25,000 deaths in the United States every year. Similar to Lyme disease, there is currently a lack of effective vaccines to prevent Clostridium difficile infection. Another failure in this regard is and sanofi , which has stopped the development of related projects.
It is worth noting that Valneva’s other Clostridium difficile vaccine candidate, VLA84, has completed Phase II clinical trials. In view of Pfizer's investment in the vaccine field, it is not ruled out that it will cooperate with Valneva in other indications in the future. has even staged the same drama of cooperation first and merger and acquisition later as in the Biohaven case.
However, regulation may hinder Pfizer's efforts to some extent. Recently, the U.S. Federal Trade Commission (FTC) has expressed concerns about the consolidation of the biopharmaceutical industry and the expansion of market power by existing leading companies through mergers and acquisitions.
Since March 2021, the FTC has been working with international counterparts to revise antitrust reviews of pharmaceutical companies. U.S. antitrust regulators say the current process for reviewing Big Pharma mergers simply isn't working.
FTC experts believe that scale expansion cannot promote innovation in the biopharmaceutical field. Patricia Danzon, an expert in health care economics at the University of Pennsylvania, said that in the past few years, the share of new drugs by large pharmaceutical companies has gradually declined, while small companies have contributed about 70% of new drug entities. Research by
found that merged companies experienced a decline in R&D output, and there were concerns that buyers would stymie innovation by acquiring competitors.
Experts are also worried that the increased bargaining power of big pharmaceutical companies in drug pricing negotiations will disrupt market order. If the merged biopharma company has a "must" or blockbuster product, the company can bundle the star drug with the new product acquired through the acquisition, driving up prices. Many studies have shown that there is a strong relationship between high market concentration and rising drug prices.
As for the final direction of the industry, it remains to be seen. Before that, Pfizer may only be "crossing the river by feeling the stones."
Reference:
- The fourth new coronavirus vaccine in the United States? What did Novavax miss and what will happen in the future? Will the underestimation of the market lead to a huge wave of mergers and acquisitions? The CEOs of Pfizer, Gilead, and AstraZeneca have different opinions; with Yiyi
- ’s first tens-billion-dollar acquisition in 2022, what can Pfizer bring to the migraine market and MNC? ; Tongyiyi
- FTC cracks down on pharmaceutical company mergers and acquisitions, large-scale transactions may face a "chilling" effect; Tongyiyi
- missed the primary endpoint, Pfizer's Clostridium difficile vaccine phase III trial failed; Yiyi Pharmaceutical
- The world's first Lyme disease vaccine, Valneva 1,000 Duowan was bought out from GSK and sold to Pfizer for US$300 million; PharmSnap
- Valneva and Pfizer Enter into an Equity Subscription Agreement and Update Terms of Collaboration Agreement for Lyme Disease Vaccine Candidate VLA15; Pfizer
- Valneva Announces Mutual Agreement with GSK to End Strategic Alliance Agreement; Regains Control of RD; Valneva
- Valneva and Pfizer Report Positive Phase 2 Pediatric Data for Lyme Disease Vaccine Candidate; Pfizer
