Pfizer and BioNTech announced that a phase 3 clinical trial of their combination flu and COVID mRNA vaccine to protect against influenza and COVID-19 found the vaccine failed to meet one of the study’s two main goals. The companies are evaluating the possible next steps for this vaccine.

I know there is a myth that any vaccine invented by the pharmaceutical industry immediately ends up in humans, but that’s not how it happens. The whole point of clinical trials, particularly in phase 3, is to determine if a drug or vaccine is safe and effective in a statistically significant population.

In this case, Pfizer and BioNTech realized that their preliminary analysis of data from the phase 3 trials showed that the combination COVID-flu vaccine did not meet the effectiveness levels necessary to submit it to the FDA.

Let’s review what happened with this new vaccine and discuss the next steps for further development.

Combination flu COVID vaccine clinical trial results

The vaccine candidate combines Pfizer’s quadrivalent modified mRNA-based influenza vaccine candidate, qIRV (22/23), which is currently in Phase 3 clinical development, and Pfizer and BioNTech’s authorized Omicron-adapted bivalent COVID-19 BNT162b2 (Original/Omicron BA.4/BA.5) vaccine.

Phase 3 clinical trial to evaluate the companies’ combined mRNA vaccine candidate against influenza and COVID-19 in healthy individuals 18-64 years of age. The combination candidate consists of Pfizer’s mRNA-based influenza vaccine candidate with the companies’ licensed COVID-19 vaccine. The Phase 3 trial measured two primary immunogenicity objectives (immunogenicity against SARS-CoV-2 as well as immunogenicity against influenza A and B), of which one was met.

According to Pfizer and BioNTech:

• In a Phase 3 trial, Pfizer and BioNTech’s combination vaccine candidate against influenza and COVID-19 met one of its primary immunogenicity objectives.
• The trial did not meet one of its primary immunogenicity objectives of non-inferiority against the influenza B strain despite obtaining higher influenza A responses and comparable COVID-19 responses versus the comparator vaccines.

In other words, the COVID component of the combination vaccine worked against COVID, but the flu component worked against the influenza A strains, but not against the influenza B strain. Influenza A strains are currently more concerning as they include the H3N2 and H1N1 strains that can cause pandemics. Unfortunately, a vaccine that does not provide the immune response against the influenza B strain probably would not be acceptable.

What can the companies do next?

The companies will discuss the results with regulatory agencies such as the FDA and the European Medicines Agency. Together, they would determine what the next steps would be, but a flu vaccine component that was not effective against the influenza B strains would probably require reworking of the vaccine.

Pfizer has a separate phase 2 trial that is evaluating a trivalent influenza mRNA standalone vaccine candidate that has shown immunogenicity against the circulating strains of the flu in individuals 18-64 years of age. They could rework that vaccine with the COVID vaccine to produce a new combination vaccine.

Whatever the case, this will put a serious delay in getting the new combination vaccine out to the public. I would love to get one vaccination for both COVID and the flu, but I guess it will have to wait for a few years.