By Kate Goodwin

Pictured: A researcher at work in a Novavax laboratory/Novavax, Patrick Siebert
Combination vaccines are nothing new for the healthcare industry. Childhood vaccines, as well as a single shot for tetanus, diphtheria and pertussis for adults, have long been combined for ease of administration and increased compliance rates.
Now, as vaccines for COVID-19 and, for older people, RSV and pneumococcal disease join the annual flu shot as routine care recommendations for adults, healthcare professionals are increasingly concerned over getting the word out, vaccine fatigue and logistical hurdles. Biopharma companies are betting there will be a market for vaccines that combine protection against two or more diseases in a single jab.
Benefit to the Population
“The data are pretty unequivocal that when there are combo vaccines available, people generally prefer [them],” said Andrea C. Love, an immunologist and microbiologist and founder of the Unbiased Science Podcast.
Love pointed out the convenience of the combination vaccines is a big positive for patients. She and others in the industry anticipate that a more streamlined process will increase vaccination compliance. Additionally, timely vaccination reduces the burden of illness for recipients.
Despite its benefits, vaccinations for COVID-19 have been on the decline. In October, Pfizer cut its revenue outlook for 2023 by $2 billion due to lower demand for Comirnaty. The CDC reported that as of October 14, only 7% of adults and 2% of children had obtained the latest bivalent booster shot against COVID-19.
And just under half of adults received a vaccine against flu in the most recent year for which the agency has released data. Uptake has fallen, particularly in the 18 to 49 age group. Yet the flu remains a deadly illness: The CDC reported 290,000 hospitalizations and 19,000 deaths from influenza in the 2022-2023 flu season as pediatric hospitalizations and mortality rates reached highs that haven’t been seen in years.
Respiratory syncytial virus (RSV) is the newest addition to the vaccine lineup. The virus leads to 100–300 deaths in children under 5 and 6,000–10,000 deaths in adults over 65 each year. Two vaccines have now been approved to prevent RSV in people over 60, with other companies in late-stage testing. Pfizer’s Abrysvo is also indicated for use during pregnancy to protect infants from birth to 6 months of age. Analysts estimate the market will exceed $9 billion by 2029.
Combo Vaccines in the Pipeline
In the face of dwindling vaccination rates, multiple biopharma companies are now developing shots that combine protection against two or even three respiratory illnesses.
Moderna has a handful of combos in the pipeline for flu plus COVID-19; flu, COVID-19 and RSV; and flu plus RSV. Phase I/II data from its quadrivalent influenza and COVID-19 vaccine were reported in early October, showing strong immunogenicity with an acceptable safety profile compared to standalone vaccines. The company is now moving into Phase III. Likewise, Pfizer and BioNTech announced positive topline data for an mRNA-based vaccine targeting influenza A, B and COVID-19, and it will be headed into Phase III.
Novavax has a vaccine for COVID-19 already on the market and a seasonal influenza shot in Phase III. The company is now working on combining the two into a single shot, hoping that decreasing the number of medical contact visits required will increase the number of people willing to get vaccinated, said Novavax President of R&D Filip Dubovsky.
Novavax’s platform leaves the door open to potentially add in protection against other viruses as well, such as RSV, for which it already has a candidate in the pipeline.
“It’s our understanding from discussing both with consumers as well as healthcare providers that there’s a strong demand for a combination product, and it makes all the sense in the world,” Dobovsky said.
The path for Novavax has been much quicker than traditional R&D because components of the vaccines have already been in use, allowing the company to move rapidly into human testing.
As these companies look to combine their already-approved or nearing-approval products, smaller player Icosavax came straight out of the gate with a combo vaccine candidate for RSV and human metapneumovirus (hMPV), a cousin to RSV. The candidate is in Phase II and has already received Fast Track Designation from the FDA.
“We’ve been able to go right to a combination approach,” Icosavax CEO Adam Simpson told BioSpace, pointing out that the FDA seems open to this based on the designation.
The company put RSV and hMPV together because the viruses don’t change every year. Simpson said Icosavax is hoping for a longer-acting vaccine with the right technology, foregoing the need for annual dosing.
Andy Hsieh, a William Blair analyst who covers Icosavax, noted that while the pediatric population has been rife with combination vaccines, the elderly population “has not been mature” in this market. “I think it makes very logical sense that the same benefit that was conferred to the pediatric population should also be extended for the elderly population,” Hsieh said.
The market for RSV protection might take some time to build, he told BioSpace, as it’s not as commonly known as flu or COVID-19. At this point, the Advisory Committee on Immunization Practices (ACIP) recommendations for RSV vaccination are not as strong as those for COVID-19. Rather than recommending vaccination for everyone who is eligible, ACIP recommends that it be a shared decision for those 60 and older to make with their healthcare providers.
Pfizer CEO Albert Bourla told investors on a recent call that he believes the combo shots will “unlock a significant potential by improving the vaccination rates.” Whether these combination shots will really move the needle on public vaccination rates remains to be seen.