It has been a bumpy ride for biopharma to develop a vaccine for the potentially deadly respiratory syncytial virus (RSV), since the 1960s. As GSK and Pfizer battled it out earlier this year, with the former’s Arexvy vaccine crowned the first-ever RSV vaccine to hit the market, a mere few weeks before Pfizer received the approval from the U.S. Food and Drug Administration (FDA), AstraZeneca has now joined the vaccine development race with its latest acquisition.
The multinational giant AstraZeneca’s $1.1 billion deal with American clinical-stage company Icosavax, will strengthen its position in the RSV therapeutic research space, as it is also the co-developer of Beyfortus, an antibody designed to protect infants born during the RSV season. Purchasing Icosavax means that it will get its hands on the latter’s RSV vaccine candidate, which is being evaluated in the clinic.
Why is there a need for RSV vaccines?
Vaccine development for preventing RSV has been far from a walk in the park. And, while symptoms are similar to a cold, where patients may develop a fever and chest congestion, the virus can be unpredictable, and thereby life-threatening if untreated in babies, older adults and adults with chronic medical conditions.
In fact, the disease affects around 64 million people and causes 160,000 deaths globally, each year, according to the National Institute of Allergy and Infectious Diseases. Although monoclonal antibodies like Swedish Orphan Biovitrum’s Synagis (palivizumab) are given to children who are at risk of being ill from RSV, the protection doesn’t last long, and has to be administered once a month during RSV season.
And that’s why biopharmas have been rushing to create RSV vaccines lately.
The first attempt at creating an RSV vaccine failed when a formalin-inactivated RSV (FI-RSV) vaccine triggered severe immune reactions, and led to the death of two children in the 1960s. This halted RSV vaccine development for years to come.
Eventually, scientists tried to use different formulations to create a vaccine, but to no avail. Then, big pharma companies decided to take a stab at vaccine-led immunization against the virus, thereby making 2023 a promising year for RSV vaccines.
GSK and Pfizer go head-to-head in the RSV vaccine approval race
This year, GSK’s RSV vaccine became the first vaccine against the deadly virus to hit the market after the FDA’s approval in May. Arexvy is an adjuvanted vaccine that contains a recombinant subunit prefusion RSV F glycoprotein antigen (RSVPreF3) combined with GSK’s proprietary AS01E adjuvant. It works by enhancing antigen-specific cellular immune and neutralizing antibody responses against RSV. The adjuvant helps boost the response by activating the antigen-presenting cells which carry the vaccine-derived antigens.
The FDA has legalized it for people aged 60 and over, after the vaccine expressed an 82.6% overall efficacy in patients in a phase 3 trial. Moreover, it was found to be efficacious in nearly 95% of patients with underlying medical conditions. In another trial to expand the patient population that could benefit from the vaccine, preliminary results showed that primary endpoints were met in a phase 3 trial comprising adults aged 50 to 59.
But it was not just the year of Arexvy. Pfizer was head-to-head with GSK to win an FDA approval for its RSV vaccine ABRYSVO, and it came a close second. ABRYSVO is the first ever maternal vaccine to enter the market to help protect infants at birth until six months of age against RSV. The go-ahead from the drug regulator was following phase 3 trial results in more than 7,000 pregnant people.
The non-adjuvanted vaccine, which is composed of two preF proteins, was found to be 82% effective at preventing RSV-induced illness at 90 days after birth, and 69% effective at 180 days. Furthermore, the vaccine was 68% effective at preventing RSV-related hospitalizations through 90 days after birth, and 57% effective through 180 days.
“Newborns and young infants – whose immune systems are still developing, and are not yet strong enough to defend against infections – may now be protected from RSV from the moment of birth through maternal immunization,” said Eric A.F. Simões, clinical professor in Pediatrics-Infectious Diseases at University of Colorado School of Medicine and Children’s Hospital Colorado in the U.S., in a press release.
Moderna follows behind in RSV vaccine development
Meanwhile, multinational company Moderna, famed for its mRNA therapeutics, is looking to bring its RSV vaccine candidate to the market soon. It submitted an application for regulatory approval as well as a Biologics License Application in July. Its investigational candidate MRNA-1345, consists of a single mRNA sequence encoding for a stabilized prefusion F glycoprotein. The vaccine uses the same lipid nanoparticles (LNPs) as in the pharmaceutical’s COVID-19 vaccines. The F glycoprotein on the surface of the virus helps the virus enter host cells.
In a phase 3 trial that met the primary endpoint, the vaccine demonstrated an 83.7% efficacy in older adults, and was found to be well-tolerated with no safety concerns identified. The trial was a randomized, double-blind, placebo-controlled study of around 37,000 people aged 60 and older, which took place in 22 countries.
J&J and Bavarian Nordic make an exit
However, 2023 was not the year for some biopharmarmaceuticals. American company Johnson & Johnson (J&J) bowed out of the RSV vaccine hunt earlier this year. Its adult vaccine program was called off, as it decided to refocus its portfolio on medicines “with the greatest potential benefit to patients,” according to a press release. While its candidate’s phase 2 data looked encouraging, the ax did not come as much surprise since it had shelved other infectious disease programs and slashed its workforce, at the time.
And now, J&J, which had merged its infectious disease and vaccine units a few months ago, has done away with its research and development for the unit altogether, in another series of cuts.
Across the Atlantic, Danish vaccine maker Bavarian Nordic retreated from the development race in July, when its RSV program failed a phase 3 clinical trial. The efficacy endpoints were far lower when compared to the vaccines of Pfizer, GSK and Moderna. As a result, stocks took a plunge and its “growth expectations” were affected.
AstraZeneca wants a piece of the pie
Nevertheless, this flurry of approvals and setbacks has shaken the RSV vaccine research space, which seemed stagnant for a while. And now, AstraZeneca is the latest in line to take the leap. Icosavax’s candidate IVX-A12, is a combination vaccine containing virus-like particles (VLPs) that incorporate stabilized prefusion F proteins from RSV and hMPV viruses – another virus that causes respiratory diseases.
VLP vaccines mimic the way viruses tend to appear in the body’s immune system, often making them more potent than non-VLP vaccines, therefore, requiring fewer booster shots. They have also been known to cause fewer side effects than adjuvanted vaccines.
A phase 2 trial was found to elicit robust immune responses against both the viruses a month after the shot was given to adults aged 60 and over. As there are no combination vaccines against RSV yet, further data from the ongoing trial can help pinpoint where the multinational pharmaceutical company stands in the fight against RSV. And maybe, 2024 might see more RSV candidates hit the clinic to target a wider population as well.