We are truly fortunate. Less than two years into the deadliest pandemic in over a century, we already have three highly effective vaccines against Covid-19 available in the United States.
Now there’s another? Yes. And it may be an appealing option for some people who have yet to receive a Covid-19 vaccine or who might want to boost with something other than the currently available options.
Let’s talk about Novavax.
A new study published yesterday in the New England Journal of Medicine reports clinical outcomes for the 2-dose vaccine. If there weren’t already three other highly effective products on the US market, this study might have gone down as one of the great achievements of modern science and medicine. Instead, it’s almost an afterthought and practically nobody has even heard of it. Nevertheless, the outcomes appear similar to those seen among the now well-familiar Pfizer-BioNTech, Moderna, and Johnson & Johnson options. Compared to a placebo shot, Novavax’s effectiveness for preventing laboratory confirmed SARS-CoV-2 and symptoms of Covid-19 was found to be 90.4%. So far, data are only available for the first 3 months after the 2nd dose. Better yet, the effectiveness against moderate and severe disease was 100%. The data reflect nearly 30,000 volunteers recruited in the United States and Mexico.
This vaccine, and the study itself, has some advantages and disadvantages. Let’s go through them.
•Novavax is not a new technology. For the subset of people who remain convinced that the mRNA and DNA-based vaccines are not sufficiently vetted, Novavax offers an alternative, because it works differently than any of the vaccines currently on the market in the United States. In fact, it uses the same technology that many other existing vaccines have long used, including the “Tdap” vaccine against tetanus, diphtheria, and pertussis (“whooping cough”). Whether they realize it or not, many people have already received a vaccine that operates on similar technologies as the Novavax vaccine. The Novavax vaccine is a small “nanoparticle” that contains manufactured fragments of the SARS-CoV-2 spike protein (which are called antigens). That means that once those fragments are injected, our immune systems detect them and create antibodies which in turn lead to other longer-lasting responses and protection. That mechanism of action is in contrast to Pfizer-BioNTech and Moderna, which consist of tiny particles containing strings of genetic material (mRNA) which our cells then use to manufacture the spike protein. Johnson & Johnson works the same way, except instead of using nanoparticles as the delivery system, it uses a harmless virus to deliver the genetic code, and uses DNA instead of mRNA. So regardless of the fact that the mRNA and DNA vaccines are clearly safe, if Novavax gives peace of mind to a few holdouts, then let them choose it (once the US Food and Drug Administration authorizes it, which I expect might happen sometime early in 2022).
•The rates of severe systemic side effects were lower than the existing options. That might be appealing for some people. Those findings may also be appealing characteristics for people considering a booster. Mix-and-match boosting has some possible advantages. For me, the notion of a less uncomfortable experience this time around has enormous pull.
•Somewhat relatedly, another reason to welcome Novavax is that for the very small number of people who are truly allergic or have some other genuine contraindication to the other vaccines, this 4th option is nice to have.
•Supply chains. The fact is that in the United States, vaccine supply is likely to continue to exceed demand. If we do things right, we’ll anticipate this to continue. Rather than hoarding, the arrival Novavax should give us even more confidence that we can part ways with doses (of all products) that we know we won’t use and donate them to nations that desperately need them. Novavax can be stored at refrigerator temperatures, making the logistics easier in remote places that lack adequate freezer capacity. In short, more options and a more robust supply chains can spell equity tomorrow. But only if we act.
Neither advantage or disadvantage:
•Like the Pfizer-BioNTech vaccine, the 2-dose Novavax series was given 21 days apart. The advantage here is that recipients are likely to reach peak protection a bit sooner. But that may come at a cost. The slightly longer spacing between the two Moderna doses (28 days) is thought to be in part responsible for the slight longer-term protective edge it enjoys over Pfizer-BioNTech.
•This trial recruited volunteers from late December 2020 through mid-February 2021 and followed outcomes during the winter and spring. That means the data do not reflect the Delta variant era (let alone Omicron). It’s likely that if this study had been conducted during the Delta period, the outcomes might not have been as strong. That said, like the existing vaccines, it started with an exceedingly good record in protecting against moderate and severe disease (you can’t beat 100%). While we often forget, the Delta variant clearly lowered the other vaccines’ effectiveness for preventing infection, but protection against severe disease held up remarkably well. (As we all know, boosters have at least temporarily improved the protection against severe disease for older and immunocompromised people, but have not been shown to add any such benefit for people under age 40, and it remains “iffy” whether boosting those ages 40-49 provided adds any severe disease protection).
•Novavax trial participants could request to find out whether they had received the placebo or the actual vaccine. “Unblinding” can always influence the results of a trial, though it can work in any direction. For example, those who learn that they received placebo may have been more careful and limited their exposure to the virus. This could have lead to the appearance that the vaccine did not work as well as it actually does. Alternatively, those who learned they received the real thing may have become over-confident, and put themselves at a higher risk of infection, again possibly leading to the appearance of a weaker benefit for the vaccine.
•Follow-up data from this trial are limited. Because the trial happened right as the Pfizer-BioNTech and Moderna vaccines were becoming available to most people (remember the phased rollout?), researchers knew they could not ethically deny the actual Novavax vaccine to trial participants who had already received placebo. This means that at some point, everyone who had been assigned to receive the placebo had to actually get “the real thing.” While the outcomes look good 3 months out, we’d like to have seen a longer tail. Fortunately, those data should become available in the future.
•While the trial was large, at nearly 30,000 participants, Novavax has not yet been rolled out to millions of people. Therefore, any rare but important side effects have yet to be detected. (This is precisely what occurred for each of the 3 other options on the US market after millions of doses had been administered). The good news is that in this trial, almost everyone ultimately received the real vaccine, as explained above. That means the current Novavax safety data reflect approximately twice as many participants as we had to go on when the earlier trials were published, plus another 15,000 participants from a separate study conducted in the United Kingdom.
In a parallel universe, yesterday’s Novavax news would have been the story of the year, if not the decade. As it stands, we now have another powerful arrow in our quiver.
❓💡🗣️ What are your questions? Comments? Join the conversation below!
📬 Subscribe to Inside Medicine here and get updates from the frontline at least twice per week.