COVID-19: Novavax, Johnson & Johnson, and where we are

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I had a tradition with a former “work spouse.” Whenever something truly annoying would occur, one of us would say out loud, “You know what I hate?” And the other would respond, “What do you hate?”

You know what I hate? I hate this pandemic. I hate the death, the misery, the numbers, the inane arguing, the lack of things to do, the Kansas City Chiefs being so freakishly good. Okay, maybe the last one has nothing to do with the pandemic. (As an aside, I love Patrick Mahomes, but could he do something wrong, like jaywalk, maybe kick a puppy? Something? Anything?)

My goal today is to decipher the slew of vaccine information that came out over the last few days and help you understand what it really means for this pandemic. (Did I mention I hate this pandemic?)

Setting the stage

Both Johnson & Johnson and Novavax released preliminary results of Phase 3 clinical trials late last week. I anticipate J&J will submit their vaccine for emergency use authorization this week, and that the FDA’s Vaccines & Related Biological Products Advisory Committee (VRBPAC) will review the vaccine next week. 

Novavax probably won’t be able to seek an EUA until late March because they need to finish enrollment for their U.S. Phase 3 clinical trial. I’ll go into more detail on each of these vaccines, how they work, and their full safety and effectiveness profiles when more data is released. For now, I will present the “top line” numbers, and then talk about vaccine effectiveness against variants.

The J&J data

J&J didn’t release a ton of data. Here are the main numbers: 66% reduction in the total number of cases of moderate and severe disease, 85% reduction in cases of severe disease, and no cases of COVID-related hospitalization or death in vaccine recipients. J&J did not release data on prevention of all cases of disease, nor did they release safety information except to say that the vaccine was well-tolerated. Unfortunately they also did not release data on the actual numbers of cases of disease, which, as I’ve discussed here and here, is important for a variety of reasons. 

The Novavax data

Novavax released preliminary results from their U.K. Phase 3 clinical trial, as well as preliminary results from a Phase 2b trial in South Africa. The U.K. Phase 3 clinical trial “only” included 15,000 participants and was 89.3% effective in prevention of all cases of disease. Unfortunately, due to the relatively small sample size, the number of cases of disease was small and the results had a very wide confidence interval. There were no cases of severe disease in vaccine recipients in the U.K. clinical trial. Novavax also stated that there was no difference in severe or serious adverse events in patients who received vaccine compared to those who received placebo.

A few various and sundry notes before more information on viral variants

The J&J vaccine was studied as a one-dose vaccination. That is, of course, more practical than a two-dose series. Based on what we know of immunology and the importance of booster doses, I “think” the topline clinical results would be better, and maybe closer to what was seen for the mRNA vaccines had the vaccine been designed as a two-dose series. The J&J press release noted that protection increased over time, which is expected, and also highlights one of the benefits of a booster dose, namely the ability to get to full protection faster.

Both the J&J and Novavax vaccines have more practical storage requirements than the Pfizer mRNA vaccine. The J&J vaccine storage requirements are very similar to the Moderna mRNA vaccine (shipped frozen but can be stored for a period of time in the refrigerator). The Novavax vaccine does not require any freezing, which is very convenient.

What about effectiveness against variants?

Neither J&J nor Novavax released specific effectiveness data by viral variant but they provided geographic data that gives us a good picture of things. Novavax included data from the U.K., the site of one of the notable variants, and both vaccines had data from South Africa, where the other notable variant was first identified.

Don’t take the percentage numbers I mention below as gospel. There are a great many details we don’t have yet, and the sample sizes are small. The numbers are only useful insofar as they allow us to draw general conclusions about these two vaccines’ effectiveness against these variants. 

The Novavax vaccine had essentially the same effectiveness against the U.K. variant as against previous COVID-19 strains (95% for the original COVID-19 strain vs. 85% against the U.K. variant). This wasn’t surprising because that variant has only a small number of genetic mutations in the spike protein. I say “essentially the same” because the trial was not designed to compare these effectiveness rates, so the fact that they are in the same ballpark just tells me there is unlikely to be a substantial difference in effectiveness. 

The story was not as positive for the South Africa variant, however. The J&J vaccine was 57% effective in South Africa, with a sample size of only about 6,600 patients. The Novavax vaccine South Africa trial was a Phase 2 trial, and therefore had a small number of participants, only 4,400. The Novavax vaccine was 49.4% effective against all cases of disease in South Africa.

My conclusions on the above J&J and Novavax data:

1. I am not concerned about the U.K. variant from a vaccine perspective.
2. I am comfortable saying the South Africa variant reduces vaccine effectiveness for the Novavax and J&J vaccines. I am not comfortable stating exactly how much the South African variant affects the Novavax and J&J vaccines, however, because of small sample sizes and the clinical trials weren’t designed to answer that question.

What about the Pfizer and Moderna mRNA vaccines?

The only data we have to inform our thinking of the effectiveness of the Moderna and Pfizer vaccines against the South African variant is in vitro studies looking at the ability of blood from vaccinated individuals to neutralize the variant. Although the concentration of antibodies needed to neutralize the South African variant was higher than that needed to neutralize previous COVID-19 strains, the South African variant was still readily neutralized by blood from mRNA-vaccinated patients. But what happens in a test tube does not necessarily translate to the human body. So what are the possible conclusions?

1. The mRNA vaccines may generate a more robust and diverse immune response than the J&J or Novavax vaccines. Although all of these vaccines use the same spike protein to produce immunity, it is possible that the creation of the spike protein from mRNA is more effective than the delivery mechanisms used by J&J or Novavax. There could also be dose-related and other reasons why the mRNA vaccines are more protective than the J&J or Novavax vaccines.
2. The mRNA vaccines are no better than the J&J or Novavax vaccines against the South African variant. Perhaps the in vitro test is not sensitive enough to predict the ability of these vaccines to neutralize the South African variant in the body? Or perhaps (although I think this highly unlikely) neutralizing antibodies are not the mechanism by which vaccinated individuals are protected?

My hunch (and my hope) is that the mRNA vaccines are more protective than the J&J or Novavax vaccines against the South African variant, but I can’t say that for certain. I will be on the lookout for more substantive data to draw a more firm conclusion.

What vaccine should you get?

First, I will not tell anyone they “should” get a vaccine. No one likes being told what they “should” do. I will simply give you the data and tell you what makes sense from my point of view.

Second, I cannot yet recommend either the J&J or Novavax vaccines because I have not seen the full data set. I waited to recommend the mRNA vaccines until I reviewed the full data presented to the FDA and CDC. I’ll follow the same rules here.

What does all this mean for the pandemic (which I hate)?

What this means is that we will soon have two more vaccines to help us get to a better normal. What would your response have been if at the end of March 2020 you knew that less than a year later we would have two vaccines in use, two more on the way, 31 million people vaccinated with one dose and 2.6 million people fully vaccinated, and that these vaccines could drastically reduce — if not eliminate — hospitalizations and death from COVID-19? I daresay that you, and nearly everyone else, would have been ecstatic.

I despise this pandemic. History served us a heaping pile of lemons. Now we’re being given the tools to make the best damn-tasting lemonade we can.  

Stay safe, and go make some lemonade.

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