Breaking Vaccine News: Pfizer/BNT Phase III Interim Data I

5 min readNov 9, 2020

News broke this morning that the Phase III clinical trial of Pfizer/BioNTech’s mRNA vaccine candidate BNT162-b2 has achieved over 90% efficacy in the first (and only) interim analysis. The independent analysts looked at 94 cases of symptomatic COVID-19. [1–3]

The efficacy describes the relative reduction in disease for the vaccinated patients relative to the ones who received placebo. Patients who were vaccinated were 10 times less likely to contract SARS-CoV-2. [4]

Many experts were setting the bar for an effective vaccine at 70–75%. Therefore, this first estimation is extremely encouraging. Notably, the companies involved are not the ones analysing the data.

The unfortunate (but fair, as the trial is ongoing) part of all this, is that once again we learn the news via press release and cannot see the data yet. There are a couple interesting points that still need to be examined. [5]

The first is whether vaccination leads patients who do contract SARS-CoV-2 to experience more mild illness. In the best possible scenario this is true; a realistic expectation might be that this is true for a fraction of patients.

A second point is whether the few patients who were vaccinated but still came down with COVID-19 are still able to transmit the virus. If yes, how infectious were they compared to unvaccinated infected patients and for how long? Again, best case here is that they do not transmit and a more realistic expectation is that they do, hopefully at a reduced rate.

Finally, this trial obviously examined symptomatic patients, what happens with asymptomatic individuals? Here speculation can run wild.

In terms of side-effects, this candidate has been characterised and covered in the past on this blog. Standard reactions include sore arms, fever, fatigue etc. Well worth it in exchange for relief on the health system or compared to a visit to the ICU. Of note, this trial has raised no safety concerns so far. For longer term safety data, there is no alternative but to wait longer. [6]

The AstraZeneca/Oxford trial has experienced a couple events that have paused the trials (both the phase I/II in the summer & the ongoing phase III). They were assessed as being multiple sclerosis (unrelated to vaccine) and transverse myelitis (also unrelated?). The trial has resumed. [7,8]

Even if these events were related to that vaccine (they are not according to the trials), they would most likely be due to the method of delivery of the vaccine, which uses a different virus, called adenovirus. Therefore, these events are unlikely to be seen in the different platforms like mRNA (Pfizer/BioNTech & Moderna) or recombinant spike (Novavax & GSK/Sanofi). [9,10]

An important and valid concern for this specific vaccine candidate is shipping and storage. Generally for shipping it requires cryogenic temperatures (-78 °C). However, BioNTech has said they have data showing storage stability at 2–8 °C for 5 days at least, potentially up to two weeks or longer. [11]

All in all, distribution is going to be a massive challenge. Pfizer and BioNTech have announced that they have 50 million doses available for 2020, corresponding to 25 million patients. They also intend to manufacture another 1.3 billion doses (read 650 million patients) by the end of 2021. The dosing regimen, with two doses 21 days apart, is another challenge which complicates things.

The biggest reason that the news of vaccine efficacy is important is not because this particular vaccine candidate is going to change everything overnight. Instead, it is because it completes the puzzle that shows the approach towards developing the vaccine to be successful.

Almost all candidates target the spike protein in one way or another. All have been shown to raise neutralising antibodies against spike, both in animals and in humans. These inhibit viral entry to cells in vivo. In addition, some of them have been shown to stimulate T-cells. None have shown serious safety concerns in the timeframe in which they have been studied. Now, we have evidence that one of these candidates (which shares a common approach with almost all other candidates) is effective at protecting patients from infection. [9,12–19]

There are a few more scenarios that could still in principle play out which could possibly throw off all the vaccine business.

To start, one would be extremely short-lived immunity. This is a highly unlikely scenario, since out of more than 50 million confirmed (and many more unconfirmed) cases of COVID-19, we have only 20 documented cases of reinfection. In addition, the antibodies generated by the vaccines appear to be comparable (if not better than) those raised by recovering from the disease. [20]

Another scenario is antibody-dependent enhancement, where the antibodies generated actually make the disease worse. However, this is a scenario that all developers of vaccines have been extremely vigilant about and has not been observed even once so far. [21]

Lastly, it is conceivable that some longer term adverse events will be associated with these vaccines. Things along the lines of the transverse myelitis discussed above. Based on the studies so far, these would appear to be extremely rare. Even if they would be found later on, their incidence will be extremely low. A rate of adverse events of 1 in 500,000 would in theory make about 16,000 people worldwide (if everyone on the planet were vaccinated) very ill. Comparing that to the theoretical ~40,000,000 people who would likely die if the vaccine was not used, there is no question if the vaccine should be rolled out.

Note: the above numbers are pure speculation and very back-of-the-envelope. They serve only to put the magnitudes in perspective. The number of fatalities from COVID-19 assumes a global population of 8 billion, IFR 0.07 and 70 % threshold for herd immunity.

So to reiterate, the big news here is that the approach has now been demonstrated to work, not that this vaccine candidate is necessarily the best one, or the one that will or should be most widely employed. Hopefully, more candidates will be successful and we will see rollout of many at once so that the pandemic may end as soon as possible. There is now a path forward which may allow the world to welcome 2022 largely pandemic-free.

SARS-CoV-2 was first identified in January 2020. Less than a year later we are already seeing successful phase III trials and we are talking about vaccine distribution. This is historic and nothing short of incredible.

Hail science.

References

Breaking Vaccine News: Pfizer/BNT Phase III Interim Data I

Written by Michael Bogdos