But Does It Work?

When Paxlovid was first approved for use, I looked up the trial data. This is almost always quite easy to do but as most folks don’t learn how to read medical studies in high school or even university, interpreting the findings can be difficult. In the case of Paxlovid, it wasn’t difficult at all for a number of reasons.

First, the EPIC HR trial tested Paxlovid in unvaccinated adults. This is fine if you are going to restrict Paxlovid to unvaccinated adults, but, if the drug is going to rolled out in the western world where almost every adult has had at least two Covid vaccinations, there’s a problem. These are two different populations. This is medical science 101 and understandable by anyone of average intellect. Subsequently, of course, Paxlovid was made available to vaccinated adults, and, foreshadowing here, we should have some idea how that is going to end.

Secondly, while Paxlovid in unvaccinated adults did show a treatment benefit, the effect size was modest. The primary outcome was Covid related hospitalisation or death from any cause over the full 28 day study. Death from any cause is an interesting endpoint and one would hope but I would not trust, that “death from any cause” did not include random events like bus accidents etc. In the full intent to treat analysis death from any cause in the placebo group was 1% versus 0% in the treatment group. Not much can be concluded from this as the signal to noise ratio is too high given the paucity of “events” (death from any cause is the event). Six percent of patients in the placebo group were hospitalised for Covid 19 versus just under 1% in the treatment group (0.77%). This is certainly in favour of Paxlovid but again, the numbers are small in both groups. Either way, this is not a blockbuster drug by any stretch of the imagination and given that many commonly used medications are contraindicated in conjunction with Paxlovid (check the list it will surprise you), Paxlovid should be approached with caution, as should all newly released drug treatments.

Thirdly, it’s also worth noting that the original EPIC HR trial was done when Delta was the main Covid variant in circulation and more recently circulating variants are producing considerably less severe disease.

In April of this year, the EPIC SR trial was published to remarkably less fan fare and remarkably less action by public health officials. This trial was open to both vaccinated and unvaccinated individuals and people at no risk of severe disease from a Covid infection. This is the real life population of people who are likely to take Paxlovid which makes determining whether or not Paxlovid has any efficacy in this population of paramount importance. In the EPIC SR trial the primary endpoint was “time to sustained alleviation of all targeted Covid-19 signs and symptoms.” This is an imprecise endpoint (the data is self-reported) but one that is commonly used in anti-viral drug studies. Covid related hospitalisation and death were secondary endpoints.

There is no point going into detail about the EPIC SR trial because the conclusion says it all: “The time to sustained alleviation of all signs and symptoms of Covid-19 did not differ significantly between participants who received nirmatrelvir–ritonavir (Paxlovid) and those who received placebo.” There was also no difference between Paxlovid and placebo on either of the secondary endpoints (hospitalisation or death).

As of May 2024, we have not seen any statements from our public health officials that address the newest data on Paxlovid. In fact, the latest press release I could find was basically a publicity campaign for both Paxlovid and the Albenese Government advising that more people would be eligible for Paxlovid. You get to decide if you think this is appropriate and representative of the currently available science. Of course, you should also carefully read the trial data, consult your own physician, and make your own decision based on what is important to you.

One day I’ll write a long post about why I, among so many other citizens of the world, have lost faith in public health and our regulatory agencies. You could consider this a first instalment.