Two New Antivirals Targeting COVID-19


Science-Based Medicine

Steven Novella on November 10, 2021

There are two new drugs on the horizon that actually work against COVID-19.

Recent weeks has seen the announcement of two new drugs that could potentially treat acute COVID-19 infections. The UK approved molnupiravir by Merck, which will now be tested in clinical trials and likely licensed early next year. Meanwhile, Pfizer a day later announced Paxlovid, which it says is 89% effective in preventing hospitalizations and death, and now seeks FDA approval. If one or both of these antiviral drugs works out, what could this mean for the pandemic?

Right now there are several tools we have for tackling the COVID pandemic. One is public health measures to reduce spread of the disease – masking, social distancing, avoiding crowds, especially in indoor spaces, isolating if exposed or sick, testing, and contact tracing. Together these methods have been critical to minimizing the spread of COVID, but they are not enough on their own to stop the pandemic or prevent spikes in infection. There are also, of course, vaccines, which reduce the chance of contracting the illness if exposed, reduces the severity of illness if you do get it, and reduces the chance of passing on the virus to others. Vaccines are rightly considered our best hope for ending the pandemic, or at least having life return mostly to normal.

We also need to treat people who become sick with COVID despite preventive measures. Here also there are two types of interventions: supportive, and anti-viral. Supportive measures reduce the symptoms and complications of infection, and keep people alive until their immune system can fight off the infection. Using steroids like prednisone has turned out to be one of the most effective measures, because the most severe outcomes from COVID are likely due to the body’s immune reaction to infection, the worst being so-called cytokine storm. It may also be necessary to intubate patients with severe illness so that a ventilator can breathe for them until their lungs recover, although it was discovered that delaying intubation as long as possible may improve outcomes. A March 2021 systematic review, however, found no difference in all-cause mortality between early and late intubation, so at least there is no advantage to early intubation and no risk from delay.

The high-tech treatment for COVID has been some type of immunoglobulin treatment. This can be intravenous immunoglobulin (IVIG), which is simply pooled antibody proteins from many donors. It can also be hyperimmune gamma globulin, which is taken from donors who have had COVID-19 (convalescent plasma), and is considered more effective than regular IVIG. There are also monoclonal antibodies, which are one type of antibody against SARS-Cov-2 (usually the spike protein) which have to be produced in a bioreactor (not taken from people). Research into all of these antibody treatments is ongoing, but overall they have some efficacy in reducing the severity of illness. However, they are expensive and of limited availability, and so by themselves are not going to have a large impact on the pandemic.

Finally, we have therapeutic treatments, specifically direct anti-viral drugs. This treatment option for COVID has so-far eluded medical experts. There have been many proposed treatments, the most famous (or infamous) have been hydroxychloroquine and ivermectin. We have discussed these two drugs extensively here so I won’t go over them again, except to say that neither drug has been shown to be an effective treatment for COVID-19 in clinical trials, and neither is recommended for use. They have, however, become very politically controversial. As an aside it does demonstrate how easy it is for those with political or anti-science agenda to flip the script as needed. In this case some of them reject a safe and effective preventive measure (vaccines), in favor of an unproven pharmaceutical treatment for the disease once it occurs.

Despite all the controversy over the past almost two years, we may now finally have two antiviral drugs that actually work. The data for Pfizer’s Paxlovid is particularly impressive, if it holds up to review. They report the result of a phase 2/3 double-blind placebo-controlled trial in patients with COVID who were not hospitalized:

The scheduled interim analysis showed an 89% reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint); 0.8% of patients who received PAXLOVID™ were hospitalized through Day 28 following randomization (3/389 hospitalized with no deaths), compared to 7.0% of patients who received placebo and were hospitalized or died (27/385 hospitalized with 7 subsequent deaths).

This is a good absolute and relative risk reduction, essentially making COVID a much less deadly illness. If used widely this treatment would significantly reduce the COVID burden on the hospital system. While the data was presented as 89% relative risk reduction in hospitalization or death, it should be noted there were zero deaths in the treatment group (compared to 7 in the placebo group). The FDA must now review this data and determine if they will give the drug an emergency use authorization (EUA) and start the process for full approval. They may also ask for more data, which would certainly come in any case as researchers track the results of treatment.

Merck’s drug, meanwhile, was shown to have a 50% reduction in hospitalization – from 14% to 7%, with deaths decreased from 8 to zero. This is a similar outcome, but it’s hard to do a direct comparison because of different populations and methods. But it’s safe to say that both drugs are highly effective.

Hopefully by early next year one or both of these drugs will be available to treat patients newly diagnosed with COVID-19 (whether under an EUA or as part of ongoing clinical trials). What does this mean for the pandemic? This is, potentially, huge news, and could be a game-changer. In the best-case scenario where both drugs are confirmed to be safe and highly effective, this would mean that the lethality of COVID-19 is dramatically mitigated, reducing hospitalizations and deaths. This would be a very welcome respite for overburdened hospital systems and workers, which will have a significant downstream benefit to health care overall. We may also finally start to see the mortality rate for COVID start to dramatically come down.

The vaccines have clearly been the most important medical development for tackling this pandemic, and this will remain true. Vaccines are necessary to reduce spread and avoid spikes in illness, and to allow life to return to normal. But it also increasingly looks like, despite the availability of vaccines, we are going to have to live with COVID-19 for the foreseeable future. It will likely become endemic like the flu. Having effective anti-viral treatments will therefore be essential to reducing the health burden of this virus.