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Image: Tina Tiller
Image: Tina Tiller

ScienceNovember 9, 2021

Siouxsie Wiles: Covid-19 pills are great – but we still need the vaccine

Image: Tina Tiller
Image: Tina Tiller

Last week the first oral anti-Covid-19 pill was approved in the UK. Then Pfizer reported that its pill worked too. Siouxsie Wiles explains what these new treatments are, why we need them, and why you should still get vaccinated.

The Medicines and Healthcare Products Regulatory Agency in the UK recently became the first in the world to issue a temporary authorisation for Merck’s antiviral drug molnupiravir (which will be sold as Lagevrio) to be used to treat mild to moderate Covid-19 in adults. They’ve ordered 480,000 treatments and say it’ll only be given to people with at least one risk factor for severe illness.

The UK desperately needs something as hospitalisations and deaths are rising again and winter is on its way. Just last week the CEO of Addenbrooke Hospital in Cambridge said that his hospital is “ceasing to function as a hospital” and that they’ll soon need to send patients to Birmingham or London. Hot on Merck’s heels is Pfizer, which has just announced that it also has an antiviral drug, paxlovid, and it may be even more effective than molnupiravir.

Current antiviral treatment for Covid-19

There is already one antiviral drug, remdesivir, that is being used to treat people with Covid-19, but it has its problems. Remdesivir was developed by Gilead Sciences and works by interfering with the virus’s ability to make copies of its genetic material. It was originally developed to treat hepatitis C and respiratory syncytial virus (RSV). Unfortunately, it turned out remdesivir didn’t work against those viruses so it was then repurposed to see if it would work against Ebola. That was more successful but in clinical trials it turned out not to be as effective as other available treatments.

When the pandemic hit, Gilead Sciences tried again and found remdesivir can stop the Covid-19 virus from replicating in the lab. But the results from the clinical trials have been disappointing and a recent review concluded that remdesivir probably makes little or no difference to deaths or the amount of time patients spend on a ventilator. One of the big reasons for this is that remdesivir isn’t available in pill form. Instead, it must be given intravenously as three infusions over three days. That means people are only getting the drug when they are admitted to hospital and by that time, the virus is already rampaging around their body. Gilead recently said that remdesivir reduced hospitalisations by 87% in high-risk patients if they were diagnosed and treated early.

The data from their trial hasn’t been released yet but it’s clear that early treatment with an intravenous drug is going to be a logistical challenge.

What’s different about molnupiravir and paxlovid?

The big difference between these two new drugs and remdesivir is that molnupiravir and paxlovid are available in pill form. That means they can be given much more easily and much earlier in infection. Molnupiravir is another one that interferes with the virus’s ability to make copies of its genetic material. Paxlovid is what’s known as a protease inhibitor and was designed specifically to block the Covid-19 virus at the step before it starts to make copies of its genetic material.

Trial results for molnupiravir and paxlovid haven’t been published yet either but Merck has said the interim results of its phase three trials showed that molnupiravir resulted in a 50% drop in risk of hospitalisation or death for patients with mild to moderate Covid-19 who were at risk of poor outcomes. Pfizer has also issued a press release about its phase three trial results for paxlovid, saying its drug showed an 89% reduction in risk of hospitalisation or death in similar patients.

It’s quite fascinating taking a closer look at the numbers. Both trials were carried out at multiple sites around the world, though Merck says about half of its trial participants were in the USA. In the Merck trial (NCT04575597), 28 out of 385 people taking molnupiravir ended up in hospital. That’s 7.3%. For the placebo group it was 53 out of 377, or 14.1%. Twenty-nine days after treatment, none of the patients taking molnupiravir had died compared to eight in the placebo group. In the Pfizer trial (NCT04960202), three out of 389 people taking paxlovid were hospitalised, or 0.8%. For the placebo group it was 27 out of 385, or 7%. For the placebo group, that’s half the rate of the Merck trial. Why were the hospitalisation rates so different? Deaths were very similar, with no one dying if they were given paxlovid within three days of their symptoms starting, compared to seven deaths in the placebo group. It would be good to see all this data properly peer-reviewed and published.

Pfizer also have other trials of paxlovid on the go, including testing whether it works for otherwise healthy people or to prevent infection in people who know they’ve been exposed to Covid-19. Paxlovid was specifically designed to target the virus responsible for Covid-19, and Pfizer says its lab-based studies show it is active against all the current variants of concern as well as other known coronaviruses. Hopefully by that the company means the one that causes Middle East respiratory syndrome (Mers) rather than just the ones that cause the common cold, as Mers is even more deadly than Covid-19 but thankfully doesn’t seem to be transmitted well between people.

Why we still need to get vaccinated

It is great news that we may soon have not just one but two new drugs to treat Covid-19 in its early stages. It’s clear the companies are hoping these treatments will become something that people can take at home either when they’ve been diagnosed with Covid or have been exposed to the virus. We certainly need treatments like these given the vaccines don’t protect everyone who gets one. But they shouldn’t be handed out like sweeties, for a reason I’ll explain in a moment, and they definitely don’t change the need for everyone to get vaccinated. The vaccines are doing a really good job of preventing people from catching Covid-19 in the first place. The data is showing that protection wanes after six months or so, at least in older people, but hopefully that’ll be improved by having a booster dose.

I’ve written a few times about how the Covid-19 variants have arisen. If you need a reminder, check out Toby Morris’s awesome graphic on the subject below. In short, it happens because of random mutations that occur when the virus replicates. That same process could also lead to variants arising that are resistant to these new drugs. The more the drugs are used around the world, the more chance we have of that happening. This is why we are running out of antibiotics to treat bacterial infections. In saying that, using the drugs in combination could help stop resistance emerging or at least slow it down. But we’ll need to see if they are safe to take together.

So, in summary, the news of two new anti-Covid pills is awesome, but please don’t let this stop you getting vaccinated.

I just want to end with one thing that made me really angry about Pfizer’s announcement. On its press release there is a section about its commitment to “deliver safe and effective antiviral therapeutics as soon as possible and at an affordable price”, it says, “for all people”. It says the company will do this for paxlovid by charging more to high and upper-middle income countries. The release also says it is investing up to approximately US$1 billion to support the manufacturing and distribution of paxlovid, “including exploring potential contract manufacturing options to help ensure access across low- and middle-income countries”.

Here’s my question: Why the hell aren’t they also doing this for the Covid-19 vaccine they make?

Keep going!