What is Pfizer's antiviral pill and can it cure COVID?

Two years after the first reported cases of COVID-19 and one year after the first vaccine was administered, there’s new hope for ending the pandemic, in the form of antiviral pills that can be taken at home.

Drug maker Pfizer's recently announced antiviral COVID-19 pill - which would be sold as Paxlovid - showed promising results, with a near 90% efficacy in preventing hospitalizations and deaths in high-risk patients.

"These are very exciting results," Paul Sax, a professor at Harvard Medical School, told Reuters.

Lab data also suggested the drug retained its effectiveness against the fast-spreading Omicron variant, Reuters reported.

Whereas previous antiviral treatments for COVID-19 had to be administered intravenously in hospital, the new antivirals are heralded as a ‘game-changer’ in treating the disease, because people can take them at home.

So, what other antiviral pills are in the works, how do they work, who can use them and how effective are they against COVID-19?

The EU has just cleared Pfizer's antiviral COVID pill for use as soon as possible after diagnosis - or within five days of symptoms starting - among patients suffering severe forms of infection. But the drug can’t be used if the patient requires supplemental oxygen, Reuters reports.

The advice from drugs regulator the European Medicines Agency comes despite the medicine not having completed its full review for regulatory approval.

Paxlovid works by blocking the SARS-CoV-2 virus’ protease - a viral enzyme that cuts up the long virus polyprotein into smaller pieces in order to replicate.

Pfizer expects the U.S. Food and Drug Administration (FDA) to authorize Paxlovid for use in high-risk patients soon and is in talks with the UK and “most of the major regulatory agencies globally”, Pfizer Chief Scientific Officer Mikael Dolsten told Reuters.

In November, Pfizer released interim results showing the treatment was around 89% effective at preventing hospitalizations and deaths in a trial of 1,200 people. The latest results included an additional 1,000 people.

These COVID pills are taken with an older antiviral called ritonavir every 12 hours for five days starting soon after the first symptoms appear.

No one who received the oral medicine died, but there were 12 deaths among those who received a placebo drug.

"It's a stunning outcome," said Dolsten. "We're talking about a staggering number of lives saved and hospitalizations prevented. And, of course, if you deploy this quickly after infection, we are likely to reduce transmission dramatically.”

Pfizer expects to have 180,000 treatment courses ready this year and plans to make at least 80 million more in 2022. It has also agreed to allow other manufacturers to supply versions of the COVID pill to 95 low- and middle-income countries through a licensing agreement with international public health group Medicines Patent Pool. However, it could be well into 2022 before generic manufacturers start producing the drug.

On 4 November 2021, Merck’s oral antiviral became the first COVID-19 treatment to receive approval globally, when the UK’s Medicines and Healthcare products Regulatory Agency deemed it to be “safe and effective at reducing the risk of hospitalization and death in people with mild to moderate COVID-19 who are at increased risk of developing severe disease”.

“Today is a historic day for our country, as the UK is now the first country in the world to approve a COVID pill that can be taken at home for COVID-19,” said UK Health and Social Care Secretary Sajid Javid.

“This will be a gamechanger for the most vulnerable and the immunosuppressed, who will soon be able to receive the ground-breaking treatment.”

However, since then, a second round of results has shown a stark difference in efficacy: down to 30% from an initial 50%.

The initial study took place between May and August, with 762 people given four pills twice a day for five days. In the second study, between August and October, 646 people received the same treatment. In both studies, treatment started within five days of symptoms starting.

But, while for the first group, the chance of hospitalization or death dropped by half compared with the placebo group, there was almost no difference in outcome between the patients on molnupiravir and those on the placebo drug in the second group.

On 30 November, Nicholas Kartsonis, senior vice-president of clinical research at Merck, told the FDA advisory committee the company couldn’t explain the disparity between the results.

Molnupiravir, which would be sold as Lagevrio, works by masquerading as one of the key molecules in the RNA strand needed to replicate - and tricking the virus into making genetic errors as it copies itself, to the extent it can no longer function.

However, safety concerns have been raised by some scientists about the potential for birth defects from the Merck drug, as well as worries it could cause the virus to mutate, according to Reuters.

There are other much-needed antiviral drugs in development, says Patrick Jackson, Assistant Professor of Infectious Diseases at the University of Virginia.

Around 1,400 COVID-19 drugs and vaccines were being developed as of 16 December, according to PharmaIntelligence, with 17 having been registered.

Those in development include an oral form of the first COVID-19 drug, remdesivir and long-acting injectable monoclonal antibodies.

Jackson says: “Researchers are also working on repurposing existing drugs to treat COVID. Inhaled steroids like budesonide and an antidepressant called fluvoxamine are particularly promising.”

Only time will tell how much of an impact these treatments will have - and whether they can help to bring the pandemic to an end.