COVID antivirals are heavily marketed. It’s not clear how well they work

Expensive COVID-19 antivirals do not prevent hospitalisation or death for people who are vaccinated, a new but preliminary analysis of randomised controlled trials has found.

Hundreds of thousands of prescriptions for Paxlovid and Lagevrio were written last year, costing taxpayers more than $750 million.

Adverts for Paxlovid across the country warn “1 in 4 Aussies are at risk of severe COVID”, while doctors have been hit with a catchy jingle: “If it’s COVID – think PAXLOVID.”

The drugs are prescribed for people aged over 70, or those who are younger but have multiple risk factors; Lagevrio is meant to be restricted only to those who cannot take Paxlovid.

In a new meta-analysis of randomised controlled trials in people who are vaccinated and facing the current Omicron variant, presented at the Communicable Diseases & Immunisation Conference in Adelaide this month, neither drug reduced the risk of hospitalisation or death.

“I’m much less confident than I was [that] they still are having an effect on outcomes,” said Professor Allen Cheng, formerly a top COVID adviser and Victoria’s deputy chief health officer, who co-authored the study. “Whether antivirals are still worth their cost is not clear.”

Antiviral medication sold under Lagevrio’s generic name, molnupiravir.Credit: Washington Post

The decreased effectiveness is likely driven by the COVID vaccines dramatically reducing the risk that the virus poses, meaning there is less benefit from taking an antiviral, the researchers said. The current variant, Omicron, is also less lethal than the earlier Delta variant.

The meta-analysis is preliminary and has not yet been published.

Observational studies of the drugs included in the analysis concluded that the drugs halve the risk of hospitalisation, but the researchers are concerned that the results might be biased by differing trial designs. Generally, scientists look to randomised controlled trials for gold-standard evidence.

New Zealand stopped subsidising Lagevrio in 2024 due to concerns about its effectiveness.

Australia’s COVID-19 Evidence Taskforce recommends against using the drug, which costs $1102 a pack.

Despite that, Australian doctors gave out 315,000 scripts last year, plus another 243,000 for Paxlovid. Lagevrio and Paxlovid were the fifth and ninth-most-expensive drugs for taxpayers in 2023-24.

The taskforce only recommends Paxlovid for unvaccinated people. It offers a limited recommendation for those who have been vaccinated but are elderly and have multiple risk factors, while noting the evidence is unclear.

“In our systematic review, there were no randomised controlled trials conducted in vaccinated people since 2022 that reported a benefit from COVID-19 antivirals against hospitalisation or death,” said Dr Laura Edwards, a researcher at the University of NSW who led the study.

Doses of the antiviral drug Paxlovid.Credit: AP

“It is timely to re-evaluate whether the cost we are paying for these drugs is appropriate.”

It is plausible that the drugs may be useful for a small number of extremely high-risk people, who are elderly and have multiple risk factors, says Cheng. But this group is rarely enrolled in medical trials, making it difficult to work out the true efficacy.

“I’m not entirely sure there’s much benefit in that group. But there probably isn’t any harm done by it.”

Dr Gideon Meyerowitz-Katz, a senior fellow at the University of Wollongong, has published a cost-benefit analysis of Paxlovid. He said there was evidence of a small reduction in hospitalisation risk, making the drug still worth subsidising.

“I think that Australia has a very reasonable, pragmatic approach, prioritising high-risk individuals who will benefit and not paying for low-risk people who probably won’t.”

In a statement, Pfizer pointed to the first study of Paxlovid, which demonstrated an 86 per cent reduction in the risk of hospitalisation or death: “Real-world data collected during the Omicron period among high-risk populations who have received COVID-19 vaccinations reinforce the effectiveness of Paxlovid in preventing hospitalisations and deaths.”

Pharmaceutical company MSD, which sells molnupiravir (the generic name for Lagevrio), said it stood behind the drug.

The federal Department of Health said both antivirals were under review by the Pharmaceutical Benefits Advisory Committee, with results expected mid-2026.

Lagevrio and Paxlovid work by stopping the virus that causes COVID-19 from multiplying in our cells, theoretically giving the immune system a leg up against it.

The first studies by the drug companies found the two pills cut the risk of hospitalisation or death by about 50 per cent and 86 per cent respectively in unvaccinated people.

But Lagevrio’s 50 per cent effectiveness was seen only in a study that stopped halfway. When the full trial was analysed, whether it offered any benefit at all became debatable. A large independent study in 2022 also found it was probably no better than a placebo.

A study published by Pfizer last year concluded Paxlovid’s protective effect in vaccinated patients, including those at high risk, was so small as to not be statistically significant.

That study began in 2021 but was only published in 2024.

Research conducted by the Grattan Institute late last year found that wealthier Australians were far more likely to be prescribed COVID antivirals than those at the bottom of the income ladder, despite people living in disadvantage typically having much greater risk factors for severe disease.

“Essentially, like so many things in our healthcare system, the treatments and services weren’t going to the people who need them most,” said Peter Breadon, the institute’s health program director.

Nearly all Australians have either been vaccinated or survived a COVID-19 infection, meaning there is less benefit from antivirals. And the Omicron variant is less likely to hospitalise or kill a patient than the preceding Delta variant.

Professor Allen Cheng, who was once a top COVID adviser and is now director of infectious diseases at Monash Health.Credit: Nicole Reed

“COVID is a different disease to what it was,” said Cheng, who is now director of infectious diseases at Monash Health.

“[Patients] don’t get pneumonia and lung white-out, generally. It’s almost like we’re doing a study in a different disease, which is making it difficult to work out how relevant … what we found out early on [is] to what we know now.”

This stark difference shows up in Pfizer’s studies of Paxlovid.

In Pfizer’s first study, involving unvaccinated people, 7 per cent of patients given a placebo ended up in hospital and 13 died. In the second study, which involved vaccinated people, just 1.6 per cent of the placebo group were hospitalised.

“For young, fit and healthy people, antivirals are not going to do much. You’re at pretty low risk,” said Cheng. “For older people – those over 65 or 70 – or people who have other medical issues, that’s one they should go and see their GP.”

Liam Mannix travelled to the Communicable Diseases & Immunisation Conference as a guest of the conference and an unpaid speaker.

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