The recent decision by regulators to approve the antiviral agent Paxlovid for use in the UK adds a formidable new weapon to the arsenal of treatments for Covid-19. Pfizer says the drug has almost 90% success in preventing severe illness in vulnerable adults if taken soon after infection occurs. Paxlovid is one of a growing repertoire of antiviral medicines – which also includes Merck’s agent Molnurpiravir – that can be given to people who have contracted the disease. Crucially, antivirals – which disrupt a virus’s ability to replicate inside an infected cell – provide hope that infected vulnerable individuals, including the very elderly and those with compromised immune systems, can be kept out of hospital.
It has taken two years of research for the first antivirals to be approved, with drugs becoming available more than a year after the first Covid vaccines were given in the UK. So why has it taken so long, comparatively, for effective antivirals to be developed? And what role will they play in the UK, which now has broad vaccine protection against Covid?
Vaccines come first and antivirals afterwards when most predictions suggested it would be the other way around. Why?
“I expected antivirals would be in use before vaccines, I admit,” says Tom Fletcher of the Liverpool School of Tropical Medicine. “What actually happened reflects the unbelievable speed of the vaccine research and the failure of the first tranche of antivirals that were tested.”
At the start of the pandemic, most effort went on considering repurposed drugs – ones used to treat other illnesses but which had established safety profiles – in order to treat Covid-19.
“However, none of these repurposed antivirals have worked,” added Fletcher, who is also a member of the UK Agile trial that tries to find new Covid treatments. “After that, scientists focused on new antivirals specifically designed for Covid-19. Normally, drug development pipelines take five to 10 years at best. These timelines have been accelerated but it has still taken two years to get to this point.”
How will the new antiviral drugs be used?
Doctors have learned a great deal about treating Covid-19 patients in hospitals. “They have greatly improved outcomes for seriously ill patients – through knowing when to turn them, administer dexamethasone or give them intravenous antibodies,” said Ruth McKernan, chair of the BioIndustry Association. “But prevention is better than cure. So keeping people out of hospital is the real goal here and the new oral antivirals should be invaluable in achieving that.”
Once a vulnerable person – someone who is old or has a compromised immune system – becomes infected, they will be given Paxlovid or Molnurpiravir and that, it is hoped, will prevent them becoming so sick that they need to go to hospital, which is good news for the patient and for the NHS.
What still needs to be discovered about antivirals?
“Clinical trials of antivirals began shortly after Covid first arrived, so they were tested almost totally on non-vaccinated patients,” said Eddie Gray, chair of the UK government’s antivirals taskforce. “Today, we have a population that is largely vaccinated. So we need to show that antivirals still have real benefits for these people.”
This data will be provided by an Oxford University study, called Panoramic, which is assessing the impact of antivirals on vulnerable but vaccinated people in the UK. “Panoramic is very important,” added Gray. “It’s the mechanism by which we will work out the magnitude of the benefit our vaccinated population gets from antivirals. We expect results next month.”
What lessons are there for treating Covid from other use of antivirals?
“These drugs operate by disrupting the way that a virus produces copies of itself inside our cells and we have seen this process being deployed in antivirals that deal with other diseases,” added Gray. “One implication is that they are likely to be very effective in tackling new variants of Covid.”