Britain’s National Health Service (NHI) has started treatment the monoclonal antibody treatments sotrovimab and molnupiravir to reduce the hospitalisation of COVID-19 patients, and is awaiting approval for use of Merck’s for Paxlovid pill.
Sotrovimab (Xevudy), developed by GlaxoSmithKline, is initially being given only to clinically vulnerable people, like cancer patients, organ transplant recipients and other high-risk groups. It should be taken within five days of infection from COVID.
The dispensing of Sotrovimab came a fortnight after the NHS announced the distribution of another antiviral, molnupiravir, which was first developed as an influenza treatment, to 10,000 COVID patients across the UK.
Molnupiravir (Lagevrio) was developed by Merck; in November, the UK became the first country to approve its use against COVID. It is being given out as part of a trial with Oxford University. Participants, most older than 50, will take eight pills each day, for five days, and will be asked to chart how they feel for 28 days in a diary.
Sotrovimab is only being given to patients in vulnerable groups, while the UK is still waiting for approval for Paxlovid, an antiviral pill developed by Pfizer. The UK has ordered 250,000 doses of this drug, but it hasn’t yet been approved in Britain.
How effective are the new antivirals?
Molnupiravir was trialled in a US study last year (anchored at Atlantaʼs Emory University but mostly carried out in Latin America). The drug cut the risk of hospitalisation in half when compared with a placebo.
Paxlovid (not yet approved in the UK) looks even more effective, cutting the risk of hospitalisation and death by 89%.
Sotrovimab, meanwhile, reduced the risk of hospitalisation and death by 79% in high-risk adults with COVID, according to one clinical trial quoted by the government.
Will they work against new variants?
Yes, antivirals like Molnupiravir and Paxlovid are likely to work against most variants, scientists say in an article in the Daily Telegraph. Antivirals normally target the genetic material in the middle of a virus particle, which generally doesn’t change from mutation to mutation. This means they will probably perform well against every variant of Covid, explains Penny Ward, an expert in pharmaceutical medicine and visiting professor at King’s College London.
The answer is less certain for monoclonal antibodies like Sotrovimab, says Ward: “The monoclonal antibodies were designed against the original Wuhan strain. And so the same problem emerges with a monoclonal antibody as we have with the vaccines, which is this question over whether the antibody itself will continue to bind the new variant.”
Vaccines, in contrast, usually target the virus’s spike protein, which changes much more frequently. This is why vaccines have become slightly less effective with each new variant of concern.
Will antivirals keep patients out of hospital?
Throughout the pandemic, UK policymakers have kept a close eye on hospital numbers, thought to be the most important metric used by ministers to decide on issues like lockdown.
The beauty of the new generation of antivirals is that they act early, when a patientʼs symptoms are still mild. If effective, they prevent the patientʼs symptoms from escalating, meaning they donʼt have to go into hospital. You simply swallow the capsules when you have the sniffles, and hopefully the sniffles are the worst it gets.
This makes them far more exciting than other drugs that have been used against COVID, like Remdesivir, an antiviral developed against hepatitis-C, and dexamethasone, an anti-inflammatory steroid that soothes the bodyʼs immune response. Generally, both of those drugs are only used once a patient is already seriously ill in hospital.
Will antivirals be widely available?
The new COVID pills look promising, but doctors are still unsure how widely they should be given out. The new generation of antivirals work best if given early. Molnupiravir, for example, should be given within the first five days, and ideally in the first 48 hours, before the virus has had a chance to spread.
Some, like Harvard Universityʼs Professor Michael Mina, think the pills should be driven to a patientʼs home in an Uber-style service. Others think they should be available over the counter at pharmacies.
But Griffin doesnʼt agree. He hopes the pills arenʼt “given out like sweeties”, telling The Telegraph: “These are new medications, you definitely want clinical oversight. We do that for HIV [and] hepatitis-C. They do have the potential to have side-effects, or to mix with other drugs.”
Are there any risks with antivirals?
There is some concern about the virus mutating in response to antivirals. An animal study at the University of North Carolina found that Molnupiravirʼs strategy of replication (where it tricks the virus into making copies of the wrong thing) could theoretically accelerate the mutation of the virus inside our cells, creating yet more dangerous COVID variants. In theory, the higher the number of people prescribed the drug, the higher the chance of a dangerous mutation – “like lottery numbers”, says Griffin.
Ideally, say Griffin and others, COVID patients would be given several antivirals at the same time, to minimise the chance of an antiviral-resistant virus strain escaping the body.
This is already the standard approach to HIV, against which antivirals scored an impressive success in the 1990s. Now, most HIV patients in the UK take several antivirals daily to minimise the chance of the virus becoming resistant to one of the medicines and then escaping the body by infecting somebody else.
According to manufacturer Merck, the virus already does a perfectly good job of creating variants when allowed to spread freely, therefore the risk is overblown, it says.
The Telegraph article – Is the new Covid drug the answer to our prayers? (Restricted access)
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Merck’s COVID antiviral pill may halve the risk of hospitalisation and death
Pfizer to deliver generic version of its COVID pill to 95 countries
Merck’s COVID pill narrowly wins FDA panel's 'yes' vote
Pfizer’s anti-COVID oral tablets show robust efficacy
Reduction in infectious SAR-CoV-2 with molnupiravir — Small US study
Promising early findings from Merck/Ridgeback Phase 2a trial of oral COVID-19 therapeutic