Antiviral pill: How close are we to a drug to treat Covid-19?

Scientists seek breakthrough in effort to ease virus symptoms and speed up recovery times.

A woman waiting to receive her Covid-19 booster shot at a vaccination centre in Derby, central England, last week. PHOTO: AFP

FINANCIAL TIMES - With coronavirus vaccines being administered worldwide, scientists are preparing a new weapon against the disease that has claimed more than 4.5 million lives: an effective antiviral medication to treat the worst symptoms.

While vaccines aim to prevent infection, a pill that speeds up recovery times and could be taken at home would be a significant development, providing treatment for people who are infected and potentially reducing the burden on hospitals.

With autumn under way in the Northern Hemisphere and fears of rising cases in colder months, pharmaceutical companies are locked in a race to achieve a breakthrough.

But there are questions over how much of a difference antiviral treatments can make, and how quickly, to patients with Covid-19, a potentially fatal disease with symptoms including a continuous cough, breathlessness and a high temperature.

How do antiviral drugs work?

The current generation of Covid-19 vaccines focuses on generating antibodies to neutralise the spike protein that the virus uses to enter human cells. With antiviral treatments, scientists must identify how to stop the virus from replicating.

One of the challenges faced by researchers is that antiviral drugs must be able to keep up with the evolving virus.

"They're not vulnerable to a lot of variant changes that you might see with the spike protein," said Dr Nicholas Kartsonis, senior vice-president of clinical research in infectious diseases at US pharmaceutical company Merck. It means that the virus cannot evade antiviral drugs in the way that it can vaccines.

"These sort of antivirals are really targeting the replication process of the virus itself," he added.

Who is working on them?

Merck's tablet, called molnupiravir, would be taken within five days of Covid-19 symptoms emerging, twice a day for five days. It is in phase three trials and the company expects to have data by the end of this year. Merck has also started household trials of molnupiravir in people who do not have the coronavirus but are living with someone who does.

US pharmaceutical group Pfizer is also carrying out late-stage trials of its antiviral tablet. The company is studying two antivirals - a tablet that can be taken at home and an intravenous infusion for patients suffering from more serious disease. The medicines work by blocking the activity of the Covid-19 protease, an enzyme that the virus needs in order to replicate in the body.

An inhaled interferon treatment being produced by a UK drug discovery firm, Synairgen, has also emerged as a potentially promising approach to treating the disease.

Mr Richard Marsden, the company's chief executive, said one of the main ways viruses evade the immune system is "to suppress the production of interferon beta", which plays a significant role in activating the wider immune response and preventing a virus from replicating. "All we're doing is putting this protein, that everyone makes, back into the battleground, and the battleground that matters is in the lungs," he added.

Who would receive antiviral drugs?

Recipients might include immuno-suppressed people for whom Covid-19 vaccines do not work, or a defined group - such as a school, care home or football team - in which they could be used prophylactically to forestall a wider outbreak.

The trick, however, would be the timing, as such products need to be given at the first sign of symptoms, said Mr Steve Bates, chief executive of the UK's BioIndustry Association.

Mr Bates said he would be unsurprised to see at least one antiviral drug ready to be rolled out in the coming weeks, potentially under an "emergency use authorisation", through which products yet to win full regulatory approval can be made available during a public health crisis.

But Mr Bates, a former member of Britain's vaccines task force, suggested mass deployment across the UK population was unlikely. "I think of them as more specialist tools, probably used in particular groups of the population or at a particular point in an outbreak," he added.

People may have to adjust their expectations of how transformative this category of medicines will be.

Efficacy levels might be far lower than the public has come to expect from the vaccines, Mr Bates warned. "Because of this problem of when you administer them, it's almost impossible to get a really good result statistically. And if you get an antiviral that works at 40 per cent, I think that will be brilliant," he said.

However, Dr Eric Topol, director of the California-based Scripps Research Translational Institute, said that provided antivirals were "highly effective and safe, and inexpensive or provided freely, I think they will be quite widely used". This would particularly apply if the treatment was available as "a pill, oral route medication or an inhalation as opposed to an injection under the skin", he added.

What have trials shown?

Although multiple Covid-19 vaccines have been authorised, US group Gilead's infusion remdesivir, which is administered intravenously, is the only antiviral treatment that has been approved by the US Food and Drug Administration (FDA) - despite its uncertain benefit to patients. Scientists at the World Health Organisation say the drug has "no meaningful effect" on mortality or the need for ventilation.

Dr Kartsonis at Merck said antiviral drugs must first be studied, and the correct dose calculated, on healthy individuals before being trialled on Covid-19 patients. That, he said, partly explains why only one antiviral treatment has been approved.

He noted that antivirals must be absorbed, metabolised and excreted correctly, but vaccine makers "don't have to worry about those other characteristics because they don't really apply".

In Europe, Swiss pharmaceutical company Roche is working with Atea Pharmaceuticals on an oral antiviral it believes has dual potential: to treat people with Covid-19 and prevent illness in people who have been exposed to the virus.

Initial results in hospitalised patients with moderate Covid-19 and at high risk of poor outcomes "indicated a rapid and sustained antiviral activity against Sars-CoV-2, with no new or unexpected safety results", the company said.

What role are governments playing?

In June, the United States unveiled plans to invest US$3 billion (S$4.1 billion) in antiviral drug development, saying it would help create the next generation of coronavirus treatments.

The funding will be spent on accelerating clinical trials of antiviral drugs and the creation of a new antiviral drug discovery centre to develop treatments for as yet unidentified coronaviruses in order "to better prepare the nation for future viral threats".

US President Joe Biden's administration also signed a US$1.2 billion deal with Merck in June for 1.7 million courses of molnupiravir if the tablet receives approval from the FDA.

In April, British Prime Minister Boris Johnson established an antivirals task force, modelled on the country's successful vaccines task force.

He pledged "to have at least two effective treatments this year, either in a tablet or capsule form", that could be taken at home following a positive test or exposure to someone with the virus. But there has been no word yet from the task force and its leader, pharmaceutical industry veteran Eddie Gray, on whether that target will be met.

The UK health department said there were "a number of exciting opportunities in the pipeline" and promised to provide "further details in due course".
