Covid-19 antiviral pills show promise, but will they be game changers?

·7-min read

The global battle against Covid-19 may be on the verge of getting a game-changing new weapon: virus-fighting pills. But questions remain on how well these up-and-coming treatments will work in the real world, and what their impact on the pandemic will be.

Hundreds of Covid-19 treatments are currently in development, but in recent weeks major pharmaceutical firms have announced promising results for two oral pills, paving the way for their potential widespread use.

Early this month, a drug from US company Merck became the world’s first oral pill approved for Covid-19 after Britain recommended it for use in people with mild to moderate disease and at least one risk factor for developing severe illness.

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The green light for the drug known as molnupiravir, or Lagevrio – which Merck and its partner Ridgeback Biotherapeutics said reduced the risk of hospitalisation or death for such patients by around 50 per cent – came a day before US company Pfizer released findings for its own pill.

That one, called Paxlovid, reduced the risk of hospitalisation or death by 89 per cent for non-hospitalised high-risk adults with Covid-19, the company said. Detailed or peer-reviewed clinical trial results have yet to be released for either pill – both companies cited interim results.

The two drug makers are seeking authorisation in the United States, with plans to make the drugs available globally subject to national approvals. Countries around the world have already been queuing up for a chance to buy or manufacture the pills.

Britain has recommended the Merck pill for people with mild to moderate disease and at least one risk factor for developing severe illness. Photo: Handout via Reuters
Britain has recommended the Merck pill for people with mild to moderate disease and at least one risk factor for developing severe illness. Photo: Handout via Reuters

Medical experts say the drugs’ impact on the treatment of Covid-19 and countries’ ability to live with the disease could be significant, especially in combination with high vaccination rates. Vaccination is widely considered the best defence against the disease, although experts say other protections like mask wearing and social distancing remain important.

But a lot will depend on how these drugs work in the real world and if their efficacy rates can hold up outside clinical trials, where the drugs were administered to patients early in Covid-19 onset.

“Given that we are likely to be living with Covid-19 in the long term, it will be important to have these types of medications,” said Sanjaya Senanayake, an infectious disease physician and associate professor at the Australian National University Medical School.

“Vaccination is still the best protection against severe cases and hospitalisation, but these medications could really add to our armoury of weapons to fight the virus, and that’s really important,” said Senanayake, who is actively treating Covid-19 patients.

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That could especially be the case for making sure those people who cannot or will not get vaccinated or who experience breakthrough infections do not end up in hospital or die from Covid-19, according to Senanayake.

“For me to know that there are medications out there that can be given to high-risk individuals with Covid-19 before they get to hospital, which prevents them from needing to be hospitalised, makes my life a lot easier too,” he said, pointing to the urgent need to keep hospitals from being overwhelmed with seriously ill patients.

While the Merck and Pfizer pills, if approved around the world, will likely be limited at the start to high-risk groups, as in Britain, there is potential for them to be used more widely and even by people who may have been recently exposed to the virus as a preventive measure, experts say.

“Having an antiviral, particularly an oral antiviral, is going to be a game changer here,” said Ashley Brown, an associate professor at the Institute for Therapeutic Innovation at the University of Florida’s College of Medicine.

“Orally available drugs can be administered to the general population, it’s not like [existing intravenous treatments such as] remdesivir, where you have to go into the hospital and need to meet certain criteria of disease,” she said.

Instead, oral pills could to be distributed early in the disease course or even after an exposure to prevent disease progression or potentially even onward spread of the virus, according to Brown.

It isn’t a question of if the virus will become resistant to the Pfizer compound, likely it’s more a question of when

Alejandro Chavez, Columbia University

However, getting drugs out to infected and exposed people early could depend on a country’s capacity to quickly test and contact trace cases, experts say, and it is not yet clear to what extent effectiveness may decrease if either pill is taken later in a Covid-19 infection.

More data is also needed about the impact of these pills on important elements like disease transmission or on preventing infection if taken following exposure.

Another concern when it comes to antiviral drugs is whether the virus will develop drug resistance. This was a significant struggle in the development of successful treatment regimens for chronic viral conditions like HIV, including for those using a similar mechanism to the one used by Pfizer’s pill.

Experts say it will be important to monitor this and continue to develop new drugs that could be used in coordination with any existing pills to counter resistance.

“It isn’t a question of if the virus will become resistant to the Pfizer compound, likely it’s more a question of when,” said Alejandro Chavez, an assistant professor of pathology and cell biology at Columbia University in New York.

“It is expected that cocktails of drugs similar to how we treat HIV will be what is required to control viral replication and help slow down antiviral resistance,” he said.

Drugs in the same class as the Merck pill molnupiravir have been known to have a higher barrier to drug resistance, according to Brown.

However, one prominent virologist has questioned whether the drug – which works by disrupting the virus’ replication – could inadvertently give rise to more dangerous variants of the virus.

“Molnupiravir could have the unfortunate effect of introducing mutations across every gene and protein of the virus, including the spike, but not necessarily killing it off,” former Harvard Medical School professor William Haseltine wrote in a recent commentary in Forbes.

But other scientists see this as a theoretical risk, which should be monitored but is not likely enough to warrant blocking the use of a life-saving drug. Additional monitoring could also be used to understand if the drug’s mechanism poses any risk for interfering with human DNA, which could mean the drug is not suitable for pregnant women.

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“In my knowledge base, I don’t know of an example of which giving a nucleoside polymerase inhibitor led to the emergence and spread of a more dangerous variant,” said Brown, referring to the class of drugs that includes molnupiravir.

The drug works by inserting mutations into the viral genome to cause enough errors that it can no longer replicate. Even if any mutated strains survived to continue to replicate, the potential for them to be more dangerous was “questionable”, as these would likely be negatively affected, Brown said.

Chavez said while it was difficult to know quantitatively what effects the drug would have on virus evolution in the long term, short-term data show the drug was effective at stopping viral replication.

“The only way to evaluate the long-term risk is through a mixture of laboratory experiments and epidemiologic studies … With any compound applied to human populations there should always be post-approval surveillance,” he said.

Meanwhile, if the drug can help get the pandemic under control, that will cut down on the natural emergence of variants as the virus spreads between people, he said.

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