Covid-19: The antivirals are coming. How do they work?

New oral drugs shown to greatly slash the risk of severe sickness or death from Covid-19 are soon to be available to vulnerable Kiwis who need them. What are antivirals? Science reporter Jamie Morton explains.

What are Covid-19 antivirals?

They’re not an ambulance at the top of the cliff – that’s why we have booster shots and other health precautions – but rather parachutes for a safer landing.

Covid-19 antivirals like Pfizer’s Paxlovid pills have the potential to greatly slash the number of patients who get severely sick or die from the virus.

One top Yale University infectious diseases expert called the drug, soon to be available in New Zealand, “the beginning of a game-changer”.

Paxlovid, the world’s first oral treatment of its type, contains two existing “protease inhibitors” – Nirmatrelvir and Ritonavir – which work together to effectively block the Sars-CoV-2 virus that causes Covid-19.

Nirmatrelvir works by binding to the virus and inhibiting a key enzyme, called the main protease, which it uses as one of its first steps in the replication process.

While Ritonavir doesn’t work directly against Sars-CoV-2 – it’s better known as a treatment against HIV/AIDS – it helps slow the breakdown of its fellow inhibitor, allowing Nirmatrelvir to remain active in the body stronger and for longer.

“What this does, is it prevents the virus multiplying, keeps virus levels low, and allows your body to overcome the infection,” said Dr Krishan Thiru, Pfizer’s Australia and New Zealand medical director.

How effective are they?

Clinical trials have shown Paxlovid to work impressively.

In a study carried out among people with risk factors like age and underlying medical conditions last year, it was demonstrated that, if given within five days of diagnosis, Paxlovid slashed the risk of hospitalisation and death by about 90 per cent.

Common side effects, usually mild, include an impaired sense of taste, diarrhoea, increased blood pressure and muscle aches.

Another antiviral which New Zealand signed up for last year through pre-purchase agreement – Merck Sharp and Dohme’s Molnupiravir (brand name Lagevrio) – doesn’t appear to be perform as well, with data reviewed by the US Food and Drug Administration showing it was only about 30 per cent effective at cutting the risk of hospitalisation.

Thiru said that, while Paxlovid has already been approved for use in around 40 countries, there still wasn’t enough data to show how it was working in “real world” settings.

“But what we can say is that, if what was seen in the clinical study is replicated in the real world in New Zealand, it really does have the potential to significantly improve Covid-19 outcomes, and reduce some of the burden on healthcare workers,” he said.

“In this current wave, we’ve seen up to 1000 people in New Zealand hospitals, with dozens of people in ICU and sadly, an average of 10 people losing their lives every day.”

Do they work as well against Omicron?

Recent data suggests the active ingredients in Paxlovid and Lagevrio held up against the Omicron BA.1 subtype as well as against the original strain of the virus.

Thiru noted that Paxlovid worked by blocking an enzyme within the virus, rather than targeting a spike protein on the outside of the virus, as vaccines do.

While mutations within the spike protein had led to immunity-evading variants like Omicron, the specific enzyme inside the virus tended to be fairly consistent across all its forms.

“That’s why we believe it will work amongst different variants – and we do have some laboratory data showing that it does retain potent antiviral activity against Omicron,” Thiru said.

How and when will they be dispensed?

Importantly, antivirals aren’t the same thing as a vaccine: and drugs like Paxlovid are intended to be prescribed to at-risk people after they’ve already tested positive with Covid-19.

“It’s a five-day course of tablets – morning and evening – for vulnerable patients who’ve just been diagnosed, but are at risk of progressing to severe disease.”

The Government has pre-purchased 60,000 courses of Paxlovid and Lagevrio, with MedSafe already having given provisional approval for the former to be used in New Zealand.

Critics have accused Pharmac over delays of getting Paxlovid here, but the drug-buying agency has cited high demand for the hold-up. The first shipments are expected to be announced soon.

It’s also unclear just how the drugs will be administered and targeted.

Thiru said Paxlovid was being supplied to New Zealand as a prescription-only medicine, and it would be up to the Government to determine the precise eligibility criteria for it.

In the US, people who test positive at pharmacies can get it for free.

What are the drawbacks?

Dr Colin McArthur, an intensive care specialist at Auckland City Hospital, said an obvious challenge would be how to get the pills to people in time.

“They need to be taken within five days from the beginning of symptoms, which some people may not recognise, and not see a need to be tested,” he said.

“So there’s going to be a need for communication to patients who are at higher risk to know there’s a treatment that could be available.”

McArthur also expected challenges around ensuring the roll-out would be equitable – and that people right across the country and health sector could access them.

Overall, though, he said the new antivirals could make a major difference here.

“I look forward to having them available here. We now have multiple tools in the toolbox to help the country manage, and this is a new one that could be really important.”

What other Covid-19 treatments are out there?

Clinicians here already had access to the intravenous antiviral drug remdesivir, which has been used for patients hospitalised within the first seven days of illness.

“It is also effective at reducing the risk of hospitalisation in those at high risk, but early administration of an intravenous drug outside of hospital is difficult,” McArthur said.

“Processes are being established now to provide this treatment in the community for those at the greatest risk of deterioration, as supplies are limited.”

Another treatment aimed at the virus are monoclonal antibodies, which help the body identify and eliminate the virus.

“We have supplies of Ronapreve – a combination of casirivimab and imdevimab – in New Zealand currently, but unfortunately although this is effective against earlier variants such as Delta, it is not active against Omicron,” he said.

“Some monoclonal antibodies such as sotrovimab do retain activity against Omicron, but these are understandably in high demand globally and are not yet available here.

“These treatments are also given by injection and their use pre-hospital where they are most effective has similar challenges to remdesivir.”

Source: Read Full Article