Health officials flag increased use of antivirals as COVID becomes endemic

What is being done to raise the public profile of the two new COVID-19 oral antivirals? How much do we really know about the difference they are making?
 
What more can be done to ensure they reach the right people at the right time? And what is their long-term role in addressing COVID-19 as the virus becomes more endemic?
 
These are the questions, among many others, that primary care health professionals involved in the COVID-19 response have been asking in recent weeks.
 
But while much still remains unknown, one thing is clear; the role of the two oral antivirals approved for use in Australia – molnupiravir (sold as Lagevrio) and nirmatrelvir plus ritonavir (sold as Paxlovid) – is likely to expand further in the next few months.
 
Both have now been approved for listing on the Pharmaceutical Benefits Scheme (PBS): molnupiravir can already be issued by general practice, while GPs will be able to prescribe the nirmatrelvir plus ritonavir treatment on the PBS from the start of May.
 
The additions have come at the same time as clinicians have noted an apparent decrease in efficacy in sotrovimab against the current dominant subvariant of SARS-CoV-2, which is only likely to increase the focus on the two new oral treatments.
 
Until recently, the monoclonal antibody, which is administered intravenously, had been one of the most widely used treatments to reduce the risk of severe COVID-19 in vulnerable patients.
 
However, according to the National COVID-19 Clinical Evidence Taskforce, it is now only recommended for use when the Omicron BA.2 subvariant is suspected when ‘other treatments are unsuitable or unavailable’.
 
Professor Brendan Murphy, Secretary of the Department of Health (DoH), articulated a shift in dynamic in the COVID response in the ‘COVID-19 Treatments Forum’ webinar last week, as official policy transitions to one of harm minimisation.
 
‘Whilst vaccination remains a crucial part of that approach, and we can’t neglect to keep pushing those additional doses that are required, the role of treatments is now of increasing importance,’ he said.
 
‘The oral treatments … are going to have [an] important and an increasing role over the coming 12 months.’
 
But while transmission is still predominantly among younger people, Professor Murphy stated the focus for the antivirals’ use will remain on older people and those with underlying disease.
 
‘These are the people we need to get these treatments to early enough in the course of their infection to be effective,’ he said. ‘We believe we bought enough to meet the needs of clinically indicated populations.’
 
Increased use
Between them, the projected supply of oral antivirals currently stands at enough to treat well over one million people with COVID-19.
 
The Federal Government confirmed 300,000 courses of molnupiravir last year, while a million nirmatrelvir plus ritonavir treatments have also now been ordered – although molnupiravir currently remains the most accessible and available.
 
The target groups are those aged 65 years and over – or 50 and over among Aboriginal or Torres Strait Islander patients – with two or more risk factors for severe disease, as well as those aged 75 and older with one risk factor. All patients with moderate-to-severe immunocompromise aged over 18 are also included.
 
And while the drugs may not yet have broad recognition in the wider public, their use is increasing, with Deputy Chief Medical Officer Professor Michael Kidd reporting ‘a big pick-up’ in PBS molnupiravir prescriptions recently.
 
Of the 5386 prescriptions reported last week, most had been within the past few days, with the majority issued by GPs.
 
On Saturday 9 April, the DoH reported 42,867 courses of the oral antiviral had been issued so far via the National Medical Stockpile, which GPs will need to continue using until the PBS listing goes live next month.
 
Barriers to use
GPs are, however, reporting difficulties prescribing the treatments in a timely way.
 
The oral antivirals are considered most effective if taken within five days of a patient’s diagnosis or of symptoms developing. For the GP Dr Chris Moy, that is a challenging timeline to adhere to, particularly with the current volume of cases.
 
‘The problem is trying to join the dots in time,’ he told the COVID-19 Treatments Forum.
 
‘Unfortunately, we are not getting a very high hit rate at the moment – I’d be surprised if it is more than 30 or 40%.’
 
He said over-complex guidelines and inconsistency between the approaches in different states as other potential barriers that could be limiting the use of the antivirals.


The use of COVID oral antivirals may not be limited to people with co-morbidities as supplies increase later in the year. (Image: AAP)

Meanwhile, Professor Kidd urged health professionals to be aware of the long list of people categorised as immunocompromised.
 
‘It is very important that people familiarise themselves with the people on that list,’ he told those watching the COVID-19 treatments webinar, highlighting the broad range of conditions included, from people with HIV/AIDS to those with intellectual and physical disabilities.
 
‘Please make sure you are aware of who is on that list. Because many of your patients may be eligible for molnupiravir prescribing on the PBS if they are aged 18 and above.’
 
The drug interactions are particularly complex with Paxlovid, with reports of prescriptions taking up to 90 minutes in hospital settings. However, both Dr Moy and Professor Kidd said GPs are ideally positioned to navigate contraindications given their knowledge of their patients and their treatments.
 
Australia’s Chief Medical Officer Professor Paul Kelly also acknowledged that the profile of the antivirals needs to be raised among the broader community.
 
‘We need to do more work in that area and we are doing it,’ he said.
 
He stated his support for widespread pre-screening so that vulnerable people who contract COVID-19 can seamlessly receive appropriate treatment.
 
‘I have this vision that anyone who is in one of those high-risk groups has a treatment plan before they get COVID, not after they get COVID,’ Professor Kelly said.
 
The clinical evidence so far
Head of the Therapeutic Goods Administration (TGA) Adjunct Professor John Skerritt reiterated that there is not yet conclusive evidence on the relative efficacy of the antiviral treatments, pointing out that clinical trials took place in very separate conditions.
 
‘They have been tested against different circulating strains, different disease pressures, different hospitalisation criteria and different patient inclusion criteria,’ he said. ‘I do not believe there is a valid back-to-back comparison of the two treatments.’
 
Professor Skerritt also highlighted practical constraints in assessing the real-world effectiveness of the treatments, although he believes evidence will emerge in roughly the same timeframe it took for detailed data on vaccine efficacy to come out.
 
He also thinks the treatments are likely to become more widely used among the broader population.
 
‘With endemic COVID, we could well see ourselves in a position where these drugs are very widely available in six or 12 months’ time and we don’t need to limit to people with co-morbidities,’ he said.
 
‘If the drug prevents the progression of disease in someone with co-morbidities, it would be hard to imagine that it wouldn’t also prevent viral replication in someone who doesn’t have co-morbidities.’
 
The RACGP has produced a list of COVID-19 resources with information relevant for every state and territory.
 
A guide featuring information GPs need to know about the oral antivirals has also been published by newsGP. 
 
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antivirals COVID-19 Lagevrio molnupiravir nirmatrelvir plus ritonavir Paxlovid