Molnupiravir to be used only as a last resort: Taskforce

The oral antiviral drug most widely dispensed to treat vulnerable patients with COVID-19 should not be routinely used, the National COVID-19 Clinical Evidence Taskforce has advised.
 
The group updated its listing for molnupiravir (sold as Lagevrio) on Friday, after considering data from the large-scale PANORAMIC trial in the UK, which compared the impact of the treatment to standard care.
 
That analysis, which was published in October, looked at data from 25,000 patients, most of whom were older than 50. The randomised trial also included a group aged 18 and above with co-morbidities that increased their risk of severe illness.
 
Its researchers concluded that molnupiravir did not reduce hospitalisations or deaths among higher risk, vaccinated adults with COVID-19, even thought it did seem to prompt a faster recovery time, as well as reduced viral load.

As a result, the Taskforce said the trial results mean there is now ‘high certainty evidence’ that the treatment does not have an impact on hospitalisation or death in ‘multiply-vaccinated adults with mild COVID-19 and one or more risk factors for disease progression’.
 
It also said the trial underlines its existing stance towards nirmaltrelvir plus ritonavir (sold as Paxlovid) and remdesivir as the preferred antiviral treatments for mild COVID.
 
Professor Mark Morgan, the Chair of RACGP Expert Committee – Quality Care (REC–QC) and a member of the Taskforce’s guidelines leadership group, stressed the importance of using the most effective treatments and noted the implications of the PANORAMIC study.
 
‘In summary, molnupiravir did not work,’ he told newsGP.
 
‘The drug is an antiviral and seems to reduce viral load but that did not translate into saving people from severe disease.
 
‘I hope patients don’t miss out on effective treatments because of ongoing use of less effective treatments.’

The authors of the Taskforce rationale acknowledge evidence is less certain about the impact of molnupiravir in high-risk patients, including those with severe immunosuppression, and in residential aged care facilities.
 
They also noted that the full picture in similar high-risk settings remains unclear for other treatments, including nirmatrelvir plus ritonavir.
 
‘Current evidence provides greater certainty of clinical benefit for other antiviral agents in the broader population; therefore use of these other antivirals agents rather than molnupiravir is preferred,’ they wrote.
 
‘However, there may be specific circumstances for the highest risk patients, where all other treatment options are contraindicated or inappropriate, in which non-routine use of molnupiravir might be considered, in consultation with specialist clinicians where necessary.’

According to the most recent Department of Health and Aged Care (DoH) COVID-19 update, molnupiravir has been prescribed at more than three times the rate of nirmatrelvir and ritonavir overall, with 329,050 prescriptions dispensed compared to 96,020 as of 2 December.
 
While the latter is regarded as the most effective treatment, it also has a significant number of interactions with other drugs that make it substantially more complex to prescribe.
 
Because of this, Dr Anthony Marinucci, Chair of RACGP Specific Interests Aged Care, told newsGP the use of oral antivirals in this setting remains a ‘complicated issue’.
 
‘The PANORAMIC trial was carried out in a different population with a slightly different treatment model – eg specialist clinics for high risk individuals – so one must take care when extrapolating recommendations to a different cohort of patients – ie Australia,’ he said.
 
‘Compounding this, as mentioned in the communique, there is less evidence about the effect of molnupiravir in the highest risk patients and in residential aged care.
 
‘After careful consideration of the risks versus benefits, a shared decision-making process will be made to prescribe or not.’
 
Nonethelss, Dr Nick Simpson, a DoH medical advisor, noted an uplift in recent rates of nirmatrelvir and ritonavir use in the recent COVID-19 Primary Care Update webinar, with recent prescriptions rising to around 30% of the total for COVID-19 oral antivirals.
 
‘Perhaps people are getting more familiar with Paxlovid and when they can cease concomitant medicines that might be causing those problematic drug interactions, so it is encouraging that it is being used slightly more frequently than before,’ he said.
 
Both treatments were added to the PBS earlier this year, with GPs able to access molnupiravir from March and nirmatrelvir and ritonavir from May.
 
The Taskforce also referenced observational studies, including one from the Victorian Department of Health that concludes molnupiravir significantly reduces the risk of hospitalisation and death.

‘The nature of these studies means that their results are open to significant bias – particularly selection bias – and substantial confounding – both the healthy user effect and confounding by indication – and cannot provide reliable evidence to determine the effectiveness, or otherwise, of molnupiravir,’ the Taskforce concluded.
 
‘However, these studies are very helpful in generating hypotheses, particularly about groups most likely to benefit from treatment, for testing in future randomised controlled trials.’
 
Professor Morgan notes that other countries have also changed their advice on molnupiravir, including the UK, where it is no longer recommended for use by the country’s National Institute for Health and Care Excellence.
 
He also said that vaccine boosters should be the mainstay of preventing serious disease.
 
Meanwhile, the Pharmaceutical Benefits Advisory Committee (PBAC) recently recommended expanding eligibility for both oral antiviral treatments to include those previously hospitalised with COVID-19.
 
Dr Simpson said the change would be relevant in the example of a young patient who may otherwise be fit but had a bad experience with COVID.
 
PBAC also recommended expanding eligibility to patients who have received anti-CD20 monoclonal antibody treatment in the past 12 months, as well as softening the requirement for a verified COVID-19 test result.
 
The recommendations are expected to be introduced early next year.
 
The Taskforce has published a prescribing guide for nirmaltrelvir plus ritonavir (Paxlovid) on its website.

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