Trial shows muted impact of Paxlovid on healthier patients

More data has been issued by pharmaceutical giant Pfizer about the efficacy of its COVID-19 oral antiviral treatment, one of two that are currently available on the Pharmaceutical Benefits Scheme (PBS).
 
This week the company reported that it would not add any new patients from the broader population to a clinical trial of its nirmatrelvir plus ritonavir (sold as Paxlovid) treatment, after the study did not show statistically significant reductions on hospitalisation and mortality.
 
It is a result Bloomberg described as ‘major setback’ for the likelihood of administering the treatment more widely than the high-risk groups to whom it is currently targeted.
 
The Pfizer announcement made on Tuesday included the results of an analysis of 1153 patients enrolled in the company’s ‘EPIC-HR’ study.
 
Those taking part had a confirmed diagnosis of COVID-19 whose symptoms had begun within five days. They were either fully vaccinated with one risk factor or underlying medical condition linked to the likelihood of developing severe illness or were unvaccinated with no risk factors.
 
The company said the relative risk reduction of hospitalisation and death stood at 51%, with five instances among those treated with the oral antiviral and 10 among the placebo arm. However, the results were deemed ‘non-significant’.
 
It also reported the results of 721 vaccinated adults with at least one risk factor for severe illness as having a 57% relative risk reduction in hospitalisation or death.
 
However, given the low numbers (three out of 361 patients in the treatment arm were affected, compared to seven out of 360 in the placebo group), the results were again described as statistically ‘non-significant’.
 
Pfizer said they would nevertheless be included with a new drug application with the US Food and Drugs Administration (FDA) for the drug’s full approval among high-risk patients but confirmed the trial would cease among standard risk people.
 
‘The company will focus efforts on generating further data on [Paxlovid] in vulnerable populations, including longer treatment durations in immunocompromised individuals, as well as exploring other clinical development opportunities, such as its potential use in hospitalised patients with severe disease,’ the company stated.
 
The results point towards a situation where people who are vaccinated and without additional risk factors are unlikely to gain much benefit from the treatment.
 
It had previously been speculated that the oral antivirals could be used among the whole population when the treatment is in wider supply.
 
In the past month, the first real-world assessments of the oral antiviral drugs that are currently provisionally approved in Australia have emerged.
 
Again, while they showed cautiously encouraging results for high-risk patients, there was limited impact for the rest of the population.
 
A study that took place in Hong Kong included details on the efficacy of both molnupiravir (sold as Lagevrio) and nirmatrelvir plus ritonavir in hospitalised patients.
 
The study took place during the Omicron wave at the start of the year, while the original clinical trials had taken place during the Delta wave.
 
The authors concluded the treatment worked best among the ‘elderly with multiple pre-existing comorbidities and who had not been fully vaccinated’.
 
They also advocated for ‘the prioritisation of nirmatrelvir and ritonavir over molnupiravir use in COVID-19 patients whenever accessible and clinically appropriate, in view of the former’s substantial mortality benefit’.
 
The results of the Pfizer trial also appear to correlate with data emerging from Israel, with a recent preprint reporting ‘no significant benefit’ in preventing severe COVID-19 among younger adults aged 40–64.
 
However, it found hospitalisations and deaths were widely prevented among older patients, reporting a 67% reduction in hospitalisations and 81% reduction in mortality among those treated.
 
Who is eligible in Australia?
According to PBS criteria, the drugs can be prescribed for those with mild-to-moderate COVID-19 confirmed by a PCR or rapid antigen test within five days of symptom onset, among the following patient groups:

• Those aged 65 or older, with two other risk factors for severe disease
• Those aged 75 or older with one other risk factor
• Those aged 50 and older who are of Aboriginal or Torres Strait Islander origin with two further risk factors for severe disease
• Those with moderate-to-severe immunocompromise

COVID-19 molnupiravir Paxlovid Pfizer