Today is a big step forward in our battle with this virus. While we have been extremely fortunate to have safe and effective vaccines, which will remain the backbone of our strategy moving forward, and we have already been using antibody and antiviral therapy we can give intravenously, the addition of safe and effective antivirals that can be given orally, in my opinion, will make an enormous difference.

Given these antiviral medications are administered orally, they can be used more in the community setting and have been shown to work well particularly at reducing the risk of going to hospital and progressing to more severe disease in people who are high risk of doing so when infected with the SARS-CoV-2 virus. Both medications have been shown to be safe and effective in large clinical trials and both are given as a 5 day course.

While both are antivirals, there are some subtle differences in how they work and in exactly who they are best for particularly given one of them can have significant interactions with many other medicines. In many ways, in my opinion, the availability of effective oral medications to treat this virus has been perhaps the missing piece of the puzzle in our efforts to optimise our tools to manage this pandemic.

Paxlovid is an important new treatment for COVID patients as it targets a unique process in COVID replication that does not related to the spike protein (the target for most other COVID treatments and vaccines). This means that Paxlovid is less likely to lose efficacy due to mutations in the spike protein, which to date have been associated with the major variants (including Delta and Omicron). 

Paxlovid is however an expensive medicine and one that the Australian Healthcare system cannot afford to supply to all Australians. Currently a disproportionate number of patients being treated for COVID with monoclonal antibodies in the community, being admitted to hospital, and requiring ICU beds are unvaccinated. The expense of supplying Paxlovid to these Australians will place a further burden on an already overstretched healthcare system.

While Paxlovid is another valuable asset in the fight against COVID, vaccination remains our most important and cost effective means of fighting the pandemic.

This is such a fantastic advancement and opportunity for effective treatments, designed and tested to specifically target SARS-CoV-2, that can be easily accessed as oral, take-home formulations.
 
Molnupiravir targets the machinery that replicates the viral genome, while Paxlovid targets the viral protease that is essential for infectivity and is formulated with ritonavir, which ‘boosts’ the therapeutic levels of the active drug.
 
These drugs are best prescribed to people who have contracted SARS-CoV-2 and are at high risk of developing severe COVID-19, or may have an underlying condition that may have reduced their vaccine responses.
 
These agents are not a replacement for vaccination. There may initially be limited supply, but the availability of these new drugs bodes well for offering clinicians treatment choices for those most at risk. Of note, these drugs work very well in the initial viral phase of illness - the first few days, but will be of no benefit for patients already critically ill in hospital or on a ventilator.

The TGA has approved the Novavax vaccine and two oral pills for use in Australia. The antiviral treatments, Lagevrio (Merck) and Paxlovid (Pfizer) have also been approved by the TGA. They are prescription only and not a substitute for vaccines but are effective in treating people with mild to moderate COVID-19, who have a high risk of progressing to severe disease.

Lagevrio (Molnupiravir) is most effective when taken during the early stages of infection and is recommended for use as soon as possible following a positive COVID-19 test and within five days of symptoms onset. Pfizer’s Paxlovid tablets are packaged for oral use for the treatment of mild-to-moderate coronavirus disease (COVID-19) in adults with positive results of direct SARS-CoV-2 testing, and who are at high risk for progression to severe COVID-19, including hospitalisation or death. The risk factors include obesity, older age (>60 years), diabetes mellitus, or heart disease.

Availability of these two antivirals in Australia for the treatment of COVID-19 infections is an important development in bringing this pandemic under control. Both drugs have cross-strain activity against COVID-19 and complement available vaccines.

They offer a treatment for cases which have not responded adequately to vaccination or for which vaccination is contraindicated. Like the antivirals, Relenza and Tamiflu for influenza, they provide physicians with effective treatments when presented with patients suffering from serious COVID-19 infections.