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As New Zealand prepares to open its borders, Professor Kurt Krause takes stock of the Covid-19 medications we already have – and those that are on the way
Covid-19 Response Minister Chris Hipkins was quoted in November saying New Zealand needs to be prepared for the spread of the virus throughout the country in the coming weeks.
Although an unsettling thought, it is a good time for a stocktake of the medications available in New Zealand to treat Covid-19, including anti-inflammatories, monoclonal antibodies, and the new anti-Covid pills.
Monoclonal antibody treatments
Monoclonal antibodies are an important addition to the anti-Covid treatment regimen. First marketed by Regeneron, but now distributed overseas as Ronapreve by Roche pharmaceuticals, this therapy is a highly purified antibody protein directed against the spike protein of SARS-CoV-2.
Many people first heard of this therapy when they saw that former US President Donald Trump was a recipient after he contracted Covid-19. Multiple drug companies have now developed similar versions of anti-Covid monoclonal antibodies and to date, all seem both safe and effective.
In fact, when administered early during infection, usually within the first four to seven days, these monoclonal antibody treatments are about 80 percent effective at preventing hospitalisation or death.
This treatment is recommended by the World Health Organization for people over 65 with co-morbidities, like diabetes, or who are immunocompromised. It’s a one-time treatment that must be given intravenously or subcutaneously, which does limit its ease of use. Hospitalised patients don’t benefit as much unless they are lacking a Covid-19 antibody response.
The administration of these antibodies can, in some cases, also prevent infection. This use could be important for high-risk patients exposed in nursing homes and hospital wards.
New Zealand has entered into an agreement with Roche to purchase Ronapreve once it is approved by Medsafe. A transparent and equitable plan for its rollout and usage is needed.
Anti-Covid pill treatments
Two new promising pill-based therapies have posted encouraging results in the past few months, but neither is currently approved.
The first agent, molnupiravir, was developed by Merck pharmaceuticals. It is a pill designed to be given twice a day for five days, early in the course of infection.
In non-hospitalised at-risk adult patients with mild to moderate Covid-19, it was found to be 30 percent effective at preventing hospitalisation or death. The mortality benefit, however, was much greater. Molnupiravir works by interfering with effective viral replication.
In studies to date it was well tolerated. Some concerns about the potential for mutagenesis have been raised for molnupiravir although Merck has data suggesting no significant patient risk exists.
This medicine targets the same population who would benefit from monoclonal antibodies, but with the advantage of being taken in a pill form (no IVs or needles required). Pharmac has an agreement in place with Merck reportedly to purchase 60,000 doses of molnupiravir.
The second oral anti-Covid agent of note is paxlovid. It is a combination of the Pfizer drug PF-07321332 and ritonavir. It interferes with viral replication by blocking the function of a key viral protein called Mpro.
Like molnupiravir, it is given as a pill orally for a five-day treatment course. A recent press release from Pfizer reported a study in which high-risk non-hospitalised adult patients treated within three days of showing symptoms had an 89 percent reduction in hospitalisation or death. Paxlovid is not yet approved for use outside of clinical trials.
It may be some time before New Zealanders have access to either of these two treatments. Neither of the two studies discussed above has been published or peer reviewed.
Full information about side effects and risk profiles for both drugs should be released. Medsafe must complete its review of both medications and a clear plan for their rollout and usage on both islands will be needed.
While this will likely take some time, both of these drugs look promising and both could be lifesaving for at-risk New Zealanders.
In-hospital treatments
With all the buzz about the new pill treatments for Covid-19, it’s easy to forget that a number of treatments are already available for hospitalised Covid-19 patients.
Many physicians now think of Covid-19 as having two main stages. In the early stage the virus is the villain and therapies are anti-viral focused.
In the next stage, the patient’s immune system becomes the villain and overreacts to the infection causing collateral damage that can be severe. In this stage, patients are usually on oxygen and some require mechanical ventilation while their lungs clear the virus and heal the severe, damaging inflammation.
For treating the inflammation found at this stage of Covid-19 infection, three anti-inflammatory effects agents have been pressed into use – dexamethasone, tocilizumab and baricitinab.
Dexamethasone is a powerful anti-inflammatory steroid that has been around for decades. Large studies involving dexamethasone have found it to lower mortality in severely ill Covid-19 patients by 30 to 40 percent.
Tocilizumab is a monoclonal antibody that binds to a cell surface protein, interleukin 6 receptor (IL-6R), and blocks its function, while baricitinab inhibits janus kinase, a protein found in the JAK-STAT system.
Both IL-6R and JAK-STAT have been shown to directly stir up damaging inflammation in severe Covid-19 infections. Studies conducted on tocilizumab and baricitinab, which are generally used in patients already on steroids, usually report an additional 15 to 30 percent drop in mortality from that obtained from steroids. These drugs are available in New Zealand, but there is a global shortage of tocilizumab, and baricitinab is not yet approved.
Finally, remdesivir is available in New Zealand for use in hospitalised patients with moderate to severe Covid-19 infection. It is an intravenous medication that interferes with viral replication, a bit like molnupiravir.
Unfortunately, it has only been found to be mildly effective in this group of patients. However, recent work released at an international scientific meeting found it 87 percent effective in preventing hospitalisation or death when used early in infection. It’s looking like this medication needs to be shifted to early use to get the most benefit.
New Zealand has made good progress in lining up Covid-19 treatments, but there is much more to do.
Corticosteroids, like dexamethasone, are in wide use and tocilizumab and baricitinab are now available. Monoclonal antibody therapies are coming into place and once available will be important, potentially lifesaving therapy.
Two promising pill-based treatments, molnupiravir and paxlovid, appear to be heading for approval and will likely be as effective as monoclonal antibodies, but easier to take. Remdesivir is also a therapeutic choice but may be better used earlier in infection.
Having the best anti-Covid-19 therapies in place as our Covid-19 numbers increase would be a great way for New Zealand to prepare for opening up its border.
Professor Kurt Krause is a principal investigator in the Maurice Wilkins Centre of Research Excellence and was the inaugural Director of the Webster Centre for Infectious Diseases. He declares no conflicts of interest
