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Could existing drugs help combat Covid-19? NZ experts weigh in

An anti-malaria drug could be a possible treatment for Covid-19, alongside other existing medicines. Here’s what the experts think.

Several pre-existing drugs are thought to hold potential in the treatment of virus Covid-19. While research is ongoing into new treatments and vaccines, if anything currently available is found to be effective it could be distributed to those affected much more quickly, due to existing stockpiles and having already been through human trials.

Below, the Science Media Centre has corralled to two experts from the University of Otago to assess how promising these treatments are, and a University of Auckland scientist provides insight into a clinical trial set to get under way in New Zealand.

Dr Mark Thomas, associate professor in clinical molecular medicine & pathology, School of Medical Sciences, University of Auckland

Auckland City Hospital is one of a number of hospitals in New Zealand and Australia hoping to recruit patients into two clinical studies which will help to determine whether either an anti-malaria medicine or an anti-HIV medicine will help patients with Covid-19 to recover.

Patients admitted to hospital, either in a medical ward if their illness is not severe, or an intensive care department if their illness is severe, will be offered the opportunity to participate in the studies.

If patients or their family provide consent, they will be randomly allocated to treatment with hydroxychloroquine (an anti-malaria medicine), or with Kaletra (an anti-HIV medicine), or with a combination of both hydroxychloroquine and Kaletra, or with a placebo.

Neither the patients, nor their family, nor the medical team caring for the patients, will know which of the four possible treatments the patients are receiving. It is what is called a double-blind study, which allows the effects, potentially beneficial, or harmful, to be evaluated without any bias affecting the evaluation of the effect of each treatment on patients’ outcomes.

This clinical trial will help us understand whether these drugs are effective therapies for Covid-19.

It is very unlikely that patients who are not participating in these studies will be offered these medicines because their medical teams will not know, until this and other similar trials are completed, whether the medicines are helpful, harmful or have no discernible benefit or harm.

Dr Christopher Gale, senior lecturer at the Department of Psychological Medicine, University of Otago

There are a fair number of “cures” for Covid-19 being mentioned in social media and by various public figures. This is normal human behaviour: people will try to do whatever they can to stay well and be able to care for their families and friends. However, there is very little data behind these claims.​

There have been case reports from China and Italy of people in intensive care who have been treated with various antiviral and antibiotic medications, but no clear indication that any of these helped.

What is happening is that various antiviral medications are being tested rapidly in the severe cases. It will not take much time (or participants in the trials) to see if such a medication works or does not. Some will be shown to work, some will not. At that point the health system will be able to offer treatments for Covid-19 with confidence. The regulations and ethical approval for such trials are being facilitated by many governments.

At present, however, we have no data. There is no point in seeking this medication or that – the medications we have available in New Zealand are for other conditions and are needed for those people. If and when we have treatments that work, we will have to consider how we source them – which may include deliberately going off-patent and getting pharmaceutical companies in New Zealand to make them.

Professor Kurt Krause, Department of Biochemistry, University of Otago

At present scientists are seeking direct-acting antiviral drugs that target coronavirus in the hope that these drugs might serve as a bridge until a vaccine is developed. Since both drug and vaccine development take such a long time, interest has arisen in already approved drugs that can be repurposed to target Covid-19. To date, these repurposed drugs fall into three main groups: polymerase inhibitors, protease inhibitors, and other.

Polymerase inhibitors include some of the most promising options, and the notable members of this group are remdesivir, galidesivir, and favipiravir. They work by blocking the enzyme that allows the virus to replicate its nucleic acid coding strand. If a virus cannot replicate its nucleic acid, it cannot replicate at all.

Remdesivir is approved for use in animals against diseases like FIP (Feline Infectious Peritonitis); it’s being evaluated in a small clinical trail in China and results are due next month. Favipiravir was developed in Japan and has shown early promising results, but nothing has been published in the peer reviewed literature yet. Galidesivir is a polymerase inhibitor that was partly developed in NZ and has activity against coronavirus-19. It is being considered now for further studies and is notable for its strong NZ connection.

Protease inhibitors are a major drug class in use against HIV. For HIV they work by blocking an enzyme that processes proteins that the virus needs for growth. During the Sars epidemic it was discovered that Kaletra (lopinavir/ritonavir), a common anti-HIV drug, seemed to help coronavirus-infected patients. Early data on its use for coronavirus infection suggests weak to no activity, but it was an early study with small patient numbers.

Another repurposed drug being studied is camostat mesylate. Like Kaletra it is a protease inhibitor but apart from that they are very different. Camostat meslyate inhibits a completely different protease that is used by coronavirus to mediate its uptake into cells. The good news that is that camostat is already used in people but for a non-infectious condition, chronic pancreatitis, but the cautionary note is that camostat has not yet been used in people for coronavirus treatment.

The final drug in this repurposed grouping is in the “other” category. It is called chloroquine. Chloroquine is an antimalarial drug, long in use, especially in travel medicine. It turns out that it inhibits SARS2-CoV replication in the test tube and it has garnered wide attention because of it. Physicians are keen to learn if this observation could be translated into success in living humans. A cautionary note is that chloroquine has been looked at before with other viruses and has not been found to be effective.

Although many of these compounds can, and are, being given now in an off-label fashion, the best way to use them is in a randomised controlled trial (RCT). That’s because RCTs allow us to learn quickly if a drug actually works or not. RCTs have been essential in other viral epidemics and pandemics, like HIV, to allow scientists to learn the most effective way of treating infections. RCT evaluation of these candidates would be the best way to sort their utility in treating Covid-19 infection.

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