Five new drugs are to be trialled in 30 hospitals across the country in the race to find a treatment for Covid-19, it has emerged. Just days after World Health Organization trials of hydroxychloroquine, the drug promoted by Donald Trump as a cure, were halted, British scientists are looking to sign up hundreds of patients for trials of medicines they hope will prevent people becoming ill enough to need intensive care or ventilators.
They range from drugs such as heparin, which is used for blood thinning, to therapies still in clinical trial for conditions such as muscular, lung and blood disorders, which have evidence of potent anti-viral or anti-inflammatory properties.
The studies are part of the Accord (accelerating Covid-19 research and development) programme involving doctors and scientists, industry, the NHS the National Institute for Health Research (NIHR) and UK Research and Innovation.
“We are looking for a signal of both safety and efficacy, something that could reduce the severity of the disease, shorten its duration and prevent patients going into the intensive care environment,” said Prof Tom Wilkinson, a respiratory medicine consultant, who is the Accord academic lead, from the NIHR Southampton Biomedical Research Centre.
Just a handful of patients have enrolled for the trial so far and with coronavirus patient numbers falling, researchers are keen to quickly enlist as many as possible, said Wilkinson.
“These are small, rapidly deliverable studies if we get patients in so we’re looking only to achieve around 60 patients for each arm of the trial to receive one of the drugs compared to usual standard of care,” he added.
Hospitals including St Thomas’ – where Boris Johnson was treated – and Guy’s in London, and major hospitals in Liverpool, Manchester, Leeds, Leicester and Glasgow are also participating, as are Southend and other coastal hospitals where fears of new clusters have emerged after crowded beach scenes last weekend.
The five drugs, which can be disclosed for the first time, are:
Heparin, a blood-thinning drug used in hospitals up and down the country. It will be given to Covid-19 patients for the first time next month. In a number of conditions it has been shown that if it is nebulised rather than injected, it can “have a dramatic effect in the lung”, said Wilkinson.
“It is a big sticky molecule which can attach to viruses and stop them from entering cells and secondly it may have an important anti-inflammatory effect”. Tests of heparin will be highly anticipated because it is already widely used, shown to be widely tolerated, and is naturally occurring and therefore can be produced cheaply in huge quantities if proven to be effective.
Bemcentinib, a tablet developed by the Norwegian company BerGenBio, which is used to treat blood disorders. “It has been shown, almost by chance, to have a potent antiviral effect” to reduce infection in experiments on a number of viruses including Ebola and Sars coronavirus-2, said Wilkinson. It appears to work by preventing the virus infecting the cells but also by reducing its replication within healthy cells by keeping the innate immunity created by type 1 interferon proteins active. Healthy cells usually “switch off the entire machinery so the virus can’t hijack it”, said Wilkinson, but Covid-19 “subverts this” and this drug may help cells against viral attack, he added.
Medi3506, an anti-inflammatory injection being developed for skin disorders and chronic obstructive pulmonary disease, but which has also been used in trials for asthma by AstraZeneca. It acts to dampen down the cytokine storm that causes the immune system to go into overdrive and cause fever, inflammation and fatigue.
Calquence, another AstraZeneca drug, used to treat mantle cell lymphoma. It acts as an inhibitor of the enzyme known as Bruton’s tyrosine kinase (BTK) and was developed for severe lung inflammation. It was chosen for a formal trial after anecdotal evidence showed a reduced incidence of complications from Covid infection or severe lung injuries.
Zilucoplan, a drug developed by the Belgian biopharma company UCB, which is already in trial for potential treatment of myasthenia gravis, a skeleto-muscular disorder. Hopes centre on its ability to stop the overactivation of “complement cascade”, part of the immune system that can kill cells and lead to catastrophic lung and tissue damage. “A lot of the damage is focused on the blood cells and the very small blood vessels in the lung.”
The drugs were chosen from a list of 200 potential candidates and if they do not work for Covid-19, another batch will then be considered for trials. Should the trials deliver positive results, they will feed into the later-phase national research programme being run by Oxford University.
While reducing Covid-19 infection is everyone’s goal, falling patient numbers present a problem for scientists researching treatments and vaccines. “That is why it is important to get every single patient you can into a trial and that is an important message. If a patient is eligible for any of the studies, whether it be a Accord or vaccine studies or other drug trials, they should be offered the opportunity to take part as we know that they’re making a very valuable contribution to their own health and also to public health,” said Wilkinson.
Sixty patients per drug will need to be assessed over the next few months and Wilkinson said that, if needed, researchers would look to work with other countries and possibly coronavirus patients who are not sent to hospital but have strong symptoms.