Faced with an unfamiliar enemy, doctors treating coronavirus patients have had no choice but to reach for familiar pharmaceutical weapons. But so far few have proven effective, and then only for treating the severely ill. Intense efforts are now under way to bolster the arsenal, either by developing new treatments or repurposing old ones.
The World Health Organization’s ongoing review of Covid-19 studies reports 1,905 randomised trials of potential treatments at the time of writing. Yet some of these are very small, involving no more than 10 patients, and are unlikely to deliver robust conclusions. “For small studies there are always problems,” says the Wellcome Trust’s Nick Cammack. “You never get definitive answers. When it goes into the larger studies, things that seem to work actually don’t.”
He adds, however, that they can still yield useful insights, and that other
Covid-19 trials are more substantial. “It’s great that there are big studies up and running,” he says.
When the WHO last month recommended the use of corticosteroids for treating Covid-19 patients, the move followed careful scrutiny of multiple trials. One of the scientists involved was Jonathan Sterne, professor of medical statistics and epidemiology at the University of Bristol, who was approached by the WHO in April and became lead author of the resulting meta-analysis, which was published on September 2. “This was a record-breaking pace for us,” says Prof Sterne.
According to Prof Sterne, corticosteroids are currently the only class of drug proven to reduce Covid-19 mortality in critically ill patients. One of the best known is dexamethasone, which has been approved by EU regulators for treating Covid-19 patients. President Donald Trump was also given it after he became infected.
Yet the WHO does not recommend corticosteroids for people who have only mild symptoms. “Steroids only reduce mortality in really sick patients,” says Prof Sterne. “We don’t have anything for before the disease progresses.”
Similarly, remdesivir, the only other drug that has received broad regulatory approval for treating Covid-19, is not used in mild cases. An antiviral medication developed for Ebola, it helps reduce the recovery time for severely ill patients.
Researchers are, however, trying to find drugs that can be used in milder cases. Along with the Bill & Melinda Gates Foundation and Mastercard, the Wellcome Trust has launched the Covid-19 Therapeutics Accelerator to focus on this area. Among the research it is investing in are studies of hydroxychloroquine — the antimalarial drug championed earlier this year by Mr Trump.
While the US Food and Drug Administration has withdrawn its approval for the use of hydroxychloroquine in treating hospitalised patients, Mr Cammack says it is still necessary to explore all of the drug’s potential benefits. Several of the Therapeutics Accelerator studies are examining hydroxychloroquine’s use as a protective measure for healthcare workers — though Mr Cammack notes that “the politicalisation of chloroquine” temporarily halted one trial.
As well as repurposing existing drugs to fight coronavirus, scientists are also trying to develop new ones. “There will be increasing evaluations of these,” says Prof Sterne.
So-called monoclonal antibodies, laboratory-made versions of the body’s natural defences, have attracted a lot of attention. Though this type of therapy was first developed in the 1980s, researchers have been racing to engineer antibodies that will prevent coronavirus from binding to cells.
“I think at the moment this is the most promising class of drug,” says Peter Horby, professor of emerging infectious diseases and global health
at the University of Oxford and chair of the UK government’s New and Emerging Respiratory Virus Threats Advisory Group.
REGN-Cov-2, a monoclonal antibody treatment developed by American biotechnology company Regeneron, is currently the subject of four late-stage clinical trials worldwide. One of these is the UK’s Recovery Trial, a large-scale initiative to evaluate Covid-19 treatments. Prof Horby says that, of six different monoclonal antibody products considered for the trial, REGN-Cov-2 was the most advanced.
Regeneron’s drug won praise from President Trump this month when it was also administered to him. Describing it as a “cure”, he promised to make it and the other treatments he received freely available to patients in need.
That would be good news for patients in the US if that were to happen — though the FDA has yet to approve REGN-Cov-2 — but patients in poorer countries are unlikely to be so lucky. Production, pricing and distribution issues can all hinder the developing world’s access to innovative drugs.
Mr Cammack predicts that if the antibodies are successful, it will not be until the second half of next year that it will be possible to “scale them up” enough to distribute globally. Until then, he believes it is worth continuing to investigate pre-existing drugs, even if they are not as effective. “If you actually save a life, it’s a massive step forward,” he says.
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