Ebola drug remdesivir leads race for effective Covid-19 treatment

After a series of setbacks because of disappointing outcomes in smaller drug trials, the Ebola drug remdesivir has re-emerged as the antiviral treatment with best potential to counter Covid-19.

This follows early indications from a large randomised human trial being conducted in 70 hospitals across the world. It is likely to lead to the US Food and Drug Administration giving it emergency clearance for use in US hospitals.

It coincided, however, with publication by the Lancet medical journal of a small trial in Wuhan, China, which concluded it was ineffective.

So far, the drug produced by Gilead Sciences is the best treatment option before a vaccine emerges. The US government's leading specialist on infectious diseases Dr Tony Fauci announced there was now clear-cut evidence of remdesivir's benefit in reducing the time to recovery with indications it may also reduce death rates.

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This was the trigger to allow patients who were given a placebo to switch to taking the drug.

Adults admitted to hospital with advanced coronavirus who received remdesivir recovered “much faster” than those given a placebo. The data was released by the US National Institute of Allergy and Infectious Diseases, which is leading the trial.

More than 1,000 patients are participating in the study, which began in early April. Recovery meant a patient was well enough to come off oxygen, to be discharged from hospital or to return to normal activity.

Dr Fauci said the trial “shows remdesivir has a clear-cut, significant, positive effect in diminishing the time to recovery”.

Irish immunologist Prof Luke O'Neill of Trinity College Dublin said his reference to remdesivir being "the standard of care" meant "it sets the bar on something that works on Covid-19".

Remdesivir is "an experimental antiviral". It was rapidly pushed through trials for Ebola after showing promising results in the lab, and then rolled out in affected areas of Africa. It was subsequently deemed less effective than monoclonal antibody drugs, which are often used for cancer treatment.

Promising results

It was revived with the Covid-19 outbreak as it showed promising results in preventing Middle East Respiratory Syndrome and Sars, which are also caused by coronaviruses. But those studies have only been done in animals.

Dr Elena K Schneider-Futschik, from the University of Melbourne, said given the absence of other Covid-19 treatments and promising data, “we can assume that the drug may be fast-tracked”.

The Wuhan study indicated no statistically clinical benefit. However, the researchers tested a smaller number of patients – just over 200 – and it was stopped because of a failure to find enough eligible patients. It did show “a numeric benefit”, which was enough for researchers to recommend further study of the drug.

In a commentary published alongside the study, Dr John David Norrie of the University of Edinburgh noted this obstacle may recur during the pandemic, and "pooling data across possibly several underpowered but high-quality studies looks like our best way to obtain robust insight".

“Promising signals from observational data must be rigorously confirmed or refuted in high-quality randomised trials – particularly given that for Covid-19 no proven safe and effective treatments yet exist,” he added.

That is additionally challenging in a pandemic, and temptation to lower the threshold of convincing evidence must be resisted, because adopting ineffective and potentially unsafe interventions risks only harm without worthwhile benefit, while making it even harder to undertake trials to find truly effective and safe interventions, he warned.

Meanwhile, further statistical evidence of a link between BCG vaccination and lower rates of Covid-19 has emerged in a study of 55 countries, covering 62.9 per of the world population, by scientists based at the Hebrew University of Jerusalem.

The study released by Medrxiv before peer review is completed showed “significantly improved Covid-19 outcomes in countries with higher BCG”.

The strongest correlation is attributed to vaccinated under 25s, and “to a lesser degree the middle age group (25-64 years)”, while a correlation with older people was insignificant.

“We propose that BCG immunisation coverage, especially among the most recently vaccinated, may contribute to attenuation of the Covid-19 spread and severity,” they conclude.

Seven clinical trials using BCG vaccine on older people and healthcare workers to evaluate its impact on coronavirus infection are in progress throughout the world.