To complement the Covid-19 vaccines that have proven to be highly effective, pharmaceutical companies worldwide are working on medications to treat the viral disease. They could be a further tool in efforts to halt the pandemic, and help protect people who haven’t been – perhaps because they can’t be – vaccinated.
No drug has yet been developed specifically for the novel coronavirus and approved for all patients. So doctors are repurposing existing therapeutics in treating certain Covid-19 complications in some cases. Many hospitalized patients are given a blood thinner, for example, because Covid-19 increases the risk of thrombosis, heart attack and stroke. And antibiotics are often administered to protect against possible bacterial infections.
The difficulty in treating Covid-19 lies in the biology of the virus, Swiss molecular biologist Emanuel Wyler recently wrote in the Berliner Zeitung newspaper. If you contract the SARS-CoV-2 virus, there are initially no symptoms, he says.
“When, among other things, you then get a cough or sore throat, in most cases your immune system has already begun to fight the virus,” writes Wyler, who does research at the Berlin-based Max Delbrueck Centre for Molecular Medicine. “As with the flu, medications directly targeting the virus therefore often come too late.”
The only such medication that has received conditional marketing approval in the European Union (EU) so far (in July 2020) is remdesivir, developed by the US biopharmaceutical company Gilead Sciences and sold under the brand name Veklury. Its use is indicated solely for the treatment of Covid-19 in adults and adolescents (aged 12 years and older and weighing at least 40 kg) with pneumonia requiring supplemental oxygen but no invasive ventilation.
Originally developed for the treatment of Ebola virus, remdesivir was found to inhibit the replication of a wide range of human and animal coronaviruses. In November 2020, however, the World Health Organization (WHO) issued a conditional recommendation against the use of remdesivir in hospitalized patients, regardless of disease severity, saying there was currently no evidence that it improved survival and other outcomes in these patients.
And in mid-September, Germany’s Federal Joint Committee (G-BA), the highest decision-making body of the country’s physicians, dentists, hospitals and health insurance funds, assessed remdesivir as having little effect in people with moderate cases of Covid-19 and none at all in severe cases.
Although the anti-inflammatory medication dexamethasone hasn’t received official EU approval for use against the novel coronavirus, doctors in Germany have been giving it to some hospitalized patients. Wyler calls it “a central medication for the treatment of Covid-19.” It’s administered to inhibit an excessive immune reaction known as a cytokine storm, a hyperinflammatory phase that often occurs in Covid-19 patients who develop pneumonia.
According to the Robert Koch Institute (RKI), responsible for disease control and prevention in Germany, dexamethasone has been shown to be most effective in Covid-19 patients requiring invasive ventilation. But its use in those with less severe cases of the disease can “even be detrimental,” it warns.
Eight medications for treatment of Covid-19 are currently in various stages of the approval process by the European Medicines Agency (EMA). They include antibody drugs that are already being used for mild cases of the disease.
Used in special cases, for instance, is a “cocktail” of the monoclonal antibodies casirivimab and imdevimab, developed by the US biotechnology company Regeneron Pharmaceuticals and Swiss healthcare concern Roche, and sold under the brand name Regn-CoV2. It’s the first medication recommended by the WHO for patients at high risk of progressing to severe Covid-19, and for those severely ill with no natural antibodies.
Monoclonal antibodies are laboratory-made proteins that mimic natural antibodies produced by the body to fight off infections – “monoclonal” because they’re made by cloning a unique white blood cell. They’re designed to attach to the spike protein of SARS-CoV-2 at different sites. When they do, the virus is unable to enter the body’s cells. The EMA is reviewing available data on the use of four monoclonal antibodies in all, which are time-consuming and expensive to generate.
Dr Christian Drosten, head of the Institute of Virology at Charite University Hospital in Berlin, said in his regular Covid-19 podcast that administration of monoclonal antibodies to treat the disease was “almost always too late,” namely when the virus had already multiplied widely in the body. For the average patient, this is essentially true by the time symptoms appear, he remarked.
A recent clinical trial of the long-acting antibody (LAAB) combination AZD7442, produced by the British-Swedish biopharmaceutical company AstraZeneca and also known as Evusheld, showed that it reduced the risk of symptomatic Covid-19 by 77 per cent. In mid-October, the EMA began a rolling (ie. expedited) review of Evusheld. The EMA is also evaluating two additional treatments for Covid-19, both of which have already been approved for other illnesses, such as rheumatoid arthritis.
Molnupiravir, an antiviral pill by the US pharmaceutical giant Merck, recently made headlines when the company announced that it had cut hospitalizations and deaths among people with Covid-19 by half in a clinical trial. Similar to remdesivir, the drug inhibits replication of SARS-CoV-2 inside a person’s cells. Merck says it plans to seek emergency use authorization in the US as soon as possible, and to submit marketing applications to regulatory bodies worldwide.
The medication ivermectin, an anti-parasitic (eg intestinal worms in horses and cows) with approved uses in both animals and humans, has been touted in some circles as an antidote to Covid-19. A comprehensive analysis of several studies found no evidence of effectiveness, however. Nor have the anti-malarial drugs hydroxychloroquine und chloroquine been shown to be effective in preventing or treating the disease.