While remdesivir reduces the mortality rate and the duration of the illness COVID-19, it's no magic remedy. But the USA has just given it special approval to treat patients in hospitals.
Soon after the very first cases of coronavirus infections in China, attentions turned to remdesivir as a potential drug to treat the illness. Remdesivir was originally developed to treat Ebola infections, but it also showed effectiveness against SARS and MERS coronaviruses in laboratory tests. The new SARS-CoV-2 is considered a variant of the 2002 SARS pathogen.
The drug was developed by the US pharmaceutical company Gilead Sciences as GS-5734. Not a single country had approved it.
But now, following positive results in a first clinical trial, the U.S. Food and Drug Administration has given remdesivir special approval. It can be administered in American hospitals to treat selected patients suffering with the lung disease COVID-19. That's separate from any further clinical trials. Gilead Sciences says it will donate 1.5 million doses of remdesivir.
The antiviral effect of remdesivir derives from its function as a so-called nucleotide analogue. The active substance inhibits the RNA polymerase (RdRp) of viruses such as Ebola and MERS because its structure is similar to RNA building blocks. During virus replication, these are erroneously incorporated into the genetic strands of the new virus copies. Truly functional new viruses cannot be created in this way.
Although remdesivir did not prove to be really effective in fighting Ebola, cell culture experiments and initial experiments on macaques showed that it had a promising effect against the coronaviruses SARS and MERS-CoV, which are closely related to SARS-CoV-2.
Recent clinical trials with remdesivir carried out in the USA and China were intended to show whether the drug also helps against COVID-19.
White House celebrates positive effects
First positive results of the randomized clinical trial in the USA were announced on Wednesday (29.04.) directly from the White House in Washington DC. Speaking of remdesivir at a press conference with US President Donald Trump at the White House, the director of the National Institute for Allergy and Infectious Diseases (NIAID), Anthony Fauci, said: "This will be the standard of care."
A total of 1,063 patients with varying degrees of severity of the disease took part in the NIAID-funded study "Adaptive COVID-19 Treatment Trial" and were treated with remdesivir or a placebo for 10 days.
In such a randomized double-blind study, neither the treating physicians nor the patients know who is injected daily with the active substance and who receives a placebo. This is to prevent any expectations had of the drug from possibly distorting the actual results.
According to NIAID, preliminary results suggest that COVID-19 patients receiving remdesivir had, on average, a 31% faster recovery time than patients given the placebo. Patients receiving remdesivir had an average recovery time of 11 days and patients receiving the placebo had an average recovery time of 15 days.
The mortality rate in the remdesivir-treated group was 8% compared to 11.6% in the placebo group.
Trials terminated prematurely
Those responsible for the trials considered them sufficient. The National Institutes of Health said that the results were meaningful enough. At a meeting of the Data Safety Monitoring Board (DSMB) on April 27, it was decided to terminate the study prematurely.
Nevertheless, President Trump's adviser also conceded that the results of the study must now be reviewed by independent experts (peer review).
In parallel with the success reports from Washington, there were sobering reports from China, where remdesivir was first tested for its efficacy in randomized clinical trials in Wuhan on patients in intensive care units suffering from severe cases of COVID-19.
Eventually, however, Wuhan lacked the necessary patients because of a sharp decline in new infections, and that study was also terminated prematurely, according to a report in The Lancet. Currently, the much-cited map put out by the Johns Hopkins University showing confirmed COVID-19 cases around the world indeed shows no red dot at all near Wuhan.
What do the results mean?
In the two studies, the active substance remdesivir has clearly proven to be moderately effective. It reduces the death rate slightly but not really significantly. And it reduces the duration of the disease by a few days.
Although this is encouraging, it is far from being the resounding success that many had hoped for from the most promising drug candidate to date.
German infectious disease expert, Professor Gerd Fätkenheuer at the University Hospital of Cologne, had expected a quick approval for remdesivir after the publication of the NIAID study. He is leading a clinical trial of remdesivir with patients in Germany. "For patients with a severe form of this disease, this study gives hope that they will be able to recover from the infection more quickly and safely," said Prof. Fätkenheuer.
However, he said that "in the foreseeable future there will not be enough of the active substance available. It will therefore be urgently necessary to investigate further active substances in clinical trials. But the yardstick for their effectiveness will, in the future, be remdesivir."
Prof. Clemens Wendtner, chief physician for infectiology and tropical medicine and head of the special unit for highly contagious, life-threatening infections in Munich, sees things similarly. "Since neither lopinavir/ritonavir nor hydroxychloroquine were able to fulfill the expectations had of them, remdesivir will now have to serve as a reference substance in future drug developments for COVID-19, despite some reservations," said Wendtler.
"Future studies will have to show to what extent remdesivir can also be used as a combination partner with other substances in order to further increase efficiency," he said.