Soon after the very first cases of coronavirus infections in China, attention 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. At the outset of the pandemic, it was not approved by any country.
It has since been used in the context of an Emergency Use Authorization (EUA), as well as in the context of scientific studies in numerous countries. Gilead Sciences gave the drug the brand name Veklury in Autumn 2020.
After an initial clinical trial in the US showed positive results in May 2020, the US Food and Drug Administration (FDA) granted the EUA. Since then, Remdesivir was used in hospitals for the treatment of individual patients with the lung disease COVID-19 outside of clinical trials.
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Gilead Sciences made this clear again in a statement on October 15, 2020. The day before, the Financial Times quoted a hitherto unpublished World Health Organization (WHO) study showing that Remdesivir barely reduces the mortality of COVID-19 patients. The study is a result of the so-called ‘SOLIDARITY Trial’ in which the data of 11,266 patients was evaluated. The WHO has not commented on the leak.
However, Gilead Sciences argued that by having the study leaked, “the data from this open-label global trial have not undergone the rigorous review required to allow for constructive scientific discussion.”
In the same statement, the companyreferenced another study with 1,062 volunteers, which was recently published in the New England Journal of Medicine (NEJM), and showed that Remdesivir could reduce the average healing time from 15 to 10 days.
Gilead Sciences filed an application for regular approval of the drug with the FDA on August 7, 2020. It has not yet been approved.
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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.
Early clinical trials with Remdesivir carried out in the US and China were intended to show if the drug also helps against COVID-19.
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Initial positive results of an early randomized clinical trial in the US were announced on April 29, 2020, directly from the White House in Washington, DC. Speaking about 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, then stated: “This will be the standard of care.”
A total of 1,063 patients with varying degrees of severity of the disease had taken part in the NIAID-funded study, the “Adaptive COVID-19 Treatment Trial”‘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 of the drug from possibly distorting the actual results.
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The results were similar, albeit not quite as clear as those from the new NEJM study. According to NIAID, preliminary results suggested that COVID-19 patients receiving Remdesivir had, on average, a 31% faster recovery time than patients given the placebo. Patients that received 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.
Those responsible for the trials then considered them sufficient. The National Institutes of Health in the US said that the results were meaningful enough. At a meeting of the Data Safety Monitoring Board (DSMB) on April 27, 2020, it was decided to terminate the study prematurely.
In parallel with the successful reports from Washington, there were additional 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.
There are now too few patients at the source of the coronavirus pandemic in Wuhan
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.
Both the early two studies, as well as the more recently published and leaked studies, seem to point to the same conclusion: The active substance Remdesivir has clearly proven to be moderately effective. It reduces the death rate slightly but not 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 what was described as the most promising drug candidate to date.
German infectious disease expert, Gerd Fätkenheuer, professor of medicine at the University Hospital Cologne, had expected a quick approval for Remdesivir after the publication of the NIAID study in May. He was 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,” he said. “The yardstick for the effectiveness of potential other drugs will, in the future, be Remdesivir.”
Clemens Wendtner, chief physician for infectiology and tropical medicine and head of the special unit for highly contagious, life-threatening infections at the Munich Municipal Hospital, drew a similar conclusion. “Since neither lopinavir (ritonavir) nor hydroxychloroquine were able to fulfill expectations, Remdesivir will now have to serve as a reference substance in future drug developments for COVID-19, despite some reservations,” said Wendtner in May.
“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.
This article was originally published on 30 April 2020 — before Remdesivir was approved. It has since been updated to include the latest information from recent scientific studies.
This article was translated from German.
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The German physicist Johann Wilhelm Ritter not only discovered ultraviolet radiation in 1801, but also invented the first battery the following year. Ritter was also interested in galvanism — a term applied to muscle contractions caused by electric shocks. The fact that he died at the age of 33 is said to have been due in part to the galvanic self-experiments with which he maltreated his body.
The Austrian psychologist and doctor Sigmund Freud is known as the founder of psychoanalysis. His methods are still used, discussed and criticized today. Less well known is that Freud researched the effects of cocaine during his time as a doctor at the Vienna General Hospital. Published letters show that Freud himself consumed coke for a long time and in large quantities.
“I believe that I am on the trail of the true pathogen,” wrote the American physician Jesse Lazear on September 8, 1900, in a letter to his wife. Lazear researched malaria and yellow fever. He confirmed that the latter is transmitted by mosquitoes. To study the disease, he intentionally allowed himself to be stung, fell ill and died 17 days after writing the letter. Lazear was only 34 years old.
John Paul Stapp became known as the “fastest man on earth” because of his research on the effects of acceleration forces on the human body — including his own: He had himself accelerated on a so-called rocket sled up to more than 1,000 kph (621 mph) and decelerated completely in 1.4 seconds. It is the highest acceleration that a human being has ever voluntarily withstood.
Werner Forssmann was already considered a troublemaker during his medical training. The German surgeon was determined to prove that a long, flexible catheter could be inserted safely from the crook of the arm to the heart. Although his superiors had expressly forbidden him to carry out the experiment, in 1929 Forssmann was the first person to try it out — on himself. Secretly, of course.
The Canadian physician Ralph Steinman fell ill with pancreatic cancer and underwent an immunotherapy he developed himself. According to his physician, this therapy was unable to prevent Steinman’s death, but — contrary to the prognosis — could possibly have prolonged his life by over four years. Steinman died in 2011, a few days before the Nobel Prize was awarded, which he received posthumously.