Florence Cunzolo
04/30/2020 - 15:56
- Clarín.com
- Good Life
After his health worsened as a result of the infection with the new coronavirus, an American was experimentally treated in January with remdesivir, a drug originally developed for Ebola and currentlyIt is not authorized for any disease anywhere in the world. The next day, her clinical condition improved.
But to move from anecdotal case to solid evidence that could support the recommendation of the drug in the treatment of Covid-19, large clinical trials (involving many patients) and controlled trials (in which the intervention was compared with the standard treatment) were needed. or placebo) that demonstrate its safety and efficacy.
Some of those studies began to yield results that, at the moment, do not offer a conclusive panorama : the same day that an article was published on a trial in China that did not find statistically significant benefits, in the United States they announced preliminary results of a study with About 1,000 patients evaluated as promising, to the point that the Federal Food and Drug Administration (FDA) could issue an authorization to allow its emergency use.
The news came almost simultaneously. Yesterday morning an article was published in The Lancet - the result of which had been leaked days before - with the discouraging Chinese experience. Hours later, the largest reference in infectious diseases in the United States and one of the most prominent figures in the area worldwide, Anthony Fauci, described as "very optimistic" the data from a trial of more than 1,000 patients conducted in that country with the A drug that, he said, "has been shown to block the virus."
Remdesivir is a broad-spectrum antiviral developed by Gilead Sciences that inhibits the virus replication process in the body . The results for the treatment of Ebola virus infection, for which it was conceived, were unsatisfactory. In vitro studies (in cells) and in animal models showed promise for treating SARS-CoV-2 infection (the virus that causes Covid-19). It was also tested in healthy volunteers and in animal models against multiple viral pathogens including MERS and SARS, other coronaviruses. Now he is faced with the chance of having some activity against the new family member who unleashed the current pandemic, for which there is no vaccine or specific treatment and that has already caused more than 3.2 million cases in the world.
Fauci is director of NIAID and advises the White House on managing the pandemic. / Evan Vucci / AP Photo /
Chinese disappointment
The clinical trial conducted in China was carried out in 10 hospitals in Hubei province (where Wuhan, the city where the outbreak started), between February 6 and March 12, a period in which 237 patients with Severe conditions were enrolled and randomly assigned to two treatment groups: 158 received remdesivir and 79 placebo (a drug-inert substance) intravenously.
"They used an adequate population of patients, with radiological lung and oxygenation compromise, before they have 12 days of symptoms, to act when the virus is replicating, because the more time passes, the less it replicates," the infectologist explained to Clarín. Martín Stryjewski, Head of Hospitalization at the Pombo de Rodríguez University Hospital of CEMIC and member of the Argentine Society of Infectious Diseases (SADI).
The patients were followed for 28 days and the success of the intervention was measured by the time until clinical improvement, which is determined by dropping two points on a scale of six, in which 1 is medical discharge and 6 is death.
"After 10 days of remdesivir, what he observed is that the clinical recovery time was 21 days for those who received the drug and 23 days for those in the placebo group, there is no statistical difference. Mortality was 14% in the In the first group and 13% in the other, there is no difference either and the viral load in the throat of the patients does not vary, "says Stryjewski, a former fellow in Infectious Diseases and a master in Clinical Research at Duke University, in the United States.
The authors of the study concluded that the use of remdesivir was not associated with a difference in time to clinical improvement, nor with statistically significant clinical benefits. However, they clarified that the trial did not reach the predetermined sample size (they were looking for 325 patients and there were 237) because the disease outbreak ended up being controlled in China. They also stated that more studies with remdesivir are needed , evaluating early treatment in patients with Covid-19 and higher dose regimens, or in combination with other antivirals or neutralizing antibodies to SARS-CoV-2 in severe cases to understand the better its potential effectiveness.
" It is a negative clinical trial . No effect is seen in clinical cure, viral load, or mortality," says Stryjewski, who spent 15 years involved in the development of new drugs. However, he concedes that the study lost some power by concluding earlier than expected, but in the data analyzed "there is no sign of a difference."
Optimism in the United States
Only preliminary results were known from the study carried out in the United States , which were not yet submitted to peer review or published in a scientific journal.
The trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), reporting to the National Institutes of Health (NIH), began on February 21. According to the interim report of the randomized controlled trial with 1063 patients with advanced Covid-19 and lung involvement (similar to the criteria used in China), those who received remdesivir recovered 31% faster than those who received placebo (11 days vs. 15). The data also "suggested a survival benefit," with a 8.0% mortality rate for the group receiving remdesivir vs. 11.6% for the control group.
"Regarding recovery time (what does this mean? What gave them negative? That they did not die? Who was discharged? Who left the hospital?), Four days apart without knowing at what point in the infection and under what conditions the patients started the trial does not seem very significant ", analyzes in dialogue with Clarín the doctor in biochemistry Hugo Luján, director of the Center for Research and Development in Immunology and Infectious Diseases (CIDIE), which belongs to CONICET and to the Catholic University of Córdoba (UCC).
On the impact on mortality, says Stryjewski: "Perhaps with a little more patients this could be significant, but I don't see a big difference, so the effect is not huge if it existed."
And he concludes: "You have to wait for the results to really see how the patients were, what happened to them, what the viral loads were like, how the analysis of mortality and adverse effects were. Because in the study by The Lancet there were more patients who discontinued medication in the remdesivir arm than in the placebo arm, and in the NIAID study those data are missing, so it is very preliminary. For now there is a sign and, although it is a hope, it does not seem decisive. It may have an effect on the disease, but that effect does not seem greater, with which although it may help us to treat patients with Covid in the future, it does not seem that it will be a silver bullet ".
Along the same lines, Luján highlights that "the results in the two studies were not black or white; and given that the clinical manifestations of Covid-19 can be white, black, or any other color, it is very difficult to measure effectiveness in these difficult conditions and where everyone wants to appear being the first to find something (or discard it if they discovered it in another country) ". Beyond that, he claims that drugs that inhibit RNA-dependent RNA polymerase (such as remdesivir) and viral protease inhibitors are the most promising candidates with the fewest adverse reactions for the treatment of the disease.
For the Argentine molecular biologist and biotechnologist Ernesto Resnik, the preliminary results of the study carried out in the United States - where he is installed - could be "very good news", but he agrees that we must wait for the publication of the final report. " It seems that it can help control Covid-19, but it is not the panacea that we would like, that of curing the disease in all its manifestations. "
As announced, more detailed information on the trial results will be available in a future report. From the NIAID they noted that the FDA has sustained and continuous talks with the pharmaceutical company Gilead to make remdesivir available to patients "as quickly as possible," something for which President Donald Trump lobbied.
The company - whose shares skyrocketed after the announcement - issued a statement recalling that the antiviral is not yet licensed or approved anywhere in the world and that "it has not yet been shown to be safe or effective for the treatment of Covid -19 ". They also noted that in late May they will share additional data from an open-label phase 3 trial in critically ill patients. "It will provide information on whether a shorter duration of therapy, of 5 days, may have efficacy and safety similar to that of the 10-day treatment evaluated in the NIAID trial and other ongoing trials."
Remdesivir is, in addition, one of the four therapeutic schemes that will be evaluated in the mega Solidarity trial, launched by the World Health Organization, in which Argentina participates.