Rise, fall and rise of remdesivir, the antiviral "hopeful" to fight covid-19

Remdesivir is the great white hope, although perhaps all that glitters is not gold. As we already explained, this drug, from the Gilead brand, is the only antiviral against SARS-CoV-2 that is already in clinical phase III (the last one, prior to marketing, and which determines whether a drug will be effectively general to fight a disease).

In a few days, however, opinions on this drug have only fluctuated, fluctuations that have also been reflected in Gilead's stock stocks (which, in turn, may be fueling those fluctuations even further).

What we know about remdesivir

Despite the fact that the actions have risen like foam and that there is a lot of expectation around them, we still do not have to launch the fields in flight. First of all, one important thing to remember: Remdesivir, the antiviral from biotech company Gilead Science, was originally developed to fight Ebolavirus, the cause of Ebola ... and failure. However, the company started its tests with SARS-CoV-2 because Remdesivir had demonstrated antiviral activity against other viruses, such as Marburg, respiratory syncytial, Junin virus, Lassa fever virus and coronavirus causing MERS.

In the words of the same pharmaceutical company, we are dealing with a "nucleotide analog with broad-spectrum antiviral activity". Translated into Roman paladin, it works by inactivating an enzyme that some viruses need to replicate.

The problem, then, is that due to the urgency of the situation, we may be facing a mirage.

Secondly, we may be witnessing a master move by a pharmaceutical company, not so much to seek a cure but to obtain great benefits, as some analysts denounce. As of today, its exact mechanism of action has not yet been described. And since we are facing an emergency route because we need treatment as soon as possible, the results still need to be reviewed by independent researchers and that the trial is published in a scientific journal.

All in all, the study, carried out by the National Institute of Infectious Diseases (Niaid), a branch of the National Institutes of Health (NIH), has led to last Friday the United States Food and Drug Administration (FDA) emergency approval of remdesivir. On Thursday, Gilead announced that it expects to produce more than 140,000 doses of its 10-day remdesivir treatment by the end of May, and that it will be able to produce a million of them by the end of the year.

The problem, then, is that due to the urgency of the situation, we may be facing a mirage.

Added to this is another study conducted with remdesivir that has not offered results beyond placebo, and that has appeared just at the worst time for Gilead. The study has been conducted in Wuhan hospitals by Chinese researchers and has been published in The Lancet.

The Wuhan Trial

As published in The Lancet, a randomized placebo-controlled trial conducted in hospitals in Wuhan, China, in which treatment was administered to 237 patients, has not shown significant efficacy of remdesivir.

In this case, the work has been reviewed by independent experts, and the results show that remdesivir does not provide any advantage to patients hospitalized with covid. Naturally, these new data have caused Gilead's shares to plummet again on the Stock Market, despite previously having grown dramatically.

Perhaps to counteract this drop in confidence of remdesivir (because it seems suspicious that data will just appear after the results of the Wuhan trial are published), they have quickly echoed provisional data collected before the National Institute of Infectious Diseases clinical trial (NIAID) is finished.

Provisional data from the progress of the NIAD study (neither reviewed by independent experts nor published in a scientific journal) indicate that, of 1,063 seriously ill patients hospitalized for COVID, those who were treated for remdesivir recovered 31% earlier than those taking placebo, or 11 days versus 15, respectively. The NIAID has also published that mortality is 8% among those taking the antiviral and 11.6% among those taking the placebo. However, Anthony Fauci himself, director of the NIAID, has recognized that this result does not have statistical support.

NIAID director Anthony Fauci himself has acknowledged that this result is not statistically supported.

However, Gilead has already reported that he expects to have results from another trial, this one with minor illnesses, at the end of May, and the director of Emergencies of the World Health Organization, Mike Ryan, has described as "ray of hope" the results of recent clinical trials of the drug remdesivir.

Killing flies with cannon shots

Unfortunately, antivirals have a certainly limited effect: they work poorly when the disease is in the acute phase. And by the time a patient is symptomatic of a virus, they generally already have a high viral load. In such a case, when an antiviral is administered to someone who is already sick, the damage of the virus is already very advanced because it has had time to colonize the organism.

The way to attack viruses, then, is frankly crude. Not surprisingly, there are a good handful of human pathogens out there, and much of their existence is aimed at developing new and cunning ways to penetrate within, making the words of Nobel Prize winner Peter Medawar more valid than ever. which is a virus: "bad news wrapped in protein." Outside of living cells, viruses are simply inert objects that do not eat, breathe, or do virtually anything. They sneak into an organism by chance and it is then that they begin to flourish and reproduce quickly.

Outside of living cells, viruses are simply inert objects that do not eat, breathe, or do virtually anything.

Despite the constant threat, however, a field in which medicine has traditionally been weak in finding medicines to treat viral infections, basically because it requires gathering a series of very particular characteristics, among others:

  • Be specifically active against the virus, inhibiting some essential step of its metabolism.
  • Having certain parameters that allow the drug to be of high oral bioavailability.
  • That it has a fast penetration in the infected tissues and non-toxic for normal cells.
  • It must be excreted without being metabolized or without generating toxic metabolites.

This foolish effort, then, forces many promising antivirals to ultimately not be particularly helpful. In fact, the situation we are living with remdesivir begins to resemble what happened with the famous Tamiflu, an antiviral against influenza, another prodrug such as remdesivir (a prodrug is a drug or compound that, after administration, is metabolizes, that is, becomes within the body, a pharmacologically active drug).

Claims defending the efficacy of Tamiflu against complications were a key factor in decisions made by governments around the world to stock up on these drugs in the 2009-2010 pandemic. However, subsequent independent reviews confirmed the worst prognoses: Tamiflu decreased symptoms of the half-day flu but did not reduce hospital admissions or serious complications. In fact, the following side effects have been reported after taking the drug, among others: nausea, headache, bronchitis / acute bronchitis, respiratory tract infections, insomnia, rhinorrhea, cough, vertigo, vomiting, abdominal pain, diarrhea, dyspepsia, dizziness , tiredness, pain ...

The latest update is based on the review of the 20 full internal reports of the Tamiflu (oseltamivir) and 26 Relenza (zanamivir) trials. Until that time Roche and GSK had refused to share their databases with independent researchers and have only relented after enormous pressure from Cochrane and the British Medical Journal.

At the moment, the side effects of remdesivir don't seem to be as severe, at least in these trials, which is at least a little hopeful. But while the shares rise and fall 500 points, it is still early to be sure, and the whole world is still awaiting the results that are coming to the discovery and also to the marketing movement. We will see how everything ends.

At least, to cure us in health, it should be remembered that 50 new treatments, if not more, are currently under development to try to mitigate the pandemic that we have immersed ourselves in.We are fighting viruses, it is what it touches: it is not necessary to risk everything to a single card, nor to put all the eggs in a single basket.

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