Rise, fall and rise of remdesivir, the antiviral “hopeful” to combat covid-19.
Remdesivir It 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, pre-commercialization, and that determines if a drug will be generally effective to fight a disease).
In just a few days, however, opinions on this drug have only fluctuated, fluctuations that have also been reflected in Gilead’s stocks (which, in turn, may be further fueling these fluctuations).
What do we know about remdesivir
Despite the fact that stocks have risen like foam and there is a lot of expectation around them, there is still no need to launch the campaigns on the fly. First, you have to remember one important thing: remdesivir, the antiviral from the biotech company Gilead Science, was initially developed to combat the ebolavirus, which causes Ebola … and failed. However, the company began its tests with SARS-CoV-2 because Remdesivir had demonstrated antiviral activity against other viruses, such as Marburg virus, respiratory syncytial virus, Junín virus, Lassa fever virus and MERS-causing coronavirus.
In the words of the same pharmaceutical company, we are facing a “nucleotide analog with broad-spectrum antiviral activity.” Translated into roman paladino, 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.
Second, we may be witnessing a master move by a pharmaceutical company not so much to seek a cure but to obtain huge profits, as some analysts denounce. 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 the trial is published in a scientific journal.
However, the study, carried out by the National Institute of Infectious Diseases (Niaid), a branch of the National Institutes of Health (NIH), has led the United States Food and Drug Administration (FDA) last Friday approve of emergency the use 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 one 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.
To this is added another investigation carried out with remdesivir that has not offered results beyond placebo, and that has appeared just at the worst time for Gilead. The study has been carried out in Wuhan hospitals by Chinese researchers and has been published in The Lancet.
The Wuhan Trial
As published in The Lancet, a randomized trial compared to placebo conducted in hospitals in Wuhan (China), in which the 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, this new data has caused Gilead shares to plummet once again on the stock market, even though they had previously grown dramatically.
Perhaps to counter this drop in confidence from remdesivir (Because it is suspicious that data only appears after the Wuhan trial result is published), provisional data collected before the National Institute of Infectious Diseases (NIAID) clinical trial has been quickly echoed.
Provisional data from the NIAD study progress (neither reviewed by independent experts nor published in a scientific journal) indicate that, of 1,063 critically ill hospitalized for COVID, those 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 placebo. However, the own Anthony Fauci, director of the NIAID, has recognized that this result does not have statistical support.
The own Anthony Fauci, director of the NIAID, has recognized that this result does not have statistical support.
With everything, Gilead has already reported that it expects to have results from another trial, this with mild patients, at the end of May, and the director of Emergencies of the World Health Organization, Mike Ryan, has described as a “ray of hope” the results of the recent clinical trials of the drug remdesivir.
Killing flies with cannon shots
Unfortunately, antivirals have a certainly limited effect: malfunction when the disease is in the acute phase. And by the time a patient is symptomatic with a virus, they usually already have a high viral load. In such a case, when an antiviral is administered to someone who is already ill, the damage of the virus is already very advanced because it has had time to colonize the body.
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 inside us, making the words of the Nobel Prize more valid than ever. Peter medawar about what a virus is: “bad news wrapped in a protein.” Outside of living cells, viruses are simply inert objects that do not eat, breathe, or do practically anything. They sneak into an organism by chance and that is when they begin to bloom and reproduce rapidly.
Outside of living cells, viruses are simply inert objects that do not eat, breathe, or do practically anything.
Despite the constant threat, however, a field in which medicine has traditionally been weak when it comes to finding drugs to treat viral infections, basically because it is required to gather a series of very particular characteristics, among other:
- Be specifically active against the virus, inhibiting some essential step in its metabolism.
- Having certain parameters that allow the drug to be of high oral bioavailability.
- It has a rapid penetration into infected tissues and non-toxic for normal cells.
- It must be excreted without being metabolized or without generating toxic metabolites.
This strenuous effort, then, forces many promising antivirals ultimately are not particularly useful. In fact, the situation we are experiencing with remdesivir begins to look too much like what happened with the famous Tamiflu, a flu antiviral, another prodrug such as remdesivir (a prodrug is a drug or compound that, after administration, is metabolized, that is, converted within the body, into a pharmacologically active drug).
Claims defending Tamiflu’s efficacy against complications were a key factor in the decisions made by governments around the world to stockpile these drugs in the 2009-2010 pandemic. Nevertheless, subsequent independent reviews confirmed the worst prognoses: Tamiflu decreased flu symptoms for half a day 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, acute bronchitis / bronchitis, respiratory tract infections, insomnia, rhinorrhea, cough, vertigo, vomiting, abdominal pain, diarrhea, dyspepsia, dizziness , tiredness, pain …
The latest update is based on a review of the 20 full internal trials reports for Tamiflu (oseltamivir) and 26 for Relenza (zanamivir). Until then, 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.
For the moment, remdesivir side effects do not appear to be as severe, at least in these essays, which is at least a little hopeful. But while stocks go up and down 500 points, it is still too early to be sure, and the whole world is still watching the results that are coming through discovery and, also, of marketing movement. We will see how it all ends.
At least, to heal ourselves 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 in. We are fighting viruses, it is what it touches: You don’t have to gamble everything on a single card, or put all your eggs in one basket.
