How they were resurrected by remdesivir, the new hope for COVID-19 patients

How they were resurrected by remdesivir, the new hope for COVID-19 patients

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A vial of the anti-Ebola medication Remdesivir during a press conference at Eppendorf University Hospital (UKE) in Hamburg (Reuters) (POOL New /)

It seemed that the remdesivir, an antiviral drug designed to fight both hepatitis viruses and common respiratory diseases, was intended to be one of thousands of drugs that were unsuccessful in fighting other diseases. This drug was relegated to the garbage dump of drugs forgotten by the scientists who used to defend it.

However, on Friday, the Food and Drug Administration (FDA) issued a emergency approval for remdesivir as a treatment for seriously ill patients COVID-19, the disease caused by the coronavirus.

The story of the rescue and transformation of remdesivir is a testament to the significant share of federal funding, which allowed scientists working in the shadows to continue fundamental research without the obvious financial benefits. This research depends almost entirely on government subsidies.

Mark Denison of Vanderbilt University is one of the few researchers who discovered the potential of remdesivir. Denison began studying coronaviruses a quarter of a century ago, at a time when few scientists studied them; Remember that those that infected humans caused colds, and scientists just wanted to know how they worked.

“We were interested from a biological point of view,” recalls Denison. “No one was attracted from a therapeutic perspective.”

Neither he nor any of the other groups of scientists interested in coronaviruses predicted that a new one would unleash an epidemic that has killed nearly 250,000 people worldwide. The FDA quickly approved remdesivir for emergency use after a government-funded trial showed it slightly improved the health of very serious patients.

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The study carried out in the laboratories of Gilead Sciences, in California (Reuters) (GILEAD SCIENCES /)

The trial, sponsored by the National Institute for Allergy and Infectious Diseases, included more than 1,000 hospitalized patients and revealed that those who underwent remdesivir treatment recovered faster than those who received a placebo: in 11 days and not in 15. But the drug did not significantly reduce case fatality rates.

Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, noted that the results were “a very important proof of concept,” but not a “decisive blow”. On Friday, President Donald Trump praised this drug as “an important treatment” and “truly promising.”

Remdesivir is approved only for use in very serious patients and temporarily; later it must be formally approved. However, some doctors working in intensive care units embraced the drug as an important new weapon to combat a virus that is killing patients around the world.

“It is a very important first step,” said Robert Finberg, chair of the Department of Medicine at the University of Massachusetts School of Medicine.

There was not much about the initial history of the remdesivir, manufactured by Gilead Sciences, indicating that it could offer the hopes that are now held with it.

The coronaviruses have much more ribonucleic acid than scientists thought they had. Many epidemic-causing viruses carry this type of genetic material, and almost all of them constantly mutate. That is why influenza viruses change from year to year.

However, coronaviruses did not change much: its mutation rate is around one twentieth that of other viruses with ribonucleic acid.

In 2007, Denison discovered that coronaviruses have a powerful “correction” system. If an error occurs when copying ribonucleic acid when the coronavirus replicates, it corrects the error. In laboratory experiments, mutant coronaviruses were weaker compared to those without mutations.

Denison and other experts wondered if it would be possible to trick the virus with a drug that bypasses the correction system and obstructs the development of the virus’s ribonucleic acid chain, ending it prematurely.

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(Reuters) (POOL /)

Speaking about this problem in a meeting with other scientists, Denison learned that Gilead Sciences had dozens of medications that could accomplish that. “For one reason or another, all of these compounds had been neglected,” Denison noted.

In laboratory tests, it was found that most managed to deactivate the coronavirus, some better than others. One of the best was the GS-5734, which is now known as remdesivir. “I’d like to call him a Destroyer,” said Denison.

Denison found that remdesivir was just what they were looking for: a drug that sneaks into the virus’s powerful system to protect ribonucleic acid, its genetic material. Remdesivir prematurely interrupted the development of the virus’s ribonucleic acid chains and ended it.

Remdesivir killed all known coronaviruses in Denison’s tests. Later, researchers at the University of North Carolina realized that the drug also killed viruses in infected animals.

That included not only the coronaviruses that cause the common cold, but also the causes of severe acute respiratory syndrome and respiratory syndrome in the Middle East, including a coronavirus that attacks mice.

But in real life, the drug was not successful, not only using it against hepatitis, but also against Ebola in Africa. The drug decayed without being approved for any use… until a new coronavirus emerged.

As SARS-CoV-2, the virus that causes COVID-19, began to become a pandemic, many scientists realized that remdesivir might be the best solution available. Animal experiments had already been done and had been safely tested in humans.

So doctors started giving it to their patients in studies where there were no control groups and even without them being part of the studies. Events fueled demand. Gilead sponsored some of these studies and provided the drug to doctors treating hundreds of patients for compassionate use, a legal exemption authorizing the use of any medication that is not approved for the treatment of patients.

However, none of this could demonstrate that the drug was useful to patients. The government trial, in which many patients were given a placebo, was needed to demonstrate that remdesivir appears to have a moderate effect.

Not everyone is convinced that remdesivir lives up to what it promises. In a China study published this week in the journal The Lancet, it was discovered that the medicine was not useful for very serious patients. In addition, many experts want to see data from the trial conducted by the National Institute for Allergy and Infectious Diseases; So far, there have only been statements by government officials about the results.

Despite these questions, Gilead has been increasing its production and now has 1.5 million vials available, which is enough for about 150,000 patients. Daniel O’Day, CEO of the company, said they will be provided to patients at no cost.

He didn’t mention how much Gilead would charge after formal approval, but remdesivir unlikely to be cheap, despite originating from government-sponsored research.

(c) The New York Times 2020


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