What is remdesivir, the drug that worked in two coronavirus patients and is being studied at full speed in five trials around the world


From the time the patient was confirmed to be ill with the new coronavirus until the compassionate use of remdesivir was approved, it took only 36 hours, she told Science George Thompson, physician at the University of California at Davis.

“It is too little for the emergency approval of an investigational drug,” he clarified.

“What was the patient’s condition like?”

“We thought he was going to die.”

This was the first identified case of community spread in the United States: someone who had tested positive for SARS-CoV-2 and had not traveled to an infected area abroad or had contact with a confirmed case or with symptom.

“The day after the drug was applied, it improved consistently,” Thompson continued. “I can’t prove it’s related. I wish we could have done serial blood tests, but we couldn’t because of lack of resources.” They had just 20 kits. lab for the entire county of Sacramento, which is the capital of California. And the patients kept coming. Now a clinical trial at the University of Nebraska is trying to determine if that antiviral, originally developed against Ebola, could be one of the keys to stop the pandemic.

Why, if it was used against Ebola, is it not approved yet? What does remdesivir have that makes it a good candidate but not so much that it has already been marketed?

“A decade ago, a group of chemists came up with a compound they called 3a simply and which, in laboratory experiments, killed several different viruses,” Stat said. “One was a type of coronavirus.” Remdesivir is a descendant of that molecule, and it received a more complex name, GS-5734, in the company that develops it, Gilead, the same that with the Truvada combination (emtricitabine and tenofovir disoproxil) presented the first therapy that can prevent contagion. HIV, known as PrEP.

Remdesivir started as a treatment for Ebola and the Marburg virus, but it also proved useful – its mechanism is to interfere with the replication of the invading microorganism – against the respiratory syncytial virus, Junin virus, Lassa fever virus, and some coronaviruses such as those causing Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). Its use against the Nipah, Hendra and Covid-19 viruses is currently being studied.

“Born as a candidate for broad-spectrum antiviral, he was thrown into a series of viruses to see where he would adhere,” Andrew Joseph synthesized in his article for Stat. “He went from the Gilead laboratories to the academic centers, moved by the taxpayers’ money and that of the company. It continued to show evidence of potential in cells and animals infected with other coronaviruses, but none of them then caused a sustained global crisis. ”

Now, however, Remdesivir gained prominence.

China was interested first, of course; in the United States, he entered the compassionate use program and perhaps saved the life of the Sacramento woman. The results of the clinical trial in Nebraska and 19 other locations are awaited with anxiety, of which four are already active in Georgia and Washington State. “At the moment there are no approved therapies for coronavirus infections, and remdesivir is the most advanced in the development process,” Stat recalled. Bruce Aylward of the World Health Organization said last month: “Right now there is only one medicine that we think can be truly effective. And it is remdesivir ”.

According to the EMCrit Project, Gilead’s drug “could be an excellent antiviral”; The independent scientists site cited a study from Timothy Sheahan, an epidemiologist at the University of North Carolina at Chapel Hill, on MERS, both in vitro and in animals, this year. The study showed that the combination of remdesivir and interferon “has superior antiviral activity than the combination of lopinavir, ritonavir and interferon,” which was the one evaluated by Saudi Arabia. “In mice, both prophylactic and therapeutic remdesivir improve lung function and reduce viral load and severe pathology in the lungs.”

However, Gilead Vice President of Virology Tomas Cihlar reminded Stat, “Drug discovery and development is often a very long and tedious process, and we can have many failures on the way to an approved product.” Remdesivir already stumbled when animal studies demonstrated its strength against Ebola, but two out of four human clinical trials resulted in “less impactful survival benefits.”

Cihlar added: “It would be wonderful if it worked. But you have to try it. “

The other COVID-19 case in which the use of remdesivir appears to have been crucial occurred in January at the Providence Regional Medical Center in Everett, Washington state. A 35-year-old man, who had just visited Wuhan, presented with a fever and cough. It wasn’t bad, but the doctors were already following the development of the crisis in China. “That made us deal with the worsening of this disease,” said George Diaz, chief of infectious diseases at the center.

In a few days the man began to need oxygen. A plaque revealed that her cold was actually pneumonia.

Díaz informed the Center for Disease Control and Prevention (CDC), where they suggested the use of an experimental drug. “Treatment with intravenous remdesivir started the night of the 7th and no adverse events were observed,” the medical team wrote in the New England Journal of Medicine (NEJM, for its acronym in English). The next day the man began to improve.

The CDC was aware that, after bad news about its effectiveness against Ebola, the drug from Gilead had caught the attention of Chinese doctors at the forefront of the epidemic. When they released the SARS-CoV-2 genome, the lab looked at the sector that contained the keys to the virus’s mode of reproduction: they found it to be almost identical to the SARS version. “It was a forceful signal,” Cihlar recalled to Stat.

However, success in these two cases is not the basis for recognizing a treatment. For that clinical trials are necessary. It is necessary to know, for example, whether it is better to resort to the drug at an early stage of infection, when a person’s virus levels are lower. Also if it can generate complications, such as putting the immune system on excessive alert, so that it begins to act against the body itself.

“There are currently five clinical trials of remdesivir for COVID-19: two are being conducted by Chinese scientists, one on severe infections and one on mild and moderate infections; [en los Estados Unidos], one is sponsored by the National Institute of Health (NIH); and the other two are in the hands of Gilead in different countries that have a large number of cases, and they analyze the different degrees of severity of the disease and the dosage regimens, ”summarized Stat.

“For people like me, people of basic science, there is often no direct implication between what we do and improving human health,” Sheahan of UNC, who had studied this drug against MERS, told the health publication. “It is hard to imagine that the work we do in a laboratory in North Carolina could save lives around the world. It is incredibly rewarding, but it is surprising and unusual for someone like me. ”

If the drug is successful in trials, it would in principle be used mostly in patients with more severe symptoms or hospitalized, according to experts: between 15% and 20% of cases. But some of the cases tested in China included patients whose symptoms had started up to 12 days earlier, which may be too late. For now the moment, as the right dose, are part of the analysis.

Other issues of importance will be the price of the medication, about which Gilead did not want to expand. One issue that leads to another in the commercial chain: the availability of supplies to manufacture the drug. Even if it were only recommended to people hospitalized and with severe infections, it would speak of thousands of patients who urgently need doses. Gilead CEO Daniel O’Day said the company “is already engaging the supply and manufacturing chain, in the event of a success” in the trials. He has also started talking to his partners, as he may need production help: “Right now, the demand we may have is really unknown.”

While remdesivir is ahead, there are also other therapeutic responses under study to tackle the COVID-19 pandemic, not to mention vaccine-seeking projects. There is a team of virologists from UNC-Vanderbilt and another from Emory working on three compounds, for now identified as NHC, EIDD-2801 and EIDD-1931. Also the company Regeneron, which has a successful antiviral against Ebola, is working on an alternative. Finally, some experts have proposed that the antibodies generated by survivors of this coronavirus be used.