Sanction of new antiviral drug brings hope and confusion

Anna Kuchment, Tribune News Service

As Raymond Schinazi watched Dr. Anthony Fauci reveal data from a highly anticipated clinical trial late last month, he knew he was witnessing history.

Here was Dr. Fauci, the top US infectious disease official, sitting with President Donald Trump at a White House meeting, revealing to reporters that a new drug had become the first to show effectiveness against COVID-19 from a scientifically rigorous clinical trial.

Yet the results had not been peer-reviewed and published, and they hadn’t been detailed to physicians in any written report. On May 1, based partly on the data shared by Dr. Fauci, the Food and Drug Administration granted emergency-use authorisation for the experimental antiviral drug, Remdesivir.

“It’s probably the first time that the FDA approved a drug with no data being presented — except minimally at a press conference in the Oval Office of the White House. Never have I seen that before in my life, and I’m 70 years old,” said Schinazi, an expert on antiviral drugs at Emory University.

He did not criticise the approval, however. “We live in desperate times,” he said. “We need something.”

The new treatment brings hope as well as confusion. While promising, the drug works for only some patients, has modest effects and must be delivered by IV in a hospital setting. So, researchers will have to keep working on new treatments. Many are on the horizon, including antiviral pills, as well as new formulations of Remdesivir that can be inhaled like asthma medications or injected like insulin. Researchers are also looking at drugs that can be given with Remdesivir to boost its effectiveness.

Meanwhile, even as doctors celebrated the arrival of Remdesivir, states and hospitals scrambled to secure supplies of the drug. Many expressed outrage at a seemingly haphazard process.

Steve Love, president and CEO of the Dallas-Fort Worth Hospital Council, which advocates for the region’s hospitals, was dismayed on Friday when he learned that Texas was not among the first dozen states to receive the government’s initial shipments of the drug.

“We want everyone to get their fair share, but we certainly need some in Texas,” said Love. “We have some of the largest metropolitan areas in the nation.” Over the last week, Dallas County has seen record numbers of people testing positive for COVID-19.

Adding to his frustration was a lack of clarity about how the government was making decisions about where and when to distribute the 607,000 vials of Remdesivir that pharmaceutical company Gilead had donated within the United States. (607,000 vials are enough to treat approximately 78,000 hospitalized COVID-19 patients.) He spent Friday calling legislators in an effort to find out when North Texas would get its turn. He was told that the U.S. Department of Health and Human Services, or HHS, was still working on its distribution plan. Meanwhile, at a news briefing on Friday, White House Press Secretary Kayleigh McEnany said Dr. Deborah Birx, the coronavirus task force response coordinator, would be in charge of drug distribution.

Outfoxing the virus: Like other drugs in its class, Remdesivir works by tricking viruses into incorporating the drug into their genomes. The synthetic building blocks stop the viruses from replicating.

In the past, that strategy has failed with coronaviruses, said Andrea Pruijssers, a researcher at Vanderbilt University Medical Center who studies antiviral drugs. Unlike other viruses that contain single strands of genetic material called RNA, coronaviruses have a proofreading mechanism that nimbly detects and fixes errors, she said.

In ways that scientists have yet to fully understand, Remdesivir slips into the virus’s RNA undetected, said Pruijssers.

Preliminary data from the NIH clinical trial, which followed 1,063 hospitalised patients, showed that those who received Remdesivir recovered in 11 days compared with 15 days for those who received placebo. The data, shared in a press release, also suggests that Remdesivir lowers mortality rates, though the reduction in the study was not statistically significant.

“The antiviral is important, but it’s not enough,” said Dr. Mamta Jain, a physician at UT Southwestern who is investigating Remdesivir’s effectiveness as part of two trials sponsored by Gilead. She said she did not expect her access to the drug to be affected by the emergency use authorisation and said she is continuing to enroll five or six patients a day. Pruijssers and her colleagues have researched another antiviral that works in a similar way to Remdesivir but can be taken as a pill. Developed at Emory University and licensed to the Florida-based pharmaceutical company Ridgeback Biotherapeutics, the drug recently entered early-stage clinical trials in the United Kingdom. Still lacking a brand identity, it goes by the name EIDD-2801.

Gilead’s CEO said in a recent interview on CBS News’ Face the Nation that the company was looking into subcutaneous formulations that could be injected into the skin like insulin and an inhaled version that could be given outside hospital settings. Pruijssers and her team are looking to screen many more drugs for effectiveness, some of which could be combined with each other for greater potency and to help prevent the development of drug resistance. “We don’t just want to treat the current pandemic. We want to treat whatever is next, because coronaviruses are not done causing pandemics,” said Pruijssers.

Experts say that Remdesivir likely works best at earlier stages of the illness, when the SARS-CoV-2 virus is replicating rapidly.

“For people who are later on in the course of their illness, we still need to identify other therapies that are helpful to them,” said Dr. James Cutrell, associate professor of medicine in the division of infectious diseases and geographic medicine at UT Southwestern.

Those potential therapies include anti-inflammatory drugs used for arthritis and other autoimmune diseases, which help tamp down the patient’s immune response. COVID-19 patients often end up on ventilators not because of the virus itself but because their immune systems overreact and inflame the lungs.

On Friday, the National Institutes of Health announced that a second phase of its Remdesivir trial would combine the drug with an anti-inflammatory licensed to Eli Lilly and Company called baricitinib, which is FDA-approved to treat rheumatoid arthritis.

“This could be our salvation, if indeed they work together nicely,” said Schinazi of Emory University, who has studied the use of baricitinib in patients with viral infections. Unlike other anti-inflammatory drugs that target just one or two markers, baricitinib brings down nearly all of them, said Schinazi. Some experts have compared the COVID-19 pandemic with the early days of HIV. Dr. Steven Davis, an infectious disease physician at Baylor Scott & White Medical Center — Irving remembers treating AIDS patients in the 1980s and ‘90s when few treatments were available.

“I didn’t think after HIV and AIDS that I would ever see such a challenging disease present itself,” he said. He credits Remdesivir with helping save a young COVID-19 patient who had spent two weeks on a ventilator.

The arrival of Remdesivir also reminded physicians of the first drug to show effectiveness against HIV: the antiviral AZT. That drug prolonged life, but caused serious side-effects. Still, the scientific community was able to build on its success.

“Now we have drugs (for HIV) that are extremely safe and they help people live for 30-plus years,” said Dr. Jain. “So I think this is just the beginning.”