Dr Anthony Fauci, one of the leading experts on the White House coronavirus task force, said on Apr. 29, that there is reason to be optimistic about the preliminary results of a worldwide clinical trial of the experimental drug, remdesivir, as a potential treatment for people who are hospitalized with severe COVID-19 infection.

 

Norwood News reported in April that one of the locations for this international remdesivir drug trial was the Moses Campus of Montefiore Health System where clinical trials began in March, in conjunction with the Albert Einstein College of Medicine.

 

On Friday, May 1, the Trump administration announced emergency use authorization of remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease. The issuance of an emergency use authorization is different from FDA approval.

 

The emergency use authorization allows for remdesivir to be distributed in the U.S. and administered intravenously by health care providers, as appropriate, to treat suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.

 

Severe disease is defined as patients with low blood oxygen levels or needing oxygen therapy or more intensive breathing support such as a mechanical ventilator.

 

In its statement announcing the approval, the FDA wrote, “Given there are no adequate, approved, or available alternative treatments [for COVID-19], the known and potential benefits to treat this serious or life-threatening virus currently outweigh the known and potential risks of the drug’s use,” the referenced drug being remdesivir.

 

The emergency use authorization also requires that fact sheets that provide important information about using remdesivir in treating COVID-19 be made available to health care providers and patients, including dosing instructions, potential side effects and drug interactions.

 

Possible side effects of remdesivir include: increased levels of liver enzymes, which may be a sign of inflammation or damage to cells in the liver; and infusion-related reactions, which may include low blood pressure, nausea, vomiting, sweating, and shivering.

 

The ongoing Bronx-based trial is a randomized, double-blinded, and placebo-controlled program. A double-blinded trial means the patients and their doctors do not know which drug or treatment is being given to the patients.

 

Placebo-controlled studies are a way of testing a medical therapy in which, in addition to a group of subjects who receive the treatment to be evaluated (in this case remdesivir), a separate control group receive a “placebo” treatment which is specifically designed to have no real effect.

 

The trial is being led by principal investigator Barry Zingman, M.D., professor of medicine at Einstein and clinical director, infectious diseases, in the Moses division of Montefiore Health System.

 

Preliminary results of the international trials indicate that patients who received remdesivir had a 31 percent faster time to recovery than those who received placebo. Specifically, the median time to recovery was 11 days for patients treated with remdesivir, compared with 15 days for those who received placebo.

 

Results also suggested a survival benefit, with a lower mortality rate of 8 percent for the group receiving remdesivir versus 11.6 percent for the placebo group.

 

Fauci spoke to reporters from the Oval Office alongside President Donald Trump and other White House officials about the preliminary results on Apr. 29. “Although a 31 percent improvement doesn’t seem like a knockout 100 percent, it is a very important proof of concept,” he said.

 

“What it has proven is that a drug can block this virus, and I’ll give you an example in a moment of why we think, looking forward, this is looking very optimistic.”

 

Fauci said that the investigators running the international trials contacted him on Apr. 27 to say that remdesivir had a clear cut, significant positive effect in diminishing the time to recovery for patients.

 

“The primary endpoint was the time to recovery, namely the ability to be discharged,” Fauci said. “When you have a study like this, we have a data and safety monitoring board, which looks at the data, and they are independent, so there’s no prejudice on the part of the investigators because they’re doing the trial, or [because] the drug is from a certain company.”

 

Candidates for the Bronx-based trial, who had serious lung complications as a result of COVID-19, were selected in March at which time they provided their consent to participate in the experimental treatment.

 

The trial was “adaptive,” meaning it could be modified to include other investigative treatments. People in the treatment group received 200 mg of remdesivir intravenously on the first day of their enrollment in the study and another 100 mg each day for the duration of hospitalization, for up to 10 days in total. The placebo group received an equal volume of a solution that resembles remdesivir but contained inactive ingredients.

 

A representative from Montefiore said on May 1 that while they don’t have any specific results of the Bronx-based trial that they can share with the press at this time, “the drug has been well-tolerated” by patients.

 

The various trials still taking place across the world started on different dates, as additional locations joined the global study.

 

The Montefiore representative said that 91 patients participated in the phase I trial at Montefiore and Einstein and that “many people have done great,” but that their research is still blinded, so they’re unable to get into specifics. The representative added that data is still being analyzed, and that they are going to be moving forward with phase 2 of the trial.

 

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, released a statement on Apr. 27 in which it, too, referenced the preliminary results of the international trials. “The clinical trials of remdesivir show that it accelerates recovery for advanced COVID-19 patients,” the statement read in part.

 

“Hospitalized patients with advanced COVID-19 and lung involvement who received remdesivir recovered faster than similar patients who received placebo, according to a preliminary data analysis from a randomized, controlled trial involving 1,063 patients,” NIAID’s statement continued.

 

The trial program, known in the U.S., as the Adaptive COVID-19 Treatment Trial (ACTT) was the first clinical trial launched in the United States to evaluate an experimental treatment for COVID-19. The trial closed to new enrollments on Apr. 19.

 

Trials using remdesivir had already started at other locations around the globe in February, in the hope that the drug would help patients with serious COVID-19 complications.

 

The Montefiore site in the Bronx was the first such site to open in New York State as part of the international multi-center effort to fight the deadly disease. A total of 68 sites ultimately joined the study—47 in the United States and 21 in countries in Europe and Asia.

 

The first trial participant in the ACTT trial was an American who was repatriated after being quarantined on the Diamond Princess cruise ship that docked in Yokohama, Japan, and volunteered to participate in the study at the first study site, the University of Nebraska Medical Center/Nebraska Medicine, in February 2020.

 

The independent data and safety monitoring board (DSMB), mentioned by Fauci in his remarks to the press, and which oversees the trial, met on Apr. 27 to review the data, and share interim analysis with the study team.

 

Based upon their review of the data, they noted that remdesivir was better than placebo from the perspective of the primary endpoint, time to recovery, a metric often used in influenza trials. Recovery in this study was defined as being well enough for hospital discharge or returning to normal activity level.

 

In the statement from NIAID, the group also advised that more detailed information about the trial results, including more comprehensive data, will be available in a forthcoming report.

 

As part of the U.S. Food and Drug Administration’s commitment to expediting the development and availability of potential COVID-19 treatments, the agency has been engaged in sustained and ongoing discussions with Gilead Sciences, which produces remdesivir, to make it available to patients as quickly as possible, as appropriate.

 

The urgent need to find a treatment for the coronavirus disease which, to date, has resulted in, at least, 110,000 deaths globally according to the World Health Organization, has animated scientists and researchers across the globe into a global race to find a cure.

 

On Apr. 29, The Lancet, an independent, international, weekly, general medical journal founded in 1823, published an article citing the results of a randomized, double-blinded, placebo-controlled, multi-centre trial funded by The Chinese Academy of Medical Sciences Emergency Project of COVID-19, in which the authors appeared more cautious about the effectiveness of remdesivir in treating the coronavirus.

 

Overall, based on the study, the authors found that remdesivir was not associated with statistically significant clinical benefits. However, they said that larger studies were needed.

 

Meanwhile, Fauci said that scientists would have normally waited several more days before releasing the results of the global trials to ensure further accuracy. “Some of the numbers may change a little but the conclusion will not change,” he said.

 

“The reason why we’re making the announcement now is something that I believe people don’t fully appreciate,” Fauci said. “Whenever you have clear cut evidence that a drug works, you have an ethical obligation to immediately let the people who are in the placebo group know so that they could have access, and all of the other trials that are taking place now have a new standard of care.”

 

NIAID will provide an update on the plans for the ACTT trial moving forward.

 

*Editor’s Note: It should be noted that remdesivir is not currently FDA approved as a treatment for the coronavirus and this article refers only to the preliminary results of a supervised clinical trial of the drug, as well as the subsequent issuance of an emergency use authorization, which is different from standard FDA approval. Members of the public are reminded to always consult with a trusted physician or healthcare provider in relation to health-related matters.