Remdesivir at Forefront of Battle Against COVID-19

Pill bottles of remdisivir

Remdesivir has emerged as a promising therapeutic candidate for the treatment of COVID-19 due to its ability to inhibit pathogenic animal and human coronaviruses, including severe acute respiratory syndrome 2 (SARS-CoV-2) and Middle East Respiratory Syndrome coronavirus (SARS-CoV-1).

In mid-March, Brigham and Women’s Hospital became one of multiple sites for two open-label, randomized, phase 3 clinical trials to evaluate the safety and efficacy of remdesivir among hospitalized adults with COVID-19. Led by Francisco Marty, MD, of the Brigham’s Division of Infectious Diseases, these two SIMPLE trials were sponsored by Gilead Sciences and closed to enrollment on May 29.

“When the COVID-19 pandemic was just beginning, I wanted to get in a position to help meaningfully, not just be on the defensive,” says Dr. Marty. “Our team at the Brigham had conducted clinical trials during the swine flu pandemic, so we had the relevant experience to potentially contribute to this crisis in a productive way.”

Five-Day Duration of Remdesivir Just as Effective as 10-Day

The first SIMPLE trial evaluated the safety and efficacy of both a five-day and a 10-day dosing duration of remdesivir, in addition to standard of care, for 400 patients with severe manifestations of COVID-19. The primary outcome was an improvement in clinical status by day 14 after enrollment. This clinical improvement was defined as being off oxygen and discharged from the hospital.

In a paper in the New England Journal of Medicine, co-authored by Dr. Marty, researchers described results of this remdesivir trial. They found that there was no significant difference in efficacy between the five-day and 10-day course of intravenous remdesivir treatment in patients who didn’t require mechanical ventilation.

“This trial should be analyzed and interpreted in the context of the double-blind, placebo-controlled study run by the National Institute of Allergy and Infectious Diseases (NIAID),” says Dr. Marty. “This NIAID trial, known as ACCT-1, demonstrated a faster time to clinical recovery in patients with severe COVID-19 who received remdesivir compared with those who received placebo (11 vs. 15 days, p<0.001).”

The second SIMPLE study evaluated the safety and efficacy of a five-day and a 10-day dosing duration of remdesivir in addition to standard of care for 600 patients with moderate manifestations of COVID-19, compared with standard of care alone. The primary outcome of this trial was an improvement in clinical status by day 11 after enrollment.

On June 1, Gilead announced topline results that five days of remdesivir treatment led to significantly greater clinical improvement versus treatment with standard of care alone in patients with moderate COVID-19. Specifically, patients who received remdesivir for five days were 65 percent more likely to have clinical improvement on a seven-point scale, where 1 was death and 7 was “not hospitalized,” at the end of 11 days. Patients with moderate COVID-19 who received remdesivir for 10 days were 31 percent more likely to have improved on the seven-point scale, but that difference was not statistically significant.

“Understanding the optimal length of treatment with remdesivir is a key question as we think about how best to care for our patients,” says Dr. Marty. “This work suggests that, for many patients, a shorter course of treatment may be just as effective, which could reduce hospital stays and potential adverse events, and extend the limited supply of remdesivir available during this first phase of the pandemic.”

Doing Meaningful Work in a Global Crisis

Under normal conditions, it can take two to three months to launch clinical trials like these at the Brigham. A number of things need to be put into place, including ethics review and approval, contract negotiations and research team trainings.

“Because of the focused and coordinated effort of the hospital’s administration, institutional review board and clinician teams, the Brigham launched the remdesivir trials in less than one week. Two months after launching, we had enrolled over 200 patients in our trials, more than any other center in New England,” says Dr. Marty.

Moreover, these clinical trials wouldn’t have been possible at the Brigham without the support of seasoned physicians and volunteering residents and fellows. They include: Jessica Little, MD, Cameron Nutt, MD, Luisa Paredes Acosta, MD, Aaron Richterman, MD and Mathias Lichterfeld, MD, PhD.

“During the trials, clinicians and patients alike started to notice that remdesivir was working and this generated a lot of hope,” says Dr. Marty. “Patients started getting better faster with remdesivir and there was a sense of optimism even before the results came out. We realized we were doing something meaningful during this pandemic.”  

Remdesivir: An Important Therapeutic Tool Against COVID-19

Outside of Japan, where remdesivir is approved as a treatment for patients infected with SARS-CoV-2, remdesivir is still an investigational drug. The FDA granted remdesivir an Emergency Use Authorization (EUA) for the treatment of hospitalized patients with severe COVID-19. This authorization is temporary and doesn’t take the place of the formal new drug application submission, review and approval process.

“Before we can hope for remdesivir’s FDA approval, we still need to wait for the final results of the SIMPLE trials that should be released in the next month,” says Dr. Marty. “We also need to see the final report of NIAID’s clinical trial, which should also come out later this month.”

In the meantime, Dr. Marty is encouraged to have a therapeutic tool that may reduce the harm caused by COVID-19. He aims to study remdesivir further, perhaps administering it earlier in the disease process, and hopes for a near future where he can prescribe the drug in an outpatient setting.

“Remdesivir may become a very useful therapeutic tool in the fight against COVID-19,” says Dr. Marty. “But it isn’t the whole answer. We still need a vaccine. And so, I will continue my clinical work while cheering on my colleagues who are working on the longer-term solution of vaccine development.”