There are a variety of medications being studied for the COVID-19, and the possible treatment landscape is rapidly evolving.
There are no FDA-approved medications for the treatment of COVID-19. Currently, medical management consists of infection prevention and supportive care, which includes supplemental oxygen and mechanical ventilator support when indicated. Based on a search of ClinicalTrials.gov, there are at least 181 clinical trials being conducted as of April 14, 2020, both studies at the recruiting stage and those that have already begun. The scientific community is coming together to find safe and effective treatment options to combat COVID-19, which include existing and novel drugs.
Remdesivir is an intravenous (IV) drug with broad antiviral activity (for example, SARS virus and Middle East respiratory syndrome) that has been used for the treatment of Ebola virus, and it works by inhibiting viral replication through premature termination of RNA transcription. Additionally, remdesivir appears to have a favorable safety profile based on its having been used to treat approximately 500 individuals, including healthy volunteers and those with acute Ebola virus infection. Remdesivir is being studied by Gilead Sciences for the treatment of COVID-19 and evidence suggests that it is currently one of the most promising investigational drugs.
On April 29, Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), announced positive interim results of an NIAID-sponsored study of remdesivir. Fauci said the time to recovery was shorter for COVID-19 patients randomized to the remdesivir arm of the study than the patients in the placebo arm (11 days vs. 15 days) and that difference was statistically significant. However, on the same day, results published in Lancet from a randomized, placebo-controlled trial of remdesivir conducted in the Hubei province in China showed no association between treatment with the antiviral and a difference in time to recovery. Results of a cohort study were published in the New England Journal of Medicine on April 10, 2020, examining compassionate use of remdesivir in 61 patients hospitalized with COVID-19 with an oxygen saturation of 94% or less while breathing ambient air or who required oxygen support.
Patients received a 10-day treatment of remdesivir 200 milligrams (mg) IV on day 1 followed by 100 mg for the remaining 9 days of therapy. Fifty-three patients had data analyzed (seven lacked posttreatment data, one had a dosing error) and clinical improvement was seen in 68% of patients. A total of 32 patients (60%) reported adverse events (AEs) during follow-up. The most common AEs were increased hepatic enzymes, diarrhea, rash, renal impairment and hypotension. Twelve patients (23%) experienced serious AEs, including multiple organ dysfunction syndrome, septic shock, acute kidney injury and hypotension, with most occurring in those receiving invasive ventilation. The results are promising, but more robust studies are needed to determine the safety and efficacy of remdesivir for patients with COVID-19. Study limitations included the drug not being randomized and lacking a control, missing data, and a short follow-up duration.
There are currently two phase 3 randomized clinical trials, known as the SIMPLE studies, for patients with severe COVID-19 symptoms (NCT04292899) and for those with moderate symptoms (NCT04292730). Gilead released topline results from the SIMPLE trial studying patients with severe COVID-19, which demonstrated similar improvement with the five- and 10-day treatment regimens of remdesivir. Time to improvement for 50% of study participants was 10 days in the five-day treatment group, and more than half of patients in both groups were discharged from the hospital by 14 days. Results are expected by May 2020 for the study evaluating patients with moderate COVID-19. Since January 25, 2020, as part of individual compassionate use protocols, Gilead has been providing emergency access to remdesivir for over 1,800 qualifying patients with severe COVID-19 symptoms who are unable to enroll in ongoing clinical trials. The company is currently working on transitioning to expanded access of remdesivir for patients with severe symptoms and will collect and analyze treatment data.