“At present clinical management includes infection prevention and control measures and supportive care, including supplementary oxygen and mechanical ventilatory support when indicated,” public health officials write. “An array of drugs approved for other indications as well as several investigational drugs are being studied in several hundred clinical trials that are underway across the globe.”
The CDC provides specific information on an investigational agent—remdesivir—currently in use in the United States. It was originally developed to treat Ebola and Marburg virus infections.
Remdesivir is an investigational IV drug with broad antiviral activity that inhibits viral replication through premature termination of RNA transcription and has in-vitro activity against SARS-CoV-2 and in-vitro and in-vivo activity against related betacoronaviruses.
A study published earlier this year in Proceedings of the National Academy of Science journal looked at its effectiveness in Middle East Respiratory Syndrome (MERS). The infection, caused by the MERS coronavirus (MERS-CoV), is similar to COVID-19 and severe respiratory disease with a high case-fatality rate.
In a National Institutes of Health study with a rhesus macaque model of MERS-CoV infection, remdesivir was determined to reduce the severity of disease, virus replication, and damage to the lungs when administered either before or after animals were infected with MERS-CoV. “Our data show that remdesivir is a promising antiviral treatment against MERS that could be considered for implementation in clinical trials. It may also have utility for related coronaviruses such as the novel coronavirus 2019-nCoV emerging from Wuhan, China,” the authors write.
The CDC advises that healthcare professionals have several options for obtaining remdesivir for treatment of hospitalized patients with COVID-19 and pneumonia in the United States:
• A National Institutes of Health (NIH)-sponsored adaptive double-blinded, placebo-controlled trial of remdesivir versus placebo in COVID-19 patients with pneumonia and hypoxia is enrolling nonpregnant adults with oxygen saturation of ≤94% on room air or requiring supplemental oxygen or mechanical ventilation (https://clinicaltrials.gov/ct2/show/NCT04280705). Exclusion criteria include alanine aminotransaminase or aspartate aminotransaminase levels >5 times the upper limit of normal, stage 4 severe chronic kidney disease, or a requirement for dialysis (i.e., estimated glomerular filtration rate (eGFR) <30);
• Two phase 3 randomized, open-label trials of remdesivir (5 days vs. 10 days vs. standard of care) are open to enrollment in adults with COVID-19, radiographic evidence of pneumonia and oxygen saturation of ≤94% on room air (severe disease https://clinicaltrials.gov/ct2/show/NCT04292899), or >94% on room air (moderate disease https://clinicaltrials.gov/ct2/show/NCT04292730). Exclusion criteria include alanine aminotransaminase or aspartate aminotransaminase levels >5 times the upper limit of normal, participation in another clinical trial of an experimental treatment for COVID-19, requirement for mechanical ventilation, or creatinine clearance <50 mL/min; and
• In areas without clinical trials, COVID-19 patients in the United States and other countries have been treated with remdesivir on an uncontrolled compassionate-use basis.
The manufacturer is currently transitioning the provision of emergency access to remdesivir from individual compassionate-use requests to an expanded-access program. Further information is available at: https://rdvcu.gilead.com.
Gilead, the company making the drug, suggests its “approach will both accelerate access to remdesivir for severely ill patients and enable the collection of data from all participating patients. These programs are currently under rapid development in conjunction with national regulatory authorities worldwide. More details on how to participate in the expanded access programs will be forthcoming.”
On its website, the company adds, “Thank you for your interest in emergency treatment with remdesivir. Remdesivir is an investigational agent and is not approved for use in any country. It has not been demonstrated to be safe or effective for any use. Enrollment in clinical trials remains the primary way to access remdesivir to generate critical data that inform the appropriate use of this investigational medicine.”
