Remdesivir

Remdesivir (GS-5734) is an investigational broad-spectrum anti-viral drug under development by Gilead Sciences of Foster City, California. It is currently not approved for treatment of any disease in the United States and is not commercially marketed, but has been distributed for clinical research trials and under "compassionate use" guidelines for experimental treatment.

Remdesivir is one of thousands of molecules compiled into a "compound library" by Gilead, which was engaged in seeking drug treatments for hepatitis C and respiratory syncytial virus. It was identified by researchers at the U.S. Centers for Disease Control as a candidate for further investigation as a compound with the capability of interfering with self-replication in a broader range of viruses. GS-5734 was cultured into an intravenous drug which showed promise in studies led by Sina Bavari and Travis Warren of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). Those studies, notably, provided evidence that the compound was effective in combating infection from the Ebola virus in rhesus monkeys.

Gilead filed for investigational status for remdesivir in June 2015 and initiated the first human clinical trials that August, advancing manufacturing and distribution processes to facilitate that work. At the same time, under compassionate use protocols, remdesivir was used in treating a small number of individuals infected with Ebola in Africa. Further investigations by the National Institutes of Health identified more promising treatments for Ebola, however, and trials involving remdesivir were suspended.

Meanwhile Gilead began to work with researchers at the University of North Carolina and Vanderbilt University to study the effects of remdesivir in in vitro and mouse models infected with the SARS-associated coronavirus (SARS-CoV) and the the MERS-coronavirus (MERS-CoV). In 2014 the National Institute of Allergy and Infectious Diseases (NIAID) awarded a five-year grant for the creation of an Antiviral Drug Discovery and Development Center (AD3C). The UAB School of Medicine was tapped to manage the administration of the center while also partnering with Southern Research on compound screening and medical chemistry, specifically targeting influenza. UAB's Richard Whitley was named principal investigator and program director for AD3C. Ghalib Alkhatib and James Noah led Southern Research's participation.

Within the Antiviral Drug Discovery and Development Center, UNC and Vanderbilt continued to focus on treatments for coronaviruses, which were identified as a potential major global threat. These studies, supported by Gilead, showed promising results for remdesivir in primates infected with MERS. Further trials involving human subjects could not be pursued due to low infection rates.

When the SARS-CoV-2 virus emerged in China in 2019, those preclinical results suggested that remdesivir could be a promising candidate for treatment of the fast-spreading COVID-19 disease. Gilead provided supplies and data to the Chinese Center for Disease Control and Prevention, as well as to its research partners in the United States. Numerous clinical trials were begun, including one at UAB Hospital. The NIAID initiated a global clinical trial program in late February 2020. Gilead began enrolling patients in its own Phase 3 clinical trials in March, while also supplying the compound to research institutions worldwide. The company also began preparing to manufacture and distribute remdesivir at large scale should it be approved as treatment for the pandemic disease.

References

• Carter, Kendra (March 19, 2014) "New antiviral drug discovery center established at UAB" UAB News
• Warren, Travis K., et al (March 2, 2016) "Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys." Nature. No. 531, pp 381–385
• Koplon, Savannah (February 7, 2020) "Investigational compound remdesivir, developed by UAB and NIH researchers, being used for treatment of novel coronavirus" UAB News
• "Development of Remdesivir" (2020) Gilead Sciences