Claiming more than 11,000 lives, the 2014 Ebola outbreak in West Africa was the largest in history. A relatively new "emerging" virus, Ebola currently has no approved treatment and, depending on virus strain and kind of healthcare available, it kills 40 to 80 percent of those infected. Gilead scientists are working to help change that with an investigational molecule called GS-5734.
In 2014, Gilead began a collaboration with the Centers for Disease Control and Prevention and the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID) to see whether several molecules originally explored as potential treatments for other viruses including hepatitis C, respiratory syncytial virus, and influenza might also be active against emerging viruses such as Ebola. The collaboration identified GS-5734, a nucleotide prodrug that is processed in the body to rapidly release active drug into cells.
In April 2015, scientists at USAMRIID began to test an intravenous formulation of GS-5734 in an animal model to determine the optimal dose and time of treatment initiation. Six groups of six animals infected with Ebola virus received once-daily intravenous dosing of placebo or GS-5734 at 3 to 10 mg/kg/day for 12 days initiated on Day 0 to 3 post infection. Results from this preclinical study showed 100 percent survival in 12 animals treated with GS-5734 three days after exposure to the virus. GS-5734 has also been given to two patients, one in the United Kingdom in October 2015 and one in Guinea the following month, through a compassionate use request. Two Phase 1 human trials are now underway in healthy adult volunteers.
“GS-5734 is thought to work by blocking a key enzyme the virus needs for replication,” said Tomas Cihlar, Gilead’s vice president, Biology. “Based on animal studies, we believe that the compound is able to penetrate the organs and tissues throughout the body where Ebola replicates.”
Although efforts are early, Gilead is working to advance GS-5734.
GS-5734 is an investigational compound that has not been proven safe and effective for the treatment of Ebola; additionally, its clinical effect in the compassionate use request cases cannot be determined.