Story by Darnell Gardner
FORT BELVOIR, Va. - The COVID pandemic took the world by surprise. Researchers were left scrambling to devise a way to best mitigate the negative impact this disease has on global health. However, at the Defense Threat Reduction Agency (DTRA) it is common to operate in the “what if” space when it comes to potential biological threats. In fact, DTRA investments in technologies that detect, mitigate, or neutralize chemical and biological threats to the military and the nation date back more than 20 years.
“In late 2019, DTRA started a new program called Discovery of Medical Countermeasures Against Novel Entities (DOMANE) to address novel and emerging threats,” stated Dr. David Hone, Chief Scientist within the Vaccines and Therapeutics Division at DTRA. “Based on previous work, we decided DOMANE would not only focus on FDA-approved drugs but also combination therapeutics, as we believe that no single drug will be completely effective in treating new diseases. COVID-19 has provided us an opportunity to test our hypotheses using DOMANE.”
DOMANE provides rapid decision-making capabilities to identify FDA-approved drugs that will most likely be effective therapeutics for COVID-19. Repurposing candidate drugs from a pool about 7,500 FDA-approved drugs to advance an effective COVID-19 therapeutic allows for a more rapid response in developing a therapeutic regimen. The end-result is a response that modifies COVID-19 in treated patients and promotes a speedy recovery.
Veklury®, which is more commonly referred to as Remdesivir, is a ribonuclease inhibitor developed by Gilead Sciences. It delivers broad-spectrum antiviral activity and has proven to be a modestly effective therapeutic for the treatment of COVID-19. Originally developed as an Ebola Zaire countermeasure, this DTRA-funded inhibitor transitioned for more advanced testing due to promising pre-clinical trials. Remdesivir inhibits viral replication in a wide variety of pathogens and was one of the first therapeutics identified in the Defense Department for repurposing to treat COVID-19. In the summer of 2020, Remdesivir received authorization for emergency use only in COVID-19 patients with continued FDA oversight.
To complement the modest therapeutic effect of Remdesivir, DOMANE also identified Famotidine, a COVID-19 disease modifier from Johnson & Johnson; Pfizer’s Celecoxib, an anti-inflammatory product; and Merck’s Mectizan®, Ivermectin, an antiviral for clinical trials. To learn whether a combination of these FDA-approved drugs is more efficacious than current treatments, DTRA partnered with Quantum Leap Healthcare to conduct a clinical trial. This volunteer trial will evaluate drug combinations in COVID-19 patients who are having difficulty breathing.
DTRA also collaborated with Leidos to develop a new clinical trial prototype to evaluate new drug combinations in two clinical studies: one in COVID-19 patients who have symptoms but are still breathing without assistance and another in COVID-19 that are not displaying any symptoms.
“We believe that the evaluation of additional repurposed drugs in clinical trials will find a successful treatment option and will pave the road toward FDA-approval of a greatly improved therapeutic treatment for COVID-19 patients,” said Hone.
DTRA is committed to supporting global health biosecurity efforts through continued vaccine and therapeutic discovery actions to treat COVID-19, as well as the next biological threat the nation faces.