Small Molecule Drug Combination Shows Positive Effect Against Ebola

With approved Ebola vaccines and monoclonal antibody therapies available in Africa, a safe and effective treatment option is now the goal for researchers.

RedHill Biopharma Ltd. today announced that its two novel, oral host-directed investigational drugs, opaganib and RHB-107 (upamostat), demonstrated robust synergistic effect when combined individually with Veklury®, significantly improving viral inhibition while maintaining cell viability in a new U.S. Army-funded and conducted Ebola virus disease in vitro study.

Jeffrey Kugelman, Ph.D., Major(P), U.S. Army MSC, Branch Chief Synthetic Biology & Surveillance, Molecular Biology Division, U.S. Army Medical Research Institute of Infectious Diseases, who led the bioinformatics analysis of the study, commented in a press release on December 20, 2023, "The results suggest that opaganib and upamostat may have potential or use in combination with direct antiviral agents, such as Veklury, to improve treatment outcome, increasing efficacy while maintaining safety."

Opaganib (ABC294640) is a proprietary investigational host-directed and potentially broad-acting drug and is a first-in-class, orally administered sphingosine kinase-2 selective inhibitor with anticancer, anti-inflammatory, and antiviral activity, targeting multiple potential diseases.

"Opaganib is believed to be the first host-directed molecule to show activity in Ebola virus disease, and these results add to a recent U.S. Army Ebola virus study in which opaganib delivered a statistically significant increase in mice survival time in vivo," added Reza Fathi, Ph.D., RedHill's SVP R&D. 

RHB-107 (upamostat) is a proprietary, first-in-class, once-daily orally administered investigational antiviral that targets human serine proteases in preparing the spike protein for viral entry into target cells. Because it is host-cell targeted, RHB-107 is expected to also be effective against emerging viral variants with mutations in the spike protein. In addition, RHB-107 inhibits several proteases targeting cancer and inflammatory gastrointestinal disease.

There are two types of Ebola causing outbreaks in Africa.

The initial Zaire Ebolavirus disease outbreak was confirmed in 1976 in South Sudan and the Democratic Republic of Congo.

African countries have endured Zaire Ebolavirus outbreaks between 2014, 2016, 2018, and 2022. Over 29,000 people were infected, and more than 11,000 died.

Separately, there have been five Sudan Ebolavirus outbreaks. 

The World Health Organization issued new guidelines (August 2023) on Ebola infection prevention and control.