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University of Nebraska Medical Center

RedHill’s antiviral, once tested for COVID, works in mice with Ebola

Fierce Pharma

RedHill Biopharma, in collaboration with the U.S. Army, announced Oct. 3 that twice-daily oral doses of the medication opaganib boosted survival from about six days in controls to 11 days in animals infected with the virus. In the group treated with the highest dose, 30% of the mice survived, compared to none of the controls. 

“Given the unmet medical need … these results with opaganib, an easy to distribute and administer oral small molecule drug, support its further investigation for use in treating Ebola,” study lead Rekha Panchal, Ph.D., principal investigator of therapeutics discovery at the U.S. Army Medical Research Institute of Infectious Diseases, said in a press release.

Opaganib is a host-directed antiviral, meaning it prevents a virus from hijacking a host’s cells for replication rather than destroying the pathogen directly. The drug mainly works by inhibiting the enzyme sphingosine kinase-2, or SPHK2, a key enzyme in a process called sphingolipid metabolism. Inhibiting sphingolipid metabolism with opaganib turns on processes that clear or repair infected cells, like autophagy and apoptosis.

That mechanism has prompted studies on opaganib in a range of indications from cancer to COVID. Under the name Yeliva, the drug received orphan-drug designation from the FDA in 2017 for the treatment of bile duct cancer and has been tested for that indication through phase 2a. It’s also in a phase 2 study for prostate cancer. In 2021, the drug flopped in a phase 2/3 test on patients with severe COVID-19 pneumonia, though RedHill said at the time it would continue investigating the drug in patients who were earlier in the course of their disease.

In February 2023, opaganib was selected for investigation by the National Institutes of Health and the Radiation and Nuclear Countermeasures Program as a potential treatment for acute radiation syndrome. The move came on the back of preclinical studies in mice suggesting it could prevent damage from ionizing radiation.

If the drug were to show efficacy against Ebola in humans, it would be only the third to do so. The two FDA-approved treatments for the virus both rely on antibodies that prevent it from entering the host’s cells and must be given by IV.

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