RedHill Biopharma Ltd. (Nasdaq: RDHL) has been awarded U.S. government funding through the Biomedical Advanced Research and Development Authority (BARDA) to advance the development of opaganib for the treatment of Ebola virus disease (EBOV). This collaboration aims to address the critical need for effective and easily deployable therapies against EBOV, which has a high mortality rate, with approximately half of those infected succumbing to the disease, according to the World Health Organization (WHO).
Opaganib is a novel, orally administered sphingosine kinase-2 (SPHK2) selective inhibitor with broad-acting antiviral and anti-inflammatory properties. It is currently under investigation for multiple indications, including oncology, viral infections, and inflammatory conditions. The recent BARDA funding will support the advancement of opaganib through the FDA Animal Rule pathway, which allows for the approval of drugs based on animal model efficacy studies when human clinical trials are not feasible or ethical.
Preclinical Evidence
Recent studies funded by the U.S. Army have demonstrated opaganib's potential in combating EBOV. In an in vivo study conducted by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), opaganib, when administered at 150 mg/kg twice daily (BID), led to a statistically significant increase in survival time in EBOV-infected animals. This marks opaganib as the first host-directed molecule to exhibit activity against EBOV in vivo.
Furthermore, an in vitro study, also funded by the U.S. Army, revealed that opaganib, in combination with remdesivir, exhibited a synergistic effect against EBOV, significantly improving potency while maintaining cell viability.
Addressing Unmet Needs in Ebola Treatment
Guy Goldberg, RedHill's Chief Business Officer, emphasized the urgent need for new Ebola therapies, particularly host-directed, small molecule treatments that are easy to distribute and administer. "EBOV is deadly, killing, on average, half of all those who contract it... there is an urgent medical need for additional effective and easy to distribute and administer EBOV therapies," Goldberg stated. He also noted the logistical challenges in managing Ebola outbreaks and the potential of opaganib to overcome these challenges due to its oral administration, extended shelf-life, and ease of transport.
Currently, the FDA has approved only two treatments for EBOV: Inmazeb™ (a combination of three monoclonal antibodies) and Ebanga™ (a single monoclonal antibody). Both are intravenously administered, which poses logistical challenges in outbreak settings with limited healthcare infrastructure. Opaganib, as an orally available small molecule, offers a potential advantage in terms of storage, distribution, and administration, especially in resource-limited settings.
Opaganib's Mechanism of Action
Opaganib's host-directed mechanism of action involves the inhibition of multiple pathways, induction of autophagy and apoptosis, and disruption of viral replication through the simultaneous inhibition of three sphingolipid-metabolizing enzymes in human cells (SPHK2, DES1, and GCS). This approach is believed to contribute to its mutation-resistant antiviral activity, making it less susceptible to viral escape mechanisms.
Broader Applications and Ongoing Development
In addition to its potential in treating Ebola, opaganib is also being developed for other indications, including COVID-19, acute respiratory distress syndrome (ARDS), and radiological and chemical protection or mitigation. It has also demonstrated antiviral activity against SARS-CoV-2 and other viruses, such as Influenza A.
RedHill Biopharma's collaboration with BARDA represents a significant step forward in the development of opaganib as a medical countermeasure against Ebola. The funding will support further research and development efforts, bringing opaganib closer to potential approval and addressing a critical unmet need in global health security.
