RedHill Biopharma (NASDAQ: RDHL) has announced positive in vivo results that indicate opaganib combined with venetoclax reduces chronic lymphocytic leukemia (CLL) cells by half compared to controls—demonstrating opaganib’s potential as an add-on therapy to venetoclax in venetoclax-resistant CLL.
According to RedHill, opaganib has a safety and tolerability profile shown in more than 470 clinical trials/expanded access participants. It targets multiple oncology, virology, inflammation, medical countermeasures, diabetes and obesity indications, with several U.S. government partnerships, including Biomedical Advanced Research and Development Authority funding, in place.
In a statement, the study leader, Romina Gamberale, PhD, independent researcher at CONICET from the Institute of Experimental Medicine (IMEX, CONICET-National Academy of Medicine) in Buenos Aires, Argentina, commented, “Understanding mechanisms of resistance to targeted therapies such as the BCL-2 inhibitor venetoclax is essential to improve current treatment strategies and may provide key insights to personalize treatment for CLL patients. “Our previous ex vivo work has shown that sphingosine kinase 2 (SPHK2) is overexpressed in venetoclax-resistant CLL cells and that inhibiting SPHK2 may reduce T-cell-induced resistance and resensitize previously resistant cells. The results of this in vivo study in mice indicate that adding opaganib, a potent SPHK2 inhibitor, to venetoclax reduced CLL cell counts by 50% compared to controls, showing that opaganib may have a significant role to play in mitigating BCL-2 inhibitor resistance.”
Dr. Mark Levitt, CSO at RedHill, remarked, “Venetoclax is a key CLL therapy and finding ways to maintain its effectiveness, and to reduce the potential for resistance-related treatment failure, could represent a breakthrough in the ability to treat CLL patients. This promising data supports the hypothesis that opaganib, as a potent inhibitor of SPHK2, provides a potential route to maintaining venetoclax effects in treating CLL. Opaganib has shown potential as add-on therapy in several preclinical oncology models and is currently undergoing a Phase 2 clinical trial in combination with darolutamide in advanced prostate cancer. This new data now adds CLL to the list of potential cancer indications where opaganib has shown potential to bring additive therapeutic value.”
