NEW YORK – RedHill Biopharma on Tuesday said it will begin a Phase II trial testing its sphingosine kinase-2 (SPHK2) inhibitor opaganib with Bayer and Orion's anti-androgen therapy Nubeqa (darolutamide) in patients with metastatic castration-resistant prostate cancer (mCRPC) and identify best responders using a lipid biomarker companion test.
In the trial, investigators will compare opaganib-Nubeqa to Nubeqa alone in about 80 patients with mCRPC who have a poor prognosis and may benefit from the therapy as determined by the lipid signature test, PCPro, which measures circulating ceramide, sphingomyelin, and phosphatidylcholine in plasma.
Plasma lipidomic profiles enriched with those lipids have been associated with decreased overall survival in men with mCRPC treated with docetaxel. The researchers aim to enroll patients who have not had androgen receptor signaling inhibitors such as Nubeqa, Astellas Pharma's Xtandi (enzalutamide), Janssen's Erleada (apalutamide), and Janssen's Zytiga (abiraterone). The study's primary endpoint is improvement in the 12-month radiographic progression-free survival rate.
The study is supported by Bayer and the Sydney, Australia-based Ramsay Hospital Research Foundation. It will be led by researchers from Sydney's Chris O'Brien Lifehouse and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group.
Opaganib is designed to overcome resistance to Nubeqa. The drug enhanced the efficacy of androgen receptor signaling inhibitors by simultaneously inhibiting three sphingolipid-metabolizing enzymes in in vitro studies. Redhill has also studied opaganib in partnership with US health agencies in several other indications including acute radiation syndrome, Ebola virus, and SARS-CoV-2.
"Men with mCRPC have few treatment options available to them, and those positive for the PCPro marker of [androgen receptor pathway inhibitor] resistance seem to have a particularly poor prognosis," Mark Levitt, CSO of RedHill, which is headquartered in Raleigh, North Carolina, and Tel-Aviv, Israel, said in a statement. "[Nubeqa] is establishing itself as a key therapy in the treatment of prostate cancer, a market worth approximately $12 billion in 2023, and, if the addition of opaganib can reduce the resistance to [Nubeqa] therapy, this could represent a significant breakthrough in improving the ability to manage treatment-resistant mCRPC for improved outcomes."