RedHill and Bayer Launch Phase 2 Trial Combining Opaganib with Darolutamide for Advanced Prostate Cancer
Key Insights
RedHill Biopharma initiates an 80-patient Phase 2 study testing opaganib in combination with Bayer's darolutamide for metastatic castrate-resistant prostate cancer (search), with financial backing from Bayer and Ramsay Hospital Research Foundation (search).
The study will utilize a novel PCPro biomarker test to identify patients with poor prognosis who may benefit from the combination therapy, with the primary endpoint being 12-month radiographic progression-free survival.
Prostate cancer (search) affects approximately 1.5 million new patients annually worldwide, with the study targeting a significant unmet need in the $12 billion market for patients who develop resistance to standard treatments.
A groundbreaking clinical trial is set to evaluate a novel combination therapy for men with advanced prostate cancer (search), as RedHill Biopharma launches a Phase 2 study investigating opaganib with darolutamide in metastatic castrate-resistant prostate cancer (search) (mCRPC).
The placebo-controlled randomized study, involving 80 patients, will assess whether adding opaganib to darolutamide treatment can enhance outcomes for patients who typically show poor response to standard therapies. Bayer and the Ramsay Hospital Research Foundation (search) are providing financial support for this innovative research initiative.
Professor Lisa Horvath, Chief Clinical Officer and Director of Research at Chris O'Brien Lifehouse, will lead the study in collaboration with the Australian and New Zealand Urogenital and Prostate Cancer (search) Trials Group (ANZUP (search)). The research employs a strategic approach by utilizing the PCPro companion lipid biomarker test to identify patients most likely to benefit from the combination treatment.
Scientific Rationale and Mechanism of Action
The study builds on compelling preclinical evidence showing opaganib's ability to enhance androgen receptor signaling inhibitor efficacy. This effect occurs through the simultaneous inhibition of three sphingolipid-metabolizing enzymes (SPHK2, DES1, and GCS) in human cells, potentially offering a solution to darolutamide resistance in mCRPC patients.
"Cancer cells may block apoptosis, an important cell-level process designed to help the body get rid of unneeded or abnormal cells - critical in fighting the spread of cancer," explains Professor Horvath. "Our prior research indicates that opaganib could provide the key to overcoming darolutamide resistance in men with mCRPC."
Study Design and Patient Selection
The trial will screen approximately 200 patients to identify those who are PCPro-positive, estimated to be about 40% of the screened population. Eligible participants will be randomized in a 1:1 ratio to receive either:
- Darolutamide 600mg twice daily + placebo (40 patients)
- Darolutamide 600mg twice daily + opaganib 500mg twice daily (40 patients)
The primary endpoint focuses on improved 12-month radiographic progression-free survival (rPFS), with several secondary and exploratory endpoints also under evaluation.
Market Impact and Unmet Need
Dr. Mark Levitt, RedHill's Chief Scientific Officer, emphasizes the significant market opportunity: "The prostate cancer (search) market, valued at approximately $12 billion, represents a substantial opportunity for innovative treatments. Darolutamide has established itself as a key therapy, and if opaganib can successfully reduce resistance to darolutamide therapy, this could mark a significant breakthrough in managing advanced treatment-resistant mCRPC."
Disease Burden and Current Treatment Landscape
Prostate cancer (search) remains the second most diagnosed cancer globally, with approximately 1.5 million new cases annually and nearly 400,000 deaths. The disease burden has increased dramatically, with cases rising by almost 120% between 1990 and 2019.
While early-stage prostate cancer (search) shows excellent survival rates, patients with advanced disease face significantly poorer outcomes. The five-year survival rate drops from 100% for Stage 1 to just 28% for Stage 4 disease, highlighting the urgent need for more effective treatment options for advanced cases.
Current standard of care typically involves androgen deprivation therapy (ADT) using AR signaling inhibitors. However, all metastatic patients eventually develop resistance to these treatments, often due to elevated levels of ceramide and sphingosine-1-phosphate, which promote cancer growth and drug resistance.