- German drugmaker Bayer AG's efforts to expand use of its prostate cancer drug Xofigo hit a major safety setback Friday, after the company disclosed a Phase 3 study of the therapy would be unblinded early due to a higher number of patient deaths occurring in the treatment group than in the placebo arm.
- An independent data monitoring committee flagged the imbalance, recommending Bayer analyze the new findings from the study, which pairs Xofigo with J&J's Zytiga and prednisone to treat castration-resistant prostate cancer that has metastasized to bones.
- No patient in the Phase 3 trial is currently receiving Xofigo, as enrollment into the study completed in September 2016 and the drug is only administered for up to 6 doses over 24 weeks. Bayer said it had informed the relevant health regulators of the unblinding and plans to gather more detailed data on the new signal.
Xofigo (radium-223 dicholoride) is one of Bayer's top cancer drugs, acquired in the German drugmaker's $2.9 billion purchase of Algeta in 2013. At the time, Bayer trumpeted Xofigo's sales potential and forecasted €1 billion in peak annual sales for the targeted alpha radiation therapy.
The drug have so far failed to live up to that billing, earning €307 million ($341 million) in sales through the first nine months of 2017. While Bayer has yet to fully investigate the safety signal uncovered by the Data Monitoring Committee, the imbalance seen in its Phase 3 ERA223 study raises new concerns.
Bayer enrolled 806 patients into ERA223, divided equally between groups receiving Xofigo together with Zytiga (abiraterone acetate) and prednisone or placebo. Patients in the treatment group were administered up to six doses of Xofigo spaced four weeks apart.
As a targeted alpha therapy, Xofigo is designed to selectively attack bone metastases of castration-resistant prostate cancer (CRPC). In ERA223, Bayer enrolled patients with asymptomatic chemotherapy-naive bone predominant CRPC, aiming to improve symptomatic castration-resistant event-free survival.
But more patients in the treatment group died or experienced bone fractures than those on placebo, prompting the study unblinding.
"Patient safety is our top priority. We are therefore unblinding the study to thoroughly analyze the data," said Mike Devoy, Bayer's chief medical officer, in a Nov. 30 statement. "It is important to note that, based on available data from previous trials as well as real-world use, the benefit-risk profile of Xofigo in its approved indication remains favorable."
Like other pharmas, Bayer is devoting more resources to oncology, recently inking a deal with the hot cancer biotech Loxo Oncology Inc. that could be worth as much as $1.5 billion. The German company also recently won U.S. approval for its PI3K inhibitor Aliqopa (copanlisib).
Behind the scenes, however, there appears to be some upheaval in Bayers's R&D operations. The disclosure about Xofigo comes a day after an announcement that the company would combine its research and development activities, including oncology, together under one organizational umbrella.
In the process, Andreas Busch, the company's now-former head of drug discovery, decided to leave the company and take a job as head of R&D at Shire plc.