An IDMC told Bayer that it should unblind its Phase III clinical trial in prostate cancer in order to further analyze an increased number of fractures and deaths.
An Independent Data Monitoring Committee (IDMC) told Bayer that it should unblind its Phase III clinical trial in prostate cancer in order to further analyze an increased number of fractures and deaths.
The company is conducting a Phase III clinical trial of radium Ra 223 dichloride (radium-223) in combination with abiraterone acetate and prednisone/prednisolone in prostate cancer. The treatment arm was focused on patients with asymptomatic or mildly symptomatic, chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). The study compared this population to patients receiving placebo. The primary endpoint is symptomatic skeletal event-free survival (SSE-FS).
The trial filled its enrollment in September 2016, with 806 patients. As a result, no patients in the combination arm of the trial are currently receiving radium Ra 223 dichloride because as part of the trial design, they only received it for up to 6 doses, one dose every four weeks.
In 2016, trials showed that the combination of Bayer’s radium-223 (Xofigo) with Zytiga (abiraterone) significantly cut bone pain in men with prostate cancer.
John Carroll with Endpoints News, writes, “The company, which has been pursuing new cancer drugs as a core approach to pipeline construction, had enrolled 806 patients who either got the combo or just Zytiga, a well-established blockbuster that helped change the standard of care in prostate cancer. Now they’ll begin the work to see why adding Xofigo—which uses targeted alpha radiation to kill cancer cells—would also trigger more deaths and fractures. This combination has been a key part of Bayer’s strategy to expand its market for Xofigo, which hit the market with bullish peak sales estimates of $1.5 billion.”
Combination drugs are a trend in oncology drug development, following in the largely successful path of HIV/AIDS treatments. They are often successful in cancer, although there appears to be a high risk of safety issues.
This was underscored in September when the U.S. Food and Drug Administration (FDA) placed a partial clinical hold on five clinical trials and a full clinical hold on one in the Celgene FUSION program. That trial tested AstraZeneca’s Imfinzi with several of Celgene’s oncology compounds. Similar problems have happened to Merck with combination trials with Keytruda and Bristol-Myers Squibb.
“Patient safety is our top priority,” said Mike Devoy, member of the Pharmaceuticals’ Division Executive Committee and chief medical officer at Bayer, in a statement. “We are therefore unblinding the study to thoroughly analyze the data. 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 indications remains favorable. We remain committed to further exploring the potential of radium-223 across multiple tumor types with significant unmet medical need, including prostate cancer.”
The company indicated that more than 18,000 patients in the U.S. have been treated with radium-223 since it was approved in 2013. “The benefit-risk profile demonstrated in the Phase III ALSYMPCA trial which resulted in the approval of Xofigo remains favorable.”
Prostate cancer, if it spreads beyond the prostate, often grows into nearby tissues or lymph nodes before metastasizing to the bones. CRPC is an advanced type of prostate cancer in which about 90 percent of patients develop bone metastases.
