Bayer Suspends Production of Radium-223 Due to Manufacturing Problem

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Oliver Sartor, MD

Production of the prostate cancer drug radium-223 (Xofigo) has been suspended indefinitely by its maker, Bayer HealthCare Pharmaceuticals, due to a manufacturing problem. The company confirmed the manufacturing suspension in a statement released toTargeted Oncology.

According to the FDA’s website and one of its spokesmen, the drug has been in shortage since October 7. The agency is working with Bayer on the issue.

“Bayer HealthCare is currently experiencing a drug shortage of Xofigo (radium Ra 223 dichloride) Injection,” the company wrote in its statement. “Through the standard inspection process, Bayer determined that recently produced drug product did not meet the high quality standards, due to small fibrous particles found in some of the vials. Therefore, this drug product was not distributed. An expert team is working diligently to solve this matter. At this time, Bayer is unable to anticipate when distribution of Xofigo can be resumed.”

The company noted that, “All previously released product met the quality standards in place for Xofigo.”

However, because the drug expires quickly once it has been manufactured—it has a half-life of 11 days—the halt in production at the world’s only radium-223 manufacturing site, in Norway, means there is no longer any supply of the medication available to patients, Oliver Sartor, MD, said in an interview withTargeted Oncology.

“They are selling ripe tomatoes,” Sartor said. “And the supply ran out—all the ripe tomatoes have gone bad.”

Sartor, the Laborde Professor for Cancer Research and medical director at Tulane Cancer Center in New Orleans, Louisiana, was the principal North American investigator for the ALSYMPCA trial that led to the FDA’s May 15, 2013, approval of radium-223, an alpha-emitting radiopharmaceutical that targets osteoblastic bone metastases in men with castration-resistant prostate cancer. The FDA's decision was based on a 3.6-month improvement in median overall survival for radium-223 compared with placebo.

“Doctors can seek alternative therapies, so this is most problematic not so much for patients who have yet to start, but for those who have already started taking radium-223,” Sartor said. “The FDA approved the course of therapy as 6 doses at monthly intervals. Relatively small delays in therapy, such as 1 to 3 weeks, are probably not consequential, but we don’t know the duration of this delay.”

Sartor added that he would not recommend that doctors restart the entire course of radium-223 in these patients once supply has resumed, since “nobody has data on that.”

The halt in production will also affect patients enrolled in clinical trials of radium-223—including several being conducted at Tulane.

Neal D. Shore, MD, of Atlantic Urology Clinics in South Carolina, whose site was the first in the world to administer the drug to a patient outside clinical trials, said that delays of even 4 weeks may not jeopardize the benefit patients experience from radium-223.

“In the ALSYMPCA trial, there was allowance for patients to be included within the trial with upwards of 8 weeks between cycles, because life events, other comorbidities, access problems, and all sorts of things can happen,” he said. “What’s been pretty clear in looking through that data is that, even with 8 weeks between cycles, patients still did therapeutically very well.”

While Shore is an investigator in a trial of radium-223 combined with abiraterone (Zytiga), he said he is not worried the study will be affected by the shortage, about which he hopes to hear “something positive” as soon as next week.

Sartor called the production delay “a big issue” for Bayer, which “made a huge investment, bought Algeta, [with which it had developed radium-223,] and is treating thousands of patients across the globe” with the drug. “The company is making this an absolute top priority.”

In its statement, Bayer said it is communicating with physicians and clinical trial investigators about the status of the production suspension, and is working with the FDA. Sartor said he has received such communications from Bayer, both in his capacity as a co-author of the ALSYMPCA trial and as a physician who regularly prescribes the drug to patients.

“Bayer is committed to ensuring patient access to Xofigo, and we are working to restore supply as quickly as possible,” the company wrote. “For further information, patients should contact their healthcare provider or the Bayer Call Center at 1-888-84-Bayer, or 1-888-842-2937.”