The FDA has hit the green light for Xofigo--initially called Alpharadin or radium-223 chloride--for castration-resistant prostate cancer, demonstrating the agency's growing comfort with targeted cancer therapies that arrive at the agency with compelling overall survival benefits for patients. The approval comes just three months after the FDA granted priority review status for Alpharadin, a radiopharmaceutical from Bayer and Norway's Algeta that will now enter an increasingly competitive--and growing--market.
The treatment relies on the pinpoint delivery of alpha radiation to combat cancer. In a late-stage study with 922 patients--which was ended early after the monitoring committee determined the drug had achieved the primary endpoint--the treatment extended overall survival by 44 percent, with patients living a median average of 14 months compared to 11.2 months in the placebo arm. The treatment also delayed painful bone metastases, reducing bone pain and offering a better safety profile, with a median 64% delay in the first "skeletal event" for patients. The improved safety data reflected what researchers had also seen in Phase II.
"Xofigo binds with minerals in the bone to deliver radiation directly to bone tumors, limiting the damage to the surrounding normal tissues," said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "Xofigo is the second prostate cancer drug approved by the FDA in the past year that demonstrates an ability to extend the survival of men with metastatic prostate cancer."
The big idea, originating with Algeta's scientific founders, was that alpha particles can demolish cancer cells far more effectively than standard radiation therapies. Because they have a very narrow target range, down to a few millionths of a meter, it's possible to pinpoint tumors without devastating healthy tissue--significantly easing side effects.
Bayer signed on as the deep-pocket partner back in 2009 in an $800 million deal, one of several strategic steps that have now delivered a growing oncology business for Bayer. The pharma company--with a $4 billion R&D budget--markets Nexavar with Onyx Pharmaceuticals ($ONXX), recently obtained an approval for Stivarga and now has a new cancer product with blockbuster potential. But Algeta also hung on to co-promotion rights in the U.S., marking a major turning point in the company's development.
Not all analysts expect the treatment to achieve full blockbuster status, though a few project peak sales to break the billion-dollar mark. Alpharadin, which is approved for use after surgery and testosterone-lowering therapy, will now elbow its way into a fast-changing market for prostate cancer. Johnson & Johnson's ($JNJ) oral drug Zytiga has blitzed the market, gaining speed in the pre-chemo population after gaining approval for late-stage patients. Medivation's ($MDVN) Xtandi, partnered with Astellas, is growing fast as well. Both therapies have been stealing market share away from Dendreon's ($DNDN) troubled Provenge, a pioneering treatment that is both complex and expensive. Sales of Provenge declined significantly in the first quarter, while analysts expect to see the market for prostate cancer drugs grow significantly.
The approval will also continue to bedevil Exelixis ($EXEL), which has been pushing the clinical development of cabozantinib for prostate cancer. Already approved for thyroid cancer, Exelixis's management has persisted in pursuing a late-stage trial called COMET-2 for prostate cancer that focuses on bone pain reduction rather than overall survival as the primary endpoint. As the FDA made clear recently with Aveo's ($AVEO) tivozanib, an OS goal post remains the agency's gold standard for new cancer therapies. Exelixis has made overall survival the main goal of its COMET-1 study of prostate cancer patients, with data from both COMET studies expected in the first half of 2014.
Algeta is also convinced there's a second act for their alpha-radiation approach. The company has been zeroing in on combining thorium-227 with cancer-targeting antibodies for a next-gen pipeline. And now the biotech will have product revenue to back their R&D efforts.
- here's the press release
Editor's note: This story has been updated to include details about Exelixis's COMET-1 and COMET-2 studies.