According to a media release issued by AstraZeneca earlier today, the company has stopped a second clinical trial of their endothelin receptor antagonist zibotentan because “zibotentan monotherapy was unlikely to meet its primary efficacy endpoints … and therefore unlikely to benefit patients with non-metastatic CRPC.”
This is the second of three randomized Phase III clinical trials of zibotentan in the ENTHUSE program that has been stopped early because of failure to meet study goals. A previous study of zibotentan monotherapy in men with metastatic, castration-resistant prostate cancer (mCRPC) was terminated early last September. The only Phase III trial of zobotentan that is now continuing is a randomized Phase III clinical trial (ENTHUSE Study 33) of zibotentan in combination with docetaxel and prednisone in men with mCRPC.
This means that zibotentan, like Abbott’s endothelin receptor antagonist, atrasentan (Xinlay), appears to have insufficient clinical activity to be effective on its own in the treatment of prostate cancer. Like zibotentan, atrasentan is also being tested in combination with docetaxel and prednisone in men with mCRPC. It seems likely that results of the late stage clinical trials of both of these endothelin receptor antagonists will be available some time later this year.