Pfizer, AstraZeneca and Actelion last night each reported the failure of one of their drugs in pivotal clinical trials. Pfizer and AstraZeneca separately announced that Phase III trials evaluating their respective drugs, Sutent® and zibotentan, failed to demonstrate the treatments improved overall survival in patients with advanced castration-resistant prostate cancer (CRPC). Actelion said data from the Phase III Conscious-2 study with its Pivlaz® (clazosentan) candidate failed to reach statistical significance in terms of reducing vasospasm-related morbidity and all-cause mortality in clipped patients following aneurismal subarachnoid hemorrhage (aSAH).
Pfizer’s Phase III Sun 1120 Sutent study has been stopped on the advice of the trial’s data monitoring committee, following an interim analysis that showed adding the drug to prednisone therapy was unlikely to impact on overall survival in patients whose CRPC disease had progressed following a docetaxel-based chemotherapy regimen. Sutent is an oral multikinase inhibitor that is already approved for the treatment of both advanced renal cell carcinoma and gastrointestinal stromal tumors in patients who are intolerant to imatinib or whose disease has progressed after imatinib therapy. Sutent is separately being evaluated in a Phase III trial as an adjuvant therapy for renal cell carcinoma.
AstraZeneca, meanwhile, confirmed it has no immediate plans to file regulatory submissions for its anticancer candidate zibotentan after the Phase III Study 14 trial failed to show any survival benefits of adding the endothelin pathway blocker to standard of care in patients with metastatic CRPC. The firm is continuing with the Phase III Enthuse CRPC development program for zibtentan, however. Study 15 will evaluate zibotentan in comparison with placebo in men whose disease has not yet metastasized. Study 33 will evaluate chemotherapy alone, with chemotherapy plus zibotentan in patients who have been prescribed chemotherapy due to metastases.
Actelion CEO, Jean-Paul Clozel, M.D., admitted the firm was disappointed that the Phase III Conscious-2 study found that Pivlaz therapy only resulted in a nonsignificant (17%) benefit in terms of its primary endpoint in aSAH patients. The firm is now considering how or whether to continue with its Phase III development program for the endothelin receptor antagonist. Another Phase III trial, Conscious-3, is ongoing in aSAH patients that have undergone coiling to secure their aneurysm. Actelion says an update on plans for Pivlaz will be made when the firm releases its third quarter results in October. The previously completed dose-ranging Conscious-1 study did show treatment with Pivlaz significantly reduced moderate or severe vasospasm at all tested doses, with a relative risk reduction of 65% compared with placebo.