FDA releases Xinlay briefing documents

FDA's clinical review of prostate cancer compound Xinlay atrasentan from Abbott (ABT) says the compound "does not demonstrate any clear evidence of clinical efficacy in the only major trial" with a design adequate for a registration study. The documents were released in advance of Tuesday's meeting of FDA's Oncologic Drugs Advisory Committee. ABT is seeking approval of Xinlay, a small molecule selective endothelin A receptor antagonist, to treat metastatic hormone-refractory prostate cancer in men with confirmed metastases. The PDUFA date for Xinlay is in the fourth quarter.

ABT intended to use a Phase III and a Phase II trial as the basis for registration, but FDA's review said the Phase II design "was not acceptable for a registration study." In addition to citing "major weaknesses" in design, FDA also said the Phase II trial had "major weaknesses in conduct and results," including a missed primary endpoint of time to disease progression. The Phase III trial also missed its primary endpoint of time to disease progression. Significance was seen in a retrospectively defined subset of patients with bone metastases at baseline, but the agency said that analyses other than the intent to treat analysis "should be considered exploratory and hypothesis-generating." ...