Abbott Laboratories will be keeping everything crossed today as a US Food and Drug Administration advisory panel casts its eye over the company’s new prostate cancer therapy Xinlay (atrasentan). However, it’s not looking overly hopeful, as in briefing papers posted on the agency’s website, the panel said it would be scrutinizing the compound for both lack of efficacy and for the potential for serious cardiovascular events.

Abbott will present revised meta-analysis of two failed trials of Xinlay to the panel members [[15/12/04d]] but they appear to remain unconvinced, saying: “Xinlay does not demonstrate any clear evidence of clinical efficacy in men with hormone refractory prostate cancer in the only major trial of design adequate for a registration study.” In addition, “there are some serious cardiovascular safety issues observed in both major randomised trials” that were submitted as part of the regulatory dossier, the FDA states.

When it filed for approval of Xinlay, Abbott had originally hoped to garner approval for use in patients with hormone refractory prostate cancer [[15/12/04d]]. However, following the failed Phase III trial, it limited the proposed labelling to men with confirmed bone metastases.

The original pivotal trial failed to achieve significance not only in terms of the primary endpoint of time to disease progression, but also on four out of five secondary endpoints – including overall survival and progression-free survival. In contrast, the briefing papers show Abbott’s new meta-analysis pointing to a significant 20% reduction in time to disease progression and 80% reduction in time to bone pain for Xinlay receivers. But it is not looking good for Abbott, as the agency has dismissed this statistical review as “hypothesis-generating,” adding: “The analysis for patients with bone metastases at baseline was not pre-specified. Hence, the observed difference in this subgroup is considered as an exploratory and hypothesis generating analysis.”

It looks as if the most possible outcome for Abbott is a call for additional studies to be conducted, but the US biotechnology company could also be left with a bad taste in its mouth after the drug regulator pointed to an “excessive” number of protocol violations in both studies. Also, in terms of safety, the agency has expressed particular concern about the death rates observed in the Phase III study: eight Xinlay patients versus two placebo receivers suffered fatal cardiovascular events. “Xinlay is known to cause [congestive heart failure] from previously performed Phase II trials,” the agency notes. Furthermore, the Phase III study also found an increase in number of arrhythmias and cardiovascular events such as myocardial infarction, angina pectoris and stent placement in the Xinlay arm.