Abbott Laboratories announced its intent to submit a New Drug Application (NDA) for Xinlay by the end of 2004 with the US FDA. Abbott is seeking approval of Xinlay for men with metastatic, hormone-refractory prostate cancer and has been granted fast-track designation from the FDA, a company release said.
Abbott intends to submit an NDA based on a meta-analysis that examined pooled data from two large, randomized, well-controlled clinical trials (M96-594 & M00-211) of Xinlay with a total patient population of 1,097. The intent to treat analysis showed a delay in time to disease progression (p=0.013) in men with metastatic, hormone- refractory prostate cancer who took the drug versus those who took placebo.
The meta-analysis was presented at the American Society of Clinical Oncology in June. Analyzed separately, the two studies showed trends in favour of Xinlay, but did not show statistical significance, the release says.
"We are very excited about the possibility to bring the first of several Abbott- discovered oncology drugs to patients," said John Leonard, vice president for global pharmaceutical development at Abbott Laboratories. "We are looking at novel approaches to treat prostate cancer with the hope of providing additional treatment options to patients sooner," he added further.
The two individual studies pooled for the meta-analysis tested the same patient population with similar baseline demographics, used the same primary endpoint of time to disease progression (radiographic progression was more explicitly defined in the M00-211 protocol) and were placebo-controlled, double blind, multinational studies.
In the larger M00-211 study, patients were randomized to 10mg of Xinlay or placebo. In the M96-594 study, patients were randomized to 10mg or 2.5mg of Xinlay, or placebo. Abbott has conducted statistical tests for heterogeneity of the studies and on the overall treatment effect to support the rigor of the meta-analysis.
Xinlay was generally well tolerated in both studies among all patients. The most common associated adverse events for Xinlay vs. placebo were, headache (20 percent vs. 13 percent), peripheral edema (38 percent vs. 13 percent) and rhinitis (32 percent vs. 14 percent), respectively.
Xinlay, an oral, once-daily, non-hormonal, non-chemotherapy, anti-cancer agent, belongs to a class of compounds known as selective endothelin-A receptor antagonists (SERAs). SERAs antagonize the effect of endothelin (ET-1), one of the proteins thought to be involved in the stimulation of the spread of cancer cells. Xinlay is the result of Abbott's discovery effort in oncology.
Xinlay has been studied in phase II and phase III clinical trials in patients with metastatic, hormone-refractory prostate cancer. It is currently in its second phase III pivotal trial involving men with hormone-refractory prostate cancer that has not spread (non-metastatic). It is also being evaluated in a phase II trial in hormone-naïve men with rising prostate-specific antigen (PSA) following prostate cancer surgery. Additionally, Abbott continues to explore Xinlay in other cancers, including kidney, ovarian, brain and non-small-cell lung cancers.