FDA REVIEWERS QUESTION EFFICACY OF ABBOTT'S XINLAY, OSI'S TARCEVA INDICATION
FDA drug reviewers have raised doubts about the clinical benefits of two proposed cancer treatments -- Abbott Laboratories' experimental prostate cancer drug Xinlay and OSI Pharmaceutical's proposed pancreatic cancer indication for Tarceva.
The FDA's Oncologic Drugs Advisory Committee will meet today to consider Xinlay (atrasentan HCl), which is proposed to treat men with metastatic hormone-refractory prostate cancer. The panel also will discuss a supplemental new drug application for Tarceva (erlotinib HCl), which has a proposed indication -- in combination with gemcitabine chemotherapy -- as the first-line treatment for advanced, unresectable or metastic pancreatic cancer.
The drugmakers could face a tough time convincing the panel to recommend approval if the FDA staff review of the product applications are any indication.
The two studies submitted on Xinlay "failed to demonstrate a delay in disease progression" for subjects in the atrasentan treatment group compared with those in the placebo group, FDA statistical reviewer Shenghui Tang writes in background materials posted recently to the FDA website. The observed data "do not support the sponsor's claim of efficacy of atrasentan," the document states.
The FDA's clinical review of Xinlay echoed this point and also raised safety questions. "There are some serious cardiovascular safety issues observed in both major randomized trials," states the clinical review by FDA scientist Aman Ibrahim.
As with Xinlay, the FDA review staff raised questions about the efficacy of Tarceva (erlotinib) -- in combination with gemcitabine chemotherapy -- in treating pancreatic cancer. Tarceva already is approved as a therapy for lung cancer.
According to OSI's briefing documents, Tarceva is the first and only agent that -- when added to standard gemcitabine therapy -- has demonstrated in a large, randomized, placebo-controlled Phase III trial a "statistically significant survival benefit" over gemcitabine alone in patients with pancreatic cancer.
"This clinical benefit was achieved with only a modest change in the safety profile compared with gemcitabine alone, with generally manageable adverse events requiring few dose modifications or discontinuations and without deterioration of quality of life," OSI said.
To view the background materials for the meeting, access http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4174B1-00-index-with-disclaimer.htm (http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4174B1-00-index-with-disclaimer.htm).