FDA reviewers highlight mixed safety for Spiriva Respimat

An FDA reviewer said mortality data for Spiriva Respimat tiotropium from Boehringer Ingelheim GmbH (Ingelheim, Germany) are "not entirely consistent," between the Phase III TIOSPIR trial and a pooled analysis of placebo-controlled trials for the chronic obstructive pulmonary disease (COPD) product. However, the reviewer noted that TIOSPIR was designed specifically to address an "observed mortality imbalance" and therefore data from that trial may outweigh a mortality imbalance driven by fatal myocardial infarctions in the pooled analysis. The comments came in Spiriva HandiHaler. FDA issued a complete response letter for Spiriva Respimat in 2008 in part due to a "numerical increase in deaths" in two 48-week Phase III trials of the product. Boehringer subsequently designed and ran outcomes trial TIOSPIR to compare all-cause mortality of Spiriva Respimat and Spiriva HandiHaler. Last year, Boehringer said Spiriva Respimat met the trial's co-primary endpoint of non-inferiority to Spiriva HandiHaler in the risk of death in about 17,000 COPD patients (see BioCentury Extra, Aug. 30, 2013). ...