[schoonder]

The FDA was fully justified in their ruling to issue a Refuse to File (RTF) letter re T-DM1. When questioned they surely will be able to identify directive(s) that support that decision. But therein lies the problem, what happens if particular directive(s) have flaws, are outdated, lack specificity, fail to take into account technological advances, or even more important, don't reflect the spirit of FDA's mandate?
Here we have an instance where FDA ruled that trial was incomplete because candidates that partook in this evaluation were not subjected to all possible metastatic breast cancer (MBC) remedies approved for this disease. Let's not deny that outcome of this scrutiny by FDA of patient population is factual; indeed not all available MBC treatment options were accounted for. However,let's look at the other side of the coin, are there mitigating reasons why Genentech decided not to include this missing collection of infrequently prescribed, low in its effectiveness, yet highly toxic medication as part of their trial? The answer of course is a resounding YES:
This trial was all about finding new options for “HER2- positive” women whose breast cancer progressed while on Herceptin or Tykerb, in third-line or greater setting, for which today there are no standard treatments or guidelines. FDA was fully aware of trial’s intent to address an unmet medical need strictly for “HER2-positive” patients, a small subset of overall MBC population. This study included patients that had failed on average seven (range of 3-13) regimens including both Herceptin and Tykerb which are known to work best in HER2-positive breast cancer. Not all regimens were accounted for, but the most predominant, most meaningful, most effective and all these therapies were no longer therapeutic.
One can only surmise that Genentech ruled in favor of the most immediate and timely considerations to bring what they observed to be an astonishingly effective, targeted drug to Her2-positive patients who were so desperately in need of new, viable treatment options. This urgency to save lives, led them to stop their time consuming, probably inconsequential and wasteful search to find further candidates that had been medicated with these for Her2-positive MBC rarely prescribed, ineffective therapies. As the Biologics License Application (BLA) Priority Review filing based on just phase II results strongly suggests, time considerations to market what promises to be a very effective drug was a strong driving force behind Genentech's motivation.
FDA’s uncompromising position to refuse to accept this filing based on a minor technicality, most likely brought on by shortcomings in their directive(s) dealing with newly “targeted” drugs like T-DM1, that are designed specifically for a small, Her2-positive overexpressing MBC patient population, is not only incomprehensible, but it is totally unacceptable. The consequence of this ruling, which appears to delay T-DM1’s approval process by at least two years, were instantaneous, the hope for a possible effective treatment option went poof, it disappeared into thin air and ultimately, it will result in premature demise for many an ill Her2-positive MBC patient.
Yes, this was such harsh and inappropriate ruling by FDA.