Trastuzumab-DM1 regulatory update

FDA refused to file a BLA from Genentech Inc. for trastuzumab-DM1 (T-DM1) for third-line advanced HER2-positive breast cancer. The application, which was submitted last month, had requested accelerated approval. According to Genentech, FDA said T-DM1 trials did not meet the standard for accelerated approval because all available treatments approved for metastatic breast cancer, regardless of HER2 status, had not been exhausted in the study population, including Gemzar gemcitabine, Ixempra ixabepilone and hormonal therapies.

The application was based on data from a single-arm Phase II trial in patients with advanced HER2-positive breast cancer who had received an average of seven prior therapies, including two HER2 targeted agents. Genentech, which is a unit of Roche, said it expects to resubmit a BLA in mid-2012 seeking accelerated approval for second-line treatment based on progression-free survival (PFS) data from the ongoing Phase III EMILIA trial. The trial compares T-DM1 to Tykerb lapatinib plus Roche's Xeloda capecitabine in patients with advanced HER2-positive breast cancer who failed first-line treatment. Genentech said it plans to amend the EMILIA trial to include overall survival as an endpoint in addition to the primary endpoint of PFS. The company hopes to use overall survival data from EMILIA to convert accelerated approval of the compound into full approval. ...