Biologics clinical trials, research, and FDA actions.

Hopes raised, hopes dashed — the last half of 2012 has seen plenty of both. Enthusiasm over a bumper crop of U.S. Food and Drug Administration approvals has been tempered by a long list of phase 3 trial disappointments. Oncology agents led the way, starting with two drugs being studied for the treatment of non-small cell lung cancer. The addition of Eli Lilly’s pemetrexed (Alimta) to a regimen of bevacizumab (Avastin) and chemotherapy produced improvements in progression-free survival (PFS) but not overall survival (OS). ArQule and Daiichi Sankyo stopped a phase 3 study of tivantinib after concluding that improvements in OS would not be reached. For ArQule, the silver lining was the FDA’s grant of a special protocol assessment, allowing the start up of a phase 3 trial of tivantinib in patients with liver cancer. Amgen ended a large phase 3 trial of ganitumab after a data monitoring committee determined that the addition of ganitumab to gemcitabine (Gemzar) would not result in significant OS improvements in patients with pancreatic cancer versus gemcitabine alone. A phase 2 trial of ganitumab in locally advanced pancreatic cancer was also stopped. Two separate studies of agents to treat kidney cancer also caused consternation. Temsirolimus (Torisel), currently on the market for advanced renal cell carcinoma, was no better at extending PFS when combined with bevacizumab than a combination of bevacizumab and interferon alfa2a. And Aveo is reevaluating data from a head-to-head trial of its tivozanib versus sorafenib (Nexavar) after the FDA expressed concern about OS data that Aveo planned to include in a new drug application later this year. Not all news from oncology was disappointing. Immunogen released a deeper dive into OS data for trastuzumab emtansine, or T-DM1 (Kadcyla), showing a 5.8-month OS benefit in previously treated HER2-positive metastatic breast cancer patients versus lapatinib (Tykerb) plus capecitabine (Xeloda). And Celgene’s multiple myeloma oral drug, pomalidomide — a derivative of thalidomide — improved PFS in patients who were refractory to lenalidomide (Revlimid) and bortezomib (Velcade).