Lilly has been hit by the news that its ramucirumab drug candidate failed a phase III trial in breast cancer, although positive data from a stomach cancer study softened the blow.
Ramucirumab will no longer be developed as a treatment for breast cancer in the wake of the TRIO-012 study, which compared first-line treatment with the drug to placebo – on top of background therapy with docetaxel – in patients with unresectable HER2-negative tumours.
The results of the RAINBOW trial of ramucirumab in combination with paclitaxel in patients with advanced gastric cancer were positive, however, and reinforce the findings of an earlier study of the drug as a monotherapy that formed the basis of a ‘rolling’ marketing application for the drug in the US.
The drug works by blocking vascular endothelial growth factor (VEGF) and is an angiogenesis inhibitor, designed to prevent blood vessels being formed in tumours thereby depriving the growing cancer cells of nutrients and oxygen.
Lilly has had mixed fortunes in its cancer pipeline of late, with positive results for necitumumab in squamous non-small cell lung cancer (NSCLC), although it was forced to drop lymphoma candidate enzastaurin after disappointing phase III results and also halted development of necitumumab for non-squamous NSCLC.
The cancer portfolio has become increasingly important for Lilly following other late-stage development failures such as schizophrenia candidate pomaglumetad methionil and tabalumab for rheumatoid arthritis, and upcoming patent expiries for big-selling brands such as the antidepressant Cymbalta (duloxetine).
“Cancer is complex and patients with different tumour types may have varied responses due to distinct tumour biologies and individual patient characteristics,” said John Mackey of the University of Alberta in Canada, who served as principal investigator for the TRIO-012 trial.
“Unfortunately, anti-angiogenic agents have not yet been able to demonstrate an overall survival benefit for patients with metastatic breast cancer,” he added.
Ramucirumab was originally developed by ImClone Systems, which was bought by Lilly in 2008 in a $6.5bn deal that focused on ImClone’s colorectal and head and neck cancer therapy Erbitux (cetuximab) as well as a pipeline of other oncology candidates including necitumumab.