Executive Summary

Curis' first-in-class Hedgehog pathway inhibitor GDC-0449 failed in a Phase II clinical trial in metastatic colorectal cancer, where it was studied in combination with partner Roche/Genentech's Avastin and FOLFOX or FOLFIRI chemotherapy, the firms announced June 16. The trial did not meet the primary endpoint of extending time from randomization to disease progression or death in patients getting the GDC-0449 combination versus the standard of care arm. Curis is confident that other trials will bear out the Hedgehog inhibitor's potential, because the pathway is thought to act by different mechanisms in other tumor types; the firm noted that proof of concept has been achieved in advanced basal cell carcinoma, which is "almost always" the result of a specific mutation in a component of the Hedgehog pathway. Roche already has a pivotal Phase II of GDC-0449 underway in advanced basal cell carcinoma and the firm has indicated it expects to initiate a Phase II in operable basal cell carcinoma during the second half of 2010. Results are also expected in the second half from a randomized Phase II in advanced ovarian cancer in a maintenance setting, "which is evaluating the ability of GDC-0449 to slow the time to recurrence in patients ... in complete remission, by impeding the residual cancer cell's ability to grow," Curis said