Amgen and Takeda's trebananib peptibody missed its overall survival end point in a pivotal ovarian cancer trial, despite promising signals of progression-free survival.

The lowdown: Anti-angiogenesis drugs like Genentech/Roche's blockbuster bevacizumab — an antibody that inhibits vascular endothelial growth factor (VEGF) — offer efficacy in a range of oncology indications, but are limited by side effects including hypertension, thrombosis, emboli, bleeding, bowel perforation and central nervous system disorders. To side-step these adverse events, a few drug developers have targeted other drivers of angiogenesis, such as angiopoietin 1 (ANG1) and ANG2, which mediate vascular remodelling via the angiopoietin receptor TIE2. Amgen and Takeda had been leading the charge with their ANG1- and ANG2-binding peptibody trebananib — which is made by fusing peptides to a crystallizable fragment Fc domain — but they have recently hit a snag.

In trebananib's first Phase III trial, the median overall survival was 19.3 months with the treatment, versus 18.3 months in the control arm, the drug developers reported in November. The firms had previously reported that the median progression-free survival was 7.2 months in the trebananib arm versus 5.4 months in the control arm. “We continue to explore the potential of trebananib's novel anti-tumor mechanism of action in other cancer settings,” said Amgen's head of Research and Development, Sean Harper, in a statement.

Two other Phase III trials in ovarian cancer are ongoing. The firms are also testing the drug in Phase II trials in renal cell carcinoma, breast cancer and hepatocellular cancer.

At least three other ANG inhibitors are in clinical development. Roche's RG7221 is a bispecific antibody that binds both ANG2 and VEGFA. Roche initiated a Phase II trial of the bispecific therapy in patients with colorectal cancer in June. MedImmune's ANG2-specific antibody MEDI3617 is in Phase I development. And Amgen's ANG1- and ANG2-targeting monoclonal antibody AMG 780 is in Phase I trials. Pfizer had previously made it as far as Phase II with its ANG2-specific CVX-060, but discontinued development of the antibody in 2013.