Amgen, posted results from preclinical studies suggesting a significantly greater reduction in tumour growth when AMG 386, a recombinant Fc-peptide fusion protein (peptibody) designed to bind angiopoietins 1 and 2, thereby inhibiting Tie2 dependent stimulation of endothelial cells, was combined with either of two vascular endothelial growth factor (VEGF) inhibitors -- bevacizumab or motesanib diphosphate (AMG 706) -- compared with either treatment alone (p less than 0.05).

Angiopoietins, together with VEGFs, are key cytokines that regulate neovascularisation. The results of preclinical studies that investigated the growth of human colon tumour cells in this combination were presented at the 2008 American Association for Cancer Research (AACR) annual meeting in San Diego.

"Tumours depend on a reliable blood supply to grow and survive. By targeting angiogenesis - the process underlying the formation and growth of new blood vessels - we hope to achieve clinically meaningful control of many cancers," said, Roger M. Perlmutter, executive vice president, research and development, Amgen. "What's encouraging about these early results is that they indicate that blocking more than one angiogenesis pathway may offer enhanced potential to inhibit tumour growth. We look forward to investigating this finding further."

The data were generated from three blinded studies of preclinical models of colon carcinoma randomised into three experimental groups. The models were treated with suboptimal doses of motesanib diphosphate (37.5 - 75 mg/kg QD, PO), bevacizumab (2.8 ug twice per week), AMG 386 (2.8 - 14 ug twice per week) or combinations thereof. In all three studies, greater reduction in tumour growth was observed when AMG 386 was combined with either motesanib diphosphate or with bevacizumab, compared to the tumour growth reduction seen with either VEGF inhibitor alone.

Angiogenesis, the process of new blood vessel formation, plays a critical role in many diseases, including cancer. New blood vessels constantly form during an embryo's development, but in adults angiogenesis normally only takes place as part of specific processes such as recovering from an injury, when the growth of new blood vessels promotes wound healing. In cancer, tumours grow and metastasize in part by secreting angiogenic substances, such as VEGF, that can induce capillary growth into the tumour.

Anti-angiogenesis research is an important area of research for Amgen. In 2007, Amgen initiated four phase II studies of AMG 386 for the treatment of renal cell, metastatic breast, ovarian and gastric cancers.

Motesanib diphosphate is a highly selective, investigational oral agent that is being evaluated for its ability to inhibit angiogenesis and lymphangiogenesis by targeting VEGF 1, 2 and 3. It is also under investigation for its potential direct anti-tumour activity by targeting platelet-derived growth factor receptor ("PDGFR") and stem cell factor receptor ("c-kit") signalling.

A phase III study examining the potential utility of motesanib diphosphate in the treatment of non-small-cell lung cancer (NSCLC) is currently ongoing, as are phase II studies in patients with metastatic breast cancer or NSCLC comparing the activity of motesanib diphosphate with that observed using bevacizumab. In February 2008, Amgen announced the establishment of a partnership with Takeda supporting the worldwide development and commercialisation of motesanib diphosphate, and the development and commercialisation of up to 13 phase II molecules, including AMG 386, in Japan.