Amgen 2007 Annual Report Download - page 32

AMG 655
AMG 655 is a fully human monoclonal antibody agonist directed against Death Receptor 5 (“DR5”). AMG
655 is designed to activate caspases and induces apoptosis in sensitive tumor cells. Phase 1b/2 studies in pancre-
atic cancer, NSCLC, CRC and soft tissue sarcoma are ongoing.
rhApo2L/TRAIL
rhApo2L/TRAIL is a soluble recombinant human protein that targets the pro-apoptotic death receptors DR4
and DR5, which are involved in the regulation of apoptosis (programmed cell death). rhApo2L/TRAIL is being
evaluated as a potential cancer therapeutic. A phase 1b study of CRC initiated in 2006 is ongoing. Phase 2 studies
were initiated in 2007 for the treatment of NSCLC in combination with chemotherapy both with and without
bevacizumab and NHL as a monotherapy and in combination with rituximab. We are developing this product in
collaboration with Genentech.
Motesanib diphosphate
Motesanib diphosphate is a highly selective, oral agent that is being evaluated for its ability to inhibit angio-
genesis and lymphangiogenesis by targeting vascular endothelial growth factor receptors 1, 2 and 3 (“VEGFR1-
3”). It is also under investigation for its potential direct anti-tumor activity by targeting platelet-derived growth
factor receptor (“PDGFR”) and stem cell factor receptor (“c-kit”) signaling, which may also confer direct anti-
tumor activity. In February 2008, we announced that Takeda will become our worldwide partner for motesanib
diphosphate in addition to an exclusive collaboration on up to 13 other programs in the Japanese market (see
“Joint Ventures and Business Relationships — Takeda Pharmaceutical Company Limited”).
In 2007, enrollment began for a phase 3 study in NSCLC. Additionally, we are conducting head-to-head
phase 2 studies of this agent versus bevacizumab in the treatment of metastatic breast cancer and NSCLC. Mote-
sanib diphosphate is also being investigated in combination with other anti-cancer therapies. Phase 1b
combination studies in multiple tumor types are ongoing.
In 2007, we completed a phase 2 trial in advanced thyroid cancer and were encouraged by the clear evidence
of biological activity in this setting, as judged by response rate criteria. However, based on our discussions with
the FDA, we have decided not to file for approval for motesanib diphosphate in thyroid cancer until there is more
clarity on what a regulatory filing package would constitute for this indication.
Romiplostim (formerly known as AMG 531)
Romiplostim (Nplate™) is a protein called a peptibody. The active peptide component stimulates the throm-
bopoietin (“TPO”) receptor resulting in increased platelet production. It is being investigated for the treatment of
chronic ITP. ITP is an autoimmune bleeding disorder characterized by an abnormal decrease in platelets, a con-
dition known as thrombocytopenia.
Data from two phase 3 clinical studies evaluating romiplostim for the treatment of thrombocytopenia in ITP
(studying pre- and post-splenectomy ITP) met both primary and secondary endpoints. Based on positive results
from these studies, we submitted a BLA with the FDA for the treatment of thrombocytopenia in adult patients
with chronic ITP in October 2007 and also completed regulatory filings for this indication in Europe, Canada and
Australia. The FDA has granted priority review for Nplate™ which will be discussed at the March 2008 ODAC
meeting. We expect a regulatory decision in the first half of 2008.
We are also evaluating AMG 531 in MDS and chemotherapy-induced thrombocytopenia (“CIT”). Phase 2
studies in each setting were initiated in 2006. The trials are currently ongoing and we continue to evaluate the
safety and efficacy of AMG 531 in these settings.
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