Amgen 2009 Annual Report Download - page 47

Dulanermin (rhApo2L/TRAIL)
Dulanermin is a recombinant human protein that targets death receptors 4 (“DR4”) and DR5 and induces
apoptosis in sensitive tumor cells. It is being investigated as a cancer treatment. We are developing this molecule
in collaboration with Genentech, Inc., a wholly owned member of the Roche Group.
Phase 2 data from the non-Hodgkin’s Lymphoma and NSCLC studies have been analyzed and we plan to
present the results at an upcoming medical meeting.
Denosumab
Denosumab is a fully human monoclonal antibody that specifically targets a ligand known as RANKL (that
binds to a receptor known as RANK) which is a key mediator of osteoclast formation, function and survival. De-
nosumab is being studied across a range of conditions including osteoporosis, treatment-induced bone loss, bone
metastases, multiple myeloma and RA.
The overall denosumab program remains on track with all completed phase 3 trials for denosumab having
met all primary endpoints. The following chart is an overview of the phase 3 clinical development program for
denosumab:
Program Area Indication
Enrollment
Status Projected Data Availability
Osteoporosis PMO Treatment (versus placebo) Complete Received
Osteoporosis PMO Treatment (versus ALN) Complete Received
Osteoporosis PMO Prevention Complete Received
Osteoporosis PMO Transition (from ALN) Complete Received
Osteoporosis Male Osteoporosis Enrolling 2012
Oncology Treatment-Induced Bone Loss-Prostate Cancer Complete Received
Oncology Treatment-Induced Bone Loss-Breast Cancer Complete Received
Oncology Bone Metastases-Prostate Cancer Complete 2010(1)
Oncology Bone Metastases-Breast Cancer Approved TBD(2)
Oncology Skeletal-Related Events-Breast Cancer Complete Received
Oncology Skeletal-Related Events-Solid Tumors/multiple myeloma Complete Received
Oncology Skeletal-Related Events-Prostate Cancer Complete Received
(1) Event-driven study and consequently data availability may vary as a result
(2) TBD = to be determined
In 2009, we announced that a pivotal, phase 3, head-to-head trial evaluating denosumab versus Zometa®in
the treatment of bone metastases in 2,046 patients with advanced breast cancer met its primary endpoint (non-
inferiority compared to Zometa®) and secondary endpoints (superiority compared to Zometa®). Superior efficacy
compared to Zometa®was demonstrated for both delaying the time to the first on-study SREs (fracture, radiation
to bone, surgery to bone or spinal cord compression) (HR: 0.82 [95% CI 0.71 - 0.95]), and delaying the time to
the first-and-subsequent SREs (HR: 0.77 [95% CI 0.66 - 0.89]). Both results were statistically significant in this
34 month study. The median time to first on-study SRE was not reached for denosumab and therefore could not
be estimated. The median time to first on-study SRE was 26.5 months for Zometa®, the current standard of care.
Overall, the incidence of adverse events and serious adverse events was consistent with what has previously been
reported for these two agents. Of note, osteonecrosis of the jaw (“ONJ”), which had not been observed in pre-
viously reported phase 3 studies with denosumab, was seen infrequently in both treatment groups (20 patients
receiving denosumab as compared with 14 patients receiving Zometa®). There was no statistically significant
difference in the rate of ONJ between the two treatment arms. Infectious adverse events were balanced between
the two treatment arms, as was OS and the time to cancer progression.
In 2009, we also announced that a pivotal, phase 3, head-to-head trial evaluating denosumab administered
subcutaneously versus Zometa®administered as an intravenous infusion in the treatment of bone metastases in
1,776 advanced cancer patients with solid tumors (not including breast and prostate cancer) or multiple myeloma
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