Amgen 2009 Annual Report Download - page 48

met its primary endpoint. For the primary endpoint of this study, the median time to first on-study SRE (fracture,
radiation to bone, surgery to bone or spinal cord compression) was 20.6 months for those patients receiving
denosumab and 16.3 months for those patients receiving Zometa®(HR: 0.84, 95% CI: 0.71-0.98), which is stat-
istically significant for non-inferiority (p=0.0007). Although numerically greater, the delay in the time to first
SRE associated with denosumab was not statistically superior compared to Zometa®based upon the statistical
testing strategy (adjusted p=0.06) (secondary endpoint). The time to first-and-subsequent SRE was also numeri-
cally greater but not statistically superior compared to Zometa®(HR: 0.90 [95% CI 0.77 - 1.04]) (secondary
endpoint). Overall, the incidence of adverse events and serious adverse events was consistent with what has pre-
viously been reported for these two agents. Rates of ONJ were balanced and infrequent in both treatment groups
(10 patients receiving denosumab as compared with 11 patients receiving Zometa®). Infectious adverse events
were balanced between the two treatment arms, as was OS and the time to cancer progression.
On February 8, 2010, we announced that a pivotal, phase 3, head-to-head trial evaluating denosumab versus
Zometa®in the treatment of bone metastases in 1,901 men with advanced prostate cancer met its primary end-
point of non-inferiority in time to first SRE and its secondary endpoints (superiority compared to Zometa®for
both delaying the time to the first on-study SRE and delaying the time to the first-and-subsequent SREs).
Denosumab demonstrated superiority over Zometa®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 de-
laying the time to the first-and-subsequent SREs (HR: 0.82 [95% CI 0.71 - 0.94]). Both results were statistically
significant. Overall rates of adverse events and serious adverse events, including infections, were generally sim-
ilar between the two arms. ONJ was infrequent (22 patients receiving denosumab as compared with 12 patients
receiving Zometa®) and there was no statistically significant difference between treatment arms. As with pre-
vious studies in advanced cancer patients, hypocalcemia was more frequent in the denosumab arm. Both OS and
the time to cancer progression were balanced between treatment arms.
The phase 3 ‘147 study evaluating denosumab in patients with non-metastatic prostate cancer to prevent
bone metastases is ongoing. We expect to receive the results from this study the second half of 2010.
Motesanib
Motesanib is an orally-administered small molecule antagonist of vascular endothelial growth factor re-
ceptors 1, 2 and 3, platelet-derived growth factor receptor and stem cell factor receptor. It is being investigated as
a cancer treatment. We are developing this product in collaboration with Takeda.
Enrollment in the phase 3 first-line NSCLC study (MONET1) evaluating motesanib in combination with
paclitaxel and carboplatin for the first-line treatment of advanced NSCLC is nearly complete. Based on current
event rates, we anticipate completion of the study in 2011.
In April 2009, Amgen and Millennium announced the phase 2 trial in metastatic breast cancer has been com-
pleted and the results support continued development.
Nplate®(romiplostim)
Nplate®is a peptibody agonist of the TPO receptor.
Nplate®is the first FDA-approved agent that acts directly to increase platelet production for the treatment of
thrombocytopenia in splenectomized (spleen removed) and non-splenectomized adults with chronic ITP, who
have had an insufficient response to corticosteroids, immunoglobulins or splenectomy.
In December 2009, we announced results from its first phase 1/2 study evaluating the safety and efficacy of
Nplate®in children with chronic ITP. Results of the study showed that treatment with Nplate®appeared to be
generally well-tolerated compared to placebo in children (aged 12 months to less than 18 years old) with chronic
ITP (treatment related adverse events = 18% versus 20%, respectively).
In addition, we announced results from three studies on the safety and efficacy of Nplate®in adult patients
with myelodysplastic syndromes (“MDS”). Data from two separate phase 2 studies showed that patients with low
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