Amgen 2009 Annual Report Download - page 56

Regulatory authorities outside the United States have also reviewed and scrutinized the use of our ESA prod-
ucts. In June 2008, the EMA recommended updating the product information for ESAs with a new warning for
their use in cancer patients, which was approved by the European Commission in October 2008. The product in-
formation for all ESAs was updated to advise that in some clinical situations blood transfusions should be the
preferred treatment for the management of anemia in patients with cancer and that the decision to administer
ESAs should be based on a benefit-risk assessment with the participation of the individual patient. Since the Oc-
tober 2008 revision, we have experienced a reduction of Aranesp®sales in the supportive cancer care setting in
the EU and, although we cannot predict what further impact the revised EU ESA product information could have
on our business, the reimbursement, use and sales of Aranesp®in Europe could further be materially adversely
affected, which would have a material adverse effect on our business and results of operations.
Moreover, we continue to receive results from meta-analyses or previously initiated clinical trials using
ESAs, including PMCs, and adverse results could negatively impact the use and sales of our ESAs. For example,
in September 2008, we announced that we had received a summary of preliminary results from the Cochrane
Collaboration’s independent meta-analysis of patient-level data from previously conducted, randomized, con-
trolled, clinical studies evaluating ESAs in cancer patients which we submitted to the FDA and the EMA. This
Cochrane meta-analysis of patient-level data from previous studies corroborates prior analyses indicating that the
use of ESAs may increase the risk of death in cancer patients. The studies in the analysis all predate the current
label, which advises using the least amount of ESA necessary to avoid transfusion but they do not exclude the
potential for adverse outcomes when ESAs are prescribed according to the current label.
We must conduct clinical trials in humans before we can commercialize and sell any of our product candi-
dates or existing products for new indications.
Before we can sell any products, we must conduct clinical trials to demonstrate that our product candidates
are safe and effective for use in humans. The results of these clinical trials are used as the basis to obtain regu-
latory approval from regulatory authorities such as the FDA.(See — “Our current products and products in
development cannot be sold if we do not gain or maintain regulatory approval.”) We are required to conduct
clinical trials using an appropriate number of trial sites and patients to support the product label claims. The
length of time, number of trial sites and patients required for clinical trials vary substantially and therefore, we
may spend several years and incur substantial expense in completing certain clinical trials. Delays in planned
clinical trials can result in increased development costs, delays in regulatory approvals, associated delays in
product candidates reaching the market and revisions to existing product labels. For example, in 2006 we delayed
the start of our phase 3 trial in first-line NSCLC due to an increased frequency of cholecystitis (inflammation of
the gall bladder) in patients treated with our late-stage product candidate motesanib. Following initiation of the
trial in November 2008, enrollment in this phase 3 trial was temporarily suspended following a planned safety
data review of 600 patients by the study’s independent DMC. In February 2009, the DMC recommended the trial
resume enrollment of patients with non-squamous NSCLC only, and in June 2009, we reinitiated enrollment in
this patient population following an FDA-approved revision to the study protocol.
In addition, in order to increase the number of patients available for enrollment for our clinical trials, we
have and will continue to open clinical sites and enroll patients in a number of new geographic locations where
our experience conducting clinical trials is more limited, including Russia, India, East Asia and some Central and
South American countries either through utilization of third-party contract clinical trial providers entirely or in
combination with local staff. Conducting clinical trials in locations where we have limited experience requires
substantial time and resources to identify and understand the unique regulatory environments of individual coun-
tries. If we fail to adequately manage the design, execution and regulatory aspects of our large, complex and
regulatory diverse clinical trials, corresponding regulatory approvals may be delayed or we may fail to gain ap-
proval for our product candidates or could lose our ability to market existing products in certain therapeutic areas
or altogether. If we are unable to market and sell our product candidates or are unable to obtain approvals in the
timeframe needed to execute our product strategies, our business and results of operations would be materially
adversely affected. Additional information on our clinical trials can be found on our website at www.amgen.com.
(This website address is not intended to function as a hyperlink, and the information contained on our website is
not intended to be a part of this filing.)
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