Amgen 2011 Annual Report Download - page 61

used endpoints other than overall survival, such as progression-free survival and bone-metastasis-free survival
(BMFS), in the clinical trial data submitted for agency review or in clinical trials now being conducted. The use
of endpoints such as progression-free survival or BMFS, in the absence of other measures of clinical benefit, may
not be sufficient for approval even when such results are statistically significant. For example, our pivotal phase
3 Study ’147 evaluated XGEVA®for its ability to improve BMFS in men with castration-resistant prostate
cancer that has not yet spread to bone. On February 8, 2012, the FDA convened the ODAC to discuss our sBLA
filing for XGEVA®to delay bone metastases in prostate cancer and the data from Study ’147 submitted to
support the filing. During its presentation to the ODAC, the FDA questioned the magnitude of the improvement
in BMFS demonstrated in Study ’147, and indicated that a further clinical trial might help address some of the
remaining unresolved questions regarding the clinical significance of the benefit achieved by XGEVA®in this
setting. The ODAC panel concluded that the magnitude of benefit demonstrated with early treatment with
XGEVA®to delay bone metastases was not sufficient to conclude a positive risk-benefit ratio for XGEVA®in
the absence of additional measures impacting quality of life or other disease outcomes. Further, some of our
products or product candidates may be used with a companion diagnostic product, such as a test kit, or
companion device, such as an injector or other delivery system. These product candidates or expanded
indications of our products may not be approved if the companion diagnostic product or companion device does
not gain or maintain regulatory approval. These companion diagnostics and devices may be provided by single-
source unaffiliated third-party companies. We are dependent on the sustained cooperation and effort of those
third-party companies in conducting the studies required for such approval by the applicable regulatory agencies.
Delays in the studies or failure of the third-party company to obtain regulatory approval of the companion
diagnostic or device could negatively impact the approval of our product candidate or the expanded indication of
our product and we may incur increased development costs, delays in regulatory approval and/or associated
delays in a product candidate reaching the market or the expansion of existing product labels for new indications.
In addition to the clinical trials that we choose to or are required to conduct, other organizations may also
conduct clinical trials that use our products. Such clinical trials may evaluate our products in areas in which we
do not have and are not seeking an approved indication. However, negative results or safety signals arising in
other organizations’ clinical trials may nonetheless prompt regulatory agencies to take regulatory actions that
affect our approved indications, including requiring the addition of relevant safety data to the approved labeling
or even withdrawing approval for our products.
The occurrence of a number of high profile safety events has caused an increased public and governmental
concern about potential safety issues relating to pharmaceutical and biological products and certain of our
products and product candidates. (See Our ESAs continue to be under review and receive scrutiny by regulatory
authorities.) As a result of this increased concern in recent years, the U.S. regulatory environment has evolved
and safety signals and safety concerns resulting from pre-clinical data, clinical trials (including sub-analyses and
meta-analyses), market use or other sources are receiving greater scrutiny. For example, a number of regulatory
agencies around the world, including the FDA and the EMA, have initiated programs to directly monitor for
safety issues rather than wait for patients, providers or manufacturers to report safety problems with products or
medical devices. And at least one private, for-profit company has begun aggregating and analyzing FDA adverse
event data on its website using its own independent methodology, which could highlight new perceived risks of
our products and product candidates. Actual or perceived safety problems or signals could lead to revised or
restrictive labeling of our approved products or a class of products, potentially including limitations on the use of
approved products in certain patients because of:
• the identification of actual or theoretical safety or efficacy concerns with respect to any of our products
by regulatory agencies;
• an increased rate or number of previously-identified safety-related events;
• the discovery of significant problems or safety signals or trends with a similar product that implicates an
entire class of products;
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