Amgen 2009 Annual Report Download - page 53

ies; (ii) mandate labeling changes to products and (iii) require sponsors to implement a REMS for a product. Fail-
ure to comply with FDAAA requirements could result in significant civil monetary penalties, reputational harm
and increased product liability risk. We are unable to predict when and whether any changes to regulatory policy
affecting our business could occur, and such changes could have a material adverse impact on our business.
Obtaining and maintaining regulatory approval has been and will continue to be increasingly difficult, time-
consuming and costly. For example, in October 2009 we received Complete Response Letters from the FDA for
the BLA for our late-stage product candidate ProliaTM in the treatment and prevention of PMO and in the treat-
ment and prevention of bone loss due to HALT in breast and prostate cancer patients. The Complete Response
Letter related to the PMO indication requested several items, including further information on the design and
background adverse event rates that will inform the methodology of our previously submitted post-marketing
surveillance program. The FDA also requested a new clinical program to support approval of ProliaTM for the
prevention of PMO, updated safety data and stated that a REMS is necessary for ProliaTM. The Complete Re-
sponse Letter related to the HALT indication requested additional information regarding the safety of ProliaTM in
patients with breast cancer receiving aromatase inhibitor therapy and patients with prostate cancer receiving
ADT. The FDA specifically requested results from additional adequate and well-controlled clinical trials demon-
strating that ProliaTM has no detrimental effects on either time to disease progression or OS. On February 19,
2010, we announced that the FDA has evaluated the content of our Complete Response submission for ProliaTM
in the treatment of PMO, which we submitted on January 25, 2010, and classified it as a Class 2 resubmission.
With the Class 2 designation, the FDA set a corresponding PDUFA action date of July 25, 2010. A significant
delay in regulatory approval to market and sell ProliaTM for the treatment of PMO could have a material adverse
affect on our business and results of operations.
In addition, some of our products are approved by U.S. and foreign regulatory authorities on a conditional
basis with full approval conditioned upon fulfilling requirements of regulators. Vectibix®, for example, received
conditional approval in the United States and EU, with final approval conditioned on conducting additional clin-
ical trials of the use of Vectibix®as a therapy in treating mCRC. Our conditional approval of Vectibix®in the
EU was received in December 2007 and is reviewed annually by the CHMP and in December 2008 and 2009 we
received renewal of the conditional approval subject to us completing an additional clinical trial in the existing
approved indication. In 2009, the CHMP approved our protocol for this additional clinical trial, which will com-
pare the effect of Vectibix®versus Erbitux®on OS for chemorefractory mCRC patients with wild-type KRAS
tumors. 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
these 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 com-
panion 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, asso-
ciated delays in a product candidate reaching the market or the expansion of existing product labels for new
indications.
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 prod-
ucts and product candidates. (See “— Our ESA products continue to be under review and receive scrutiny by
regulatory authorities.”) As a result of this increased concern, safety signals and safety concerns resulting from
clinical trials (including sub-analyses and meta-analyses), market use or other sources are receiving greater scru-
tiny. Actual or perceived safety problems could lead to significant revised or restrictive labeling of our approved
products or a class of products, potentially including limitations on the use of approved products in certain pa-
tients because of:
• the identification of actual or theoretical safety or efficacy concerns with respect to any of our products
by regulatory agencies
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