Amgen 2007 Annual Report Download - page 51

and Commerce and the United States Senate Committee on Finance with inquiries with respect to our ESA stud-
ies, promotions of our ESA and our pharmacovigilance program to which we have fully cooperated by
submitting our responses and meeting with Congressional staff. To the extent that there is resulting legislation or
changes in CMS or FDA policy as a result of Congressional concerns, such changes could have a material or ad-
verse effect on the use of our ESA products.
As a result of this increasing concern, potential or perceived safety signals and safety concerns, from clinical
trials, use by the market or other sources, are receiving greater scrutiny, which may lead to fewer treatments be-
ing approved by the FDA or other regulatory bodies, revised labeling of an approved product or a class of
products for safety reasons, potentially including a boxed warning or additional limitations on the use of ap-
proved products in specific therapeutic areas (until additional clinical trials can be designed and completed),
mandated PMCs, pharmacovigilance programs for approved products or requirement of risk management activ-
ities related to the promotion and sale of a product. In addition, significant concerns about the safety and
effectiveness of our products could ultimately lead to the revocation of marketing approval by therapeutic area,
or in total, which would have a material adverse effect on the use, sales and reimbursement of the affected prod-
ucts and on our business and results of operations. (See “— Our sales depend on payment and reimbursement
from third-party payers, and, to the extent that reimbursement for our products is reduced, this could negatively
impact the utilization of our products.”)
Certain specific labeling or label changes of approved products or product candidates may be necessary or
required for a number of reasons, including: the identification of actual or theoretical safety or efficacy concerns
by regulatory agencies, the discovery of significant problems with a similar product that implicates an entire
class of products, subsequent concerns about the sufficiency of the data or studies underlying the label or changes
to the underlying safety/efficacy analysis related to results from clinical trials performed by us or others. In addi-
tion, before or after any of our products are approved for commercial use, regulatory bodies could decide that the
product labels need to include certain warning language as part of an evolving label change to a particular class
of products. For example, in March and November 2007, the labels of the class of ESA products, including Ara-
nesp®and EPOGEN®, were updated to include revised boxed warnings, restrictions on the use of ESAs in
specific therapeutic areas and other safety-related product labeling changes. We continue to be in discussion with
the FDA to complete further revisions to our ESA labels. (See “— Recent labeling updates to our ESAs and po-
tential future labeling changes or recommendations from the upcoming March 13, 2008 ODAC meeting may
adversely impact the use, sales and reimbursement of our ESAs.”) The FDA previously instituted a class label
change for the class of ESAs to add information about pure red cell aplasia (“PRCA”) to the adverse event profile
section and for the boxed warning in the prescribing information of the label described above. A revision of
product labeling or the regulatory actions described above could be required even if there is no clearly estab-
lished connection between the product and the safety or efficacy concerns that have been raised. Also in October
2007, we announced that we and the FDA adopted changes to the U.S. prescribing information for Vectibix™
based on the results of the PACCE trial highlighting to clinicians the greater risk seen when Vectibix™ is com-
bined with Avastin®and the specific chemotherapy used in the PACCE trial to treat patients with first-line
mCRC. Vectibix™ is not indicated for the first-line treatment of mCRC and the new safety information applies
to an unapproved use of Vectibix™. Additionally, we are in discussions with the FDA with respect to the class of
TNF inhibitor agents around several safety issues, which may result in additional patient safety information in
the form of a boxed warning that will apply to the ENBREL label as has been the case with other TNF inhibitor
agents.
In addition, if we or others identify safety concerns before approval of the product or after a product is on
the market, the regulatory agencies such as the FDA or EMEA may impose risk management activities upon us
and/or may require additional or more extensive clinical trials as part of PMCs or a pharmacovigilance program
prior to the marketing approval of our product or for approval of a new indication for a marketed product, any of
which could have a material adverse effect on sales of the affected products and on our business and results of
operations. Regulatory agencies such as the FDA could require us to engage in risk management activities,
possibly including a REMS, which could modify or restrict our existing promotional activities, restrict or
encumber the ability of healthcare providers to prescribe, dispense or use our products or limit patient access to
our products. In addition to our ESA products, we have ongoing PMC studies for substantially all of our
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