Amgen 2009 Annual Report Download - page 55

approve the product candidate or new indication or maintain approval of the current indication in its current form
or at all, and we would not be able to market and sell it. If we were unable to market and sell our products or
product candidates, our business and results of operations would be materially and adversely affected. Further,
safety signals, trends, adverse events or results from clinical trials or studies performed by us or by others
(including our licensees or independent investigators) from the marketed use of our drugs that result in revised
safety-related labeling or restrictions on the use of our approved products could negatively impact healthcare
provider prescribing behavior, use of our products, regulatory or private health organization medical guidelines
and reimbursement for our products all of which would have a material adverse effect on our business and results
of operations.
Our ESA products continue to be under review and receive scrutiny by regulatory authorities.
Beginning in 2006, adverse safety results involving ESA products were observed and since that time our
ESAs have been the subject of ongoing review and scrutiny from regulatory authorities. In the United States, the
FDA continues to review the benefit-risk profile of ESAs, which have resulted and could result in future changes
to ESA labeling and usage. For example, we revised the labeling for our ESAs in August 2008, as the FDA di-
rected, and since that time have experienced a reduction in our ESA sales, in particular Aranesp®sales in the
U.S. supportive cancer care setting. In October 2009, the results from TREAT, a phase 3 pivotal study of patients
with CKD not on dialysis were published in the New England Journal of Medicine. The study failed to meet its
primary objectives of demonstrating a reduction in all-cause mortality, cardiovascular morbidity, including heart
failure, heart attack, stroke or hospitalization for myocardial ischemia, or time to ESRD. On December 16, 2009,
based on the TREAT results, we updated the boxed warning in the labeling information for ESAs, to reflect an
increased risk of stroke when ESAs are administered to CRF patients to target Hb levels of 13 g/dL and above. In
an editorial published in the New England Journal of Medicine in January 2010, the FDA announced that it will
call an advisory committee meeting in 2010 to re-evaluate the use of ESAs to treat anemia in patients with CKD
and could consider lowering targeted Hb levels. In addition, CMS has scheduled a MEDCAC meeting for March
24, 2010 to examine currently available evidence on the use of ESAs to manage anemia in patients who have
CKD, which may consider the results from the TREAT study. The FDA may also require that we update the
REMS for ESAs based on the TREAT results. Although we cannot predict what impact all of these activities
could have on our business, the revised ESA labeling or any future labeling changes, including any required in
connection with the scheduled advisory committee meeting, our ongoing discussions with the FDA regarding the
conversion of the format of our ESA U.S. labels in accordance with the PLR or other changes required by the
FDA, the outcome from the MEDCAC meeting or the impact of the approved REMS for ESAs could have a
material adverse impact on the coverage, reimbursement and sales of our ESAs, which would have a material
adverse effect on our business and results of operations. (See “— Our current products and products in
development cannot be sold if we do not gain or maintain regulatory approval.” and “Our sales depend on
coverage and reimbursement from third-party payers.”)
We also have ongoing PMC studies for our ESAs which must be conducted to maintain regulatory approval
and marketing authorization. We have agreed with the FDA to a robust pharmacovigilance program to continue
to study the safety surrounding the use of ESAs in the oncology setting and we initiated Study 782 as part of our
Aranesp®pharmacovigilance program, a phase 3 non-inferiority study evaluating OS when comparing NSCLC
patients on Aranesp®to patients receiving placebo. We are currently identifying clinical sites for Study 782 and
have begun enrolling patients in the study. Further, in 2008 the FDA and EMA reviewed interim results from the
Preoperative Epirubicin Paclitaxel Aranesp®(“PREPARE”) study in neo-adjuvant breast cancer, a PMC study,
which were ultimately incorporated into the ESA labeling in both the United States and the EU. We received the
final results from the PREPARE study in 2009, which were substantially consistent with the interim results, and
provided that data to the FDA and EMA. Although we cannot predict the results or the outcomes of ongoing clin-
ical trials, or the extent to which regulatory authorities may require additional labeling changes as a result of
these or other trials, we cannot exclude the possibility that adverse results from clinical trials, including PMCs,
could have a material adverse impact on the reimbursement, use and sales of our ESAs, which would have a
material adverse effect on our business and results of operations.
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