Amgen 2011 Annual Report Download - page 62

• 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, including sub-analyses, or meta-
analysis (a meta-analysis is the review of studies using various statistical methods to combine results
from previous separate but related studies) of clinical trials or clinical data performed by us or others; and
• new legislation or rules by regulatory agencies.
For example, in December 2009, based on the Trial to Reduce Cardiovascular Events with Aranesp®
Therapy (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
October 2010, we submitted additional proposed labeling changes regarding the use of ESAs in CRF patients not
on dialysis that would limit treatment to patients who are most likely to benefit, specifically those with
significant anemia (<10 g/dL), and who are at high risk for transfusion and for whom transfusion avoidance is
considered clinically important, including those in whom it is important to preserve kidney transplant eligibility.
In June 2011, we announced that the FDA had approved further changes to the labels for the use of ESAs,
including Aranesp®and EPOGEN®, in patients with CKD. (See Our ESAs continue to be under review and
receive scrutiny by regulatory authorities.)
In addition to revised labeling for our products, discovery of new safety information or previously unknown
safety concerns and/or safety signals with our products or similar products could also lead to:
• requirement of risk management activities (including a REMS) or other FDA compliance actions related
to the promotion and sale of our products;
• mandated PMCs/PMRs or pharmacovigilance programs for our approved products;
• product recalls of our approved products;
• revocation of approval for our products from the market completely, or within particular therapeutic
areas, and/or;
• increased timelines or delays in being approved by the FDA or other regulatory bodies; and
• fewer treatments or product candidates being approved by regulatory bodies.
Product safety concerns could cause regulatory agencies to impose risk management activities upon us
(including a REMS), which may require substantial costs and resources to negotiate, develop, implement and
administer. The results of these risk management activities could:
• impact the ability of healthcare providers to prescribe, dispense or use our products;
• limit patient access to our products;
• reduce patient willingness to use our products;
• place administrative burdens on healthcare providers in prescribing our products; and
• affect our ability to compete against products that do not have a REMS or similar risk management
activities.
We currently have approved REMS for our ESAs, Prolia®and Nplate®, and we use third-party service
providers to assist in the administration of our REMS that include elements to assure safe use. For example, our
ESA REMS requires applicable healthcare providers and institutions to enroll in the program, receive education
about the product and the REMS and document and report certain information to us over time. We are
responsible for tracking and documenting certain elements of healthcare provider and institution compliance with
the ESA REMS and providing the FDA with periodic assessment reports to demonstrate that the goals of the
REMS are being met. If we or third-party service providers acting on our behalf fail to effectively implement
and/or administer the REMS for our products, we may be required to modify such REMS, and we may be subject
to FDA enforcement actions or to civil penalties.
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