Amgen 2012 Annual Report Download - page 49

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Some of our products are used with drug delivery or companion diagnostic devices which have their own regulatory,
manufacturing, reimbursement and other risks.
Some of our products or product candidates may be used in combination with a drug delivery device, such as an injector or
other delivery system. Our product candidates or expanded indications of our products used with such drug delivery devices may
not be approved or may be substantially delayed in receiving regulatory approval if such devices do not gain or maintain regulatory
approval or clearance. Where approval of the product and device is sought under a single marketing drug application, the increased
complexity of the review process may also delay receipt of regulatory approval. In addition, some of these drug delivery 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 both to supply the devices and, in some cases, to conduct the studies required for approval or
clearance by the applicable regulatory agencies. We are also dependent on those third-party companies continuing to meet the
applicable regulatory and other requirements to maintain that approval or clearance once it has been received. Failure to supply
the devices, delays in or failure of the Amgen or third-party studies, or failure of the third-party company to obtain or maintain
regulatory approval or clearance of the devices could result in increased development costs, delays in or failure to obtain regulatory
approval and/or associated delays in a product candidate reaching the market or the expansion of existing product labels for new
indications. Loss of regulatory approval or clearance of a device that is used with our product may also result in the removal of
our product from the market.
Similarly, some of our products or product candidates may be used in combination with an in vitro companion diagnostic
device, such as a test kit. In some cases, our product candidates or expanded indications of our products used with in vitro companion
diagnostic devices may not be approved or may be substantially delayed in receiving regulatory approval if such devices do not
gain or maintain regulatory approval or clearance. For example, the FDA has informed us that its approval of Vectibix® for the
first- and second-line mCRC indications we are seeking will be contingent upon approval of the companion diagnostic device
being developed in collaboration with QIAGEN, which identifies a patient's KRAS gene status. As with drug delivery devices used
with our products, our ability to get and maintain the necessary regulatory approvals for our products or product candidates used
with in vitro companion diagnostic devices can be substantially dependent on whether the manufacturers of such devices meet
their contractual responsibilities to us and/or their obligations to regulatory authorities. Failures by these manufacturers can also
result in the significant delays and added costs described above, or even result in the removal of our product from the market.
The in vitro companion diagnostic and drug delivery devices used with our products are also subject to many of the same
reimbursement risks and challenges to which our products are subject. (See Our sales depend on coverage and reimbursement
from third-party payers.) A reduction in the availability of, or the coverage and/or reimbursement for, in vitro companion diagnostic
or drug delivery devices used with our products could have a material adverse effect on our product sales, business and results of
operations.
Our ESAs continue to be under review and receive scrutiny by regulatory authorities.
Beginning in 2006, adverse safety results involving ESAs were observed and since that time our ESAs have been the subject
of ongoing review and scrutiny by regulatory authorities and other agencies. In the United States, over this time frame the FDA
has reviewed the benefit-risk profile of ESAs, which has resulted in changes to ESA labeling and usage in both the oncology and
nephrology clinical settings. Over this same time period, CMS has also evaluated the use of ESAs and has made substantial
reimbursement changes in the oncology and nephrology clinical settings. (See Our sales depend on coverage and reimbursement
from third-party payers.) Together, these labeling and reimbursement changes, along with the approved REMS for ESAs, have
had and may continue to have a material adverse effect on sales of our ESAs, our business and results of operations, and further
labeling or reimbursement changes by these regulatory authorities could increase the severity of that effect.
We have also agreed with the FDA to conduct a number of PMCs for our ESAs. In 2004, we agreed with the FDA to a robust
pharmacovigilance program to continue to study the safety surrounding the use of darbepoetin alfa in the oncology setting. Of the
five studies originally included in that pharmacovigilance program, four are complete and analysis of the results from the fifth
study, LHN03-6B, is currently ongoing. The results of certain of those studies contributed to safety-related product labeling changes
for our ESAs and changes in reimbursement, as noted above. Other trials have subsequently been initiated to inform on the safety
of ESAs. In 2009 we initiated Study '782, a phase 3 non-inferiority study evaluating overall survival when comparing NSCLC
patients on Aranesp® to patients receiving placebo, as part of our Aranesp® pharmacovigilance program. In addition, JRD's EPO-
ANE-3010 study, which evaluates the use of epoetin alfa in patients with breast cancer, is ongoing. Both of these studies are
designated by the FDA as PMRs and must be conducted to maintain regulatory approval and marketing authorization. For the
nephrology setting, we have been engaged in ongoing discussions with the FDA regarding additional PMRs to explore alternative
ESA dosing strategies in CKD patients on dialysis and not on dialysis. In July 2012 we initiated study '226 to evaluate Aranesp®
use in CKD patients not on dialysis. We expect to discuss further with the FDA another potential study in CKD patients on dialysis.
Although we cannot predict the results or the outcomes of ongoing clinical trials, or the extent to which regulatory authorities may