Dear Dr. Phurrough:

Amgen Inc. (Amgen) is writing regarding the
Centers for Medicare and Medicaid Services’ (CMS)
June 30, 2008, publication of and request for
comment on potential National Coverage
Determination (NCD) topics. As a science-based,
patient-driven company committed to using science
and innovation to dramatically improve people’s
lives, Amgen has always been dedicated to meeting
the very highest standards with regard to patient
safety, as well as to ensuring access to
innovative drugs and biologicals for Medicare
beneficiaries. For these reasons, we are
submitting comments on the use of erythropoiesis
stimulating agents (ESAs) to treat anemia in
patients with end-stage renal disease (ESRD),
which was among the topics included in the CMS
potential NCD topic list for the third quarter of
2008.

As the information in our separately submitted
detailed comments will indicate, we believe that
the current US Food and Drug Administration (FDA)
labeling and prescribing instructions specify the
benefits and risks of ESA therapy and instruct
providers about how to appropriately utilize ESAs
in different clinical situations. Additionally,
current CMS policies for ESAs in ESRD
appropriately enable individualized treatment of
patients in accordance with current FDA
prescribing information while imposing financial
penalties for physicians who do not appropriately
reduce ESA doses in response to hemoglobin levels
above the target range. Recent hemoglobin trend
data (through June 2008) demonstrate that
nephrologists have responded to the CMS ESA
Monitoring Policy (EMP), as well as to new
clinical data and recent label changes.
Therefore, it is unclear what additional benefits
to Medicare beneficiaries would be conferred by
any new or revised Medicare policies for ESAs in
ESRD.

Analysis of real world data suggests that
physician ESA prescribing behavior has evolved as
a result of several factors including the body of
evidence on the benefits and risks associated
with ESAs in ESRD, analysis of recent safety data
in the literature and at a joint session of the
FDA’s Cardiovascular and Renal Drugs Committee
and the Drug Safety and Risk Management Advisory
Committee (CRDAC/DSARM), the recent revisions to
FDA prescribing information for ESAs in chronic
renal failure (CRF), and the recent changes to
the CMS EMP. Key points, which are explained
further in our separately submitted detailed
comments, include the following:

• EPOGEN® (Epoetin alfa), first approved by
the FDA in 1989, revolutionized the care of
dialysis patients with anemia by dramatically
reducing the need for red blood cell transfusions
and improving patient reported outcomes.
• ESAs are safe and effective when used in
accordance with FDA labeling.
• Current product labeling, updated in 2007
after important questions on safety and
appropriate use of ESAs in patients with kidney
disease were raised, reflects the affirmation of
the FDA and its advisory committees of the
positive risk benefit profile of ESAs in chronic
renal failure when dosing is individualized to
achieve and maintain a hemoglobin concentration
in the range of 10 to 12 grams per deciliter
(g/dL).
• It has been recognized that safety
concerns associated with ESAs in ESRD may be the
result of targeting higher hemoglobin values
particularly in hyporesponsive patients, and thus
important information regarding appropriate
hemoglobin range and dosing modifications have
been implemented in the FDA prescribing
instructions to address this.
• Anemia management and appropriate
utilization of ESAs in dialysis patients have
been CMS priorities since the 1990s. Current CMS
policies, including Clinical Performance Measures
(CPMs), ESA coverage policy, and the ESA
Monitoring Policy (EMP) effectively support FDA
prescribing information.
• Data show that nephrologists have
responded to safety concerns, the new label, and
recent CMS EMP revisions with improved hemoglobin
management of dialysis patients.
• It is unclear what additional benefits to
Medicare beneficiaries would be conferred by any
new or revised Medicare policies for ESAs in
dialysis.

Amgen appreciates this opportunity to provide
important information and looks forward to
working with you to ensure that Medicare
beneficiaries continue to have appropriate to
important therapies. Please contact Sarah Wells
Kocsis by phone at (202) 585-9713 or by email at
wellss@amgen.com to arrange a meeting or if you
have any questions regarding our response. Thank
you for your attention to this important matter.

Regards,

Joshua J. Ofman, MD, MSHS
Vice President,
Global Coverage and Reimbursement and Global
Health Economics