Amgen 2007 Annual Report Download - page 28

• The starting dose for ESA treatment is the recommended FDA label starting dose, no more than 150 unit
(“U”)/kilogram (“kg”)/three times weekly for Epoetin and 2.25 mcg/kg/weekly for darbepoetin alfa.
Equivalent doses may be given over other approved time periods;
• Maintenance of ESA therapy is the starting dose if the Hb level remains below 10 g/dL (or hematocrit is
< 30%) 4 weeks after initiation of therapy and the rise in Hb is > 1 g/dL (hematocrit > 3%). However, if
after the first 4 weeks the Hb is > 10 g/dL, ESA treatment is not covered;
• For patients whose Hb rises < 1 g/dL (hematocrit rise < 3%) compared to pretreatment baseline over 4
weeks of treatment and whose Hb level remains < 10 g/dL after the 4 weeks of treatment (or the hema-
tocrit is < 30%), the recommended FDA label starting dose may be increased once by 25%. Continued
use of the drug is not reasonable and necessary if the Hb rises < 1 g/dL (hematocrit rise < 3 %) compared
to pretreatment baseline by 8 weeks of treatment;
• Continued administration of the drug is not reasonable and necessary if there is a rapid rise in Hb > 1 g/
dL (hematocrit > 3%) over 2 weeks of treatment unless the Hb remains below or subsequently falls to <
10 g/dL (or the hematocrit is < 30%). Continuation and reinstitution of ESA therapy must include a dose
reduction of 25% from the previously administered dose; and
• ESA treatment duration for each course of chemotherapy under the above conditions includes the eight
weeks following the final dose of myelosuppressive chemotherapy in a chemotherapy regimen.
Under the provisions of the Decision Memorandum, Medicare contractors may continue to issue local cover-
age determinations based on the existing Medicare policy of “reasonable and necessary determinations” on all
uses of ESAs that are not determined by the Decision Memorandum, including myelodysplastic syndrome
(“MDS”).
The Decision Memorandum establishes the ESA reimbursement policy for Medicare and other government
beneficiaries who are treated for CIA and who all together accounted for approximately 50% of the U.S. cancer
patients receiving Aranesp®prior to its issuance. We believe that the majority of CIA patients who received
treatment with ESAs, including Aranesp®, were initiated at Hb levels above 10 g/dL and were maintained with
Hb levels above 10 g/dL with continued therapy prior to the issuance of the Decision Memorandum. Given that
the Decision Memorandum contains a coverage restriction for Hb levels greater than 10 g/dL, we believe that
such restriction has and will continue to change the way ESAs are used in clinical practice, for example, by de-
creasing the number of treated patients, the average ESA dose and the duration of ESA therapy.
We believe this restriction on reimbursement of ESAs in the Decision Memorandum has had and will con-
tinue to have a material adverse effect on the use, reimbursement and sales of Aranesp®, and our business and
results of operations. Additionally, based on our knowledge, although no private payers have implemented the
Decision Memorandum to date, many private payers have implemented the Hb initiation restriction included in
the Decision Memorandum. Further, due to difficulties in administering a two-tier medical practice, we believe
many healthcare providers have reduced ESA utilization for all of their patients regardless of insurance coverage.
Also, although the Decision Memorandum did not directly affect reimbursement for treatment of MDS, we also
believe that certain physicians have reduced ESA utilization in this setting. While we cannot fully predict the
impact of the Decision Memorandum on how, or under what circumstances, healthcare providers will prescribe
or administer our ESAs, it had a significant impact to our business in 2007 and believe that it will significantly
impact us in 2008.
In addition, the FDA held a joint meeting of the CRDAC and the DSaRMAC on September 11, 2007, which
evaluated the safety data on ESA use in renal disease. Although CMS has made no announcement of a nephrol-
ogy focused national coverage analysis (“NCA”), any NCD for ESAs in the renal setting, which may include
non-coverage and/or new dosing and treatment restrictions similar to those proposed in Decision Memorandum
for treatment of anemia in oncology with ESAs, would negatively affect use, reduce reimbursement and cover-
age, negatively affect product sales of our ESA products and may have a material adverse effect on our business
and results of operations.
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