Amgen 2007 Annual Report Download - page 53

use in oncology. Responding to questions posed by the FDA, the ODAC recommended that more restrictions be
added to ESA labels and that additional clinical trials be conducted by companies with currently approved ESAs,
including us, although no specific restrictions or studies were recommended at the ODAC meeting. The commit-
tee is advisory and FDA officials are not bound to or limited by its recommendations. However, the FDA has
commonly followed the recommendations of its advisory panels. Although not required, the FDA has and will
likely continue to take into consideration the recommendations by the ODAC in its ongoing discussions with us
regarding our ESAs. The FDA also 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.
On November 8, 2007, in recognition of the input from the May 2007 ODAC and September 2007 joint
CRDAC/DSaRMAC meetings, we announced additional updates to the Aranesp®and EPOGEN®/PROCRIT®
package inserts which reflected ongoing interactions with the FDA regarding the safety and benefit/risk profile of
ESAs. The changes to the ESA labels included modifications to the boxed warnings which included language
with respect to renal failure which stated that “patients experienced greater risks for death and serious car-
diovascular events when administered ESAs to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL;
14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the
range of 10 to 12 g/dL.” The boxed warning for the cancer indication was updated to describe studies in patients
with advanced breast, head and neck, lymphoid and NSCLC malignancies and stated that “the risks of shortened
survival and tumor promotion have not been excluded when ESAs are dosed to target a hemoglobin of less than
12 g/dL. To minimize these risks as well as the risk of serious cardio- and thrombovascular events, use the lowest
dose needed to avoid red blood cell transfusions.” Additional language was also added to the INDICATIONS
AND USAGE section, and the WARNINGS section and clarification of the Hb range for CRF patients was add-
ed in the DOSAGE AND ADMINISTRATION section. In addition, we are working with the FDA to design a
large, definitive, well controlled study comparing the safety of ESAs administered to a maximum Hb target of 12
g/dL per the product labeling versus placebo in three major tumor types (NSCLC, breast cancer and advanced
CRC). We have agreed on the general study design, and plan to submit a study protocol after obtaining guidance
from ODAC. We and J&JPRD are in discussions with the FDA as to any additional studies that will be required
to address remaining concerns in other disease settings. (See “Item 1. Business — Postmarketing and Safety
Activities.”) The addition of these clinical trials to our pharmacovigilance program and any additional clinical
trials required by the FDA could result in substantial additional expense, additional label restrictions, or the loss
of regulatory approval for an approved indication and may have a material adverse effect on our business and re-
sults of operations. Additionally, any negative results from such trials could materially affect the extent of
approvals, the use, reimbursement and sales of our ESA products. (See “— Before we commercialize and sell any
of our product candidates, we must conduct clinical trials in humans; if we fail to adequately manage these trials
we may not be able to sell future products and our sales could be adversely affected.”)
We continue to work closely with the FDA to complete further labeling revisions to the class of ESAs, in-
cluding Aranesp®and EPOGEN®. We are in discussions with the FDA regarding safety data from the PREPARE
and GOG-191 studies including an updated box warning in the labeling information. These proposed labeling
changes were submitted under the regulatory mechanism known as the CBE process. We continue to work close-
ly with the FDA to complete further revisions to our ESA labels including proposed revisions to the product
labeling we submitted to the FDA in December 2007 that addressed questions raised during the May 2007
ODAC meeting regarding Hb initiation, Hb ceiling, discontinuation of ESA therapy after chemotherapy and data
from additional clinical studies.
Additionally, the FDA has scheduled an ODAC meeting on March 13, 2008, as part of the ongoing pharma-
covigilance review of ESAs. Although we cannot predict what additional action the FDA may require of us or
what recommendations may arise from the March 13th ODAC meeting, further revisions to the labels for Ara-
nesp®and EPOGEN®could have a material adverse impact on the reimbursement, use and sales for our ESA
products, 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
of our products and we may be required to perform additional clinical trials or change the labeling of our prod-
ucts or take other potentially limiting or costly actions if we or others identify side effects after our products are
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