Amgen Announces Updates to the U.S. Prescribing Information for ESAs
Revised Class Labeling Based on Data Discussed at the May 2007
ODAC and September 2007 CRDAC Meetings
Six Additional Studies Added to Current Pharmacovigilance Program
THOUSAND OAKS, Calif.--(BUSINESS WIRE)--Nov. 8, 2007--Amgen
(NASDAQ:AMGN) today announced that it has updated the Aranesp(R)
(darbepoetin alfa) and EPOGEN(R)/PROCRIT(R) (Epoetin alfa) package
inserts in collaboration with the U.S. Food and Drug Administration
(FDA) and Johnson and Johnson Pharmaceutical Research & Development
(J&JPRD). The changes to the labeling include modifications to the
boxed warnings, additional language in the INDICATIONS AND USAGE
section, addition of an oncology study to the WARNINGS section, and
clarification of the hemoglobin range for chronic renal failure (CRF)
patients in the DOSAGE AND ADMINISTRATION section.
The Company also announced that it has developed a comprehensive
clinical study pharmacovigilance program designed to address
outstanding questions about ESA safety in both investigational and
labeled settings. Six new proposed clinical trials have been designed
to assess the safety of erythropoiesis-stimulating agents (ESAs) when
used to treat chemotherapy-induced anemia in specific tumor types.
Upon FDA agreement, these studies will be added to the ongoing
pharmacovigilance program, which was agreed to with the FDA after the
2004 Oncologic Drug Advisory Committee (ODAC) meeting.
"Amgen has been working closely with the FDA and J&JPRD to ensure
that the information contained in the approved labeling for ESAs
accurately reflects the current state of knowledge of these important
products and to develop a comprehensive and feasible clinical study
program to complement our existing pharmacovigilance program," said
Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research
and Development at Amgen. "In the current label revisions, we have
endeavored to include as much information as possible so physicians
and their patients can make informed treatment decisions."
The Company plans to hold a conference call with the investment
community at 7:00 a.m. Pacific Time on Thursday, Nov. 8, 2007, to
discuss these latest developments.
ESA Label Update
The modifications to the package insert reflect ongoing
interactions with the FDA regarding the safety and benefit/risk
profile of ESAs. These changes recognize input from the ODAC meeting
held on May 10, 2007, and the joint Cardiovascular-Renal Drug Advisory
Committee (CRDAC)/Drug Safety & Risk Management Advisory Committee
(DSaRMAC) meeting held on Sept. 11, 2007.
The revised boxed warning provides disease specific guidance for
chronic renal failure, cancer, and perisurgery indications, including
the following modifications:
- The boxed warning has additional language specific to renal
failure that states: "Patients experienced greater risks for
death and serious cardiovascular 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 has been updated
to describe studies in patients with advanced breast, head and
neck, lymphoid and non-small cell lung malignancies. These
studies administered ESAs to target a hemoglobin level greater
than or equal to 12 g/dL and were associated with shortened
overall survival and/or time to tumor progression. The warning
specifically states: "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." Physicians are further advised
to use ESAs only if patients are receiving concomitant
myelosuppressive chemotherapy and to discontinue ESA treatment
following the completion of a chemotherapy course.
- The boxed warning for the perisurgery indication has
additional language specific to perisurgery patients stating:
"EPOGEN increased the rate of deep venous thromboses in
patients not receiving prophylactic anticoagulation. Consider
deep venous thrombosis prophylaxis." (Note perisurgery
language appears only in the EPOGEN prescribing information as
Aranesp is not approved for this indication).
The WARNINGS, Increased Mortality, Serious Cardiovascular and
Thromboembolic Events were modified to include "Patients with chronic
renal failure and an insufficient hemoglobin response to ESA therapy
may be at even greater risk for cardiovascular events and mortality
than other patients." The WARNINGS, Increased Mortality and/or Tumor
Progression section was modified to include a table summarizing
studies added to the label, including the Phase 3 study in lymphoid
malignancies (161 study).
The DOSAGE AND ADMINISTRATION instructions for CRF patients were
modified to individualize dosing to achieve and maintain hemoglobin
levels between the range of 10 to 12 g/dL. For patients who do not
attain a hemoglobin level within this range despite the use of
appropriate ESA dose titration over a 12-week period, the instructions
were modified to not administer higher ESA doses and to use the lowest
dose that will maintain a hemoglobin level sufficient to avoid the
need for recurrent red blood cell transfusions. Additional
instructions include that monitoring of the hemoglobin level should be
continued and discontinuation of ESAs if responsiveness does not
improve and the patient needs recurrent red blood cell transfusions.
DOSAGE AND ADMINISTRATION instructions for cancer patients were
modified to reinforce that ESA therapy should be discontinued
following the completion of a chemotherapy course. The labeling
continues to recommend that the dose should be adjusted for each
patient to achieve and maintain the lowest hemoglobin level sufficient
to avoid the need for red blood cell transfusion and not to exceed the
upper safety limit of 12 g/dL.
The patient populations covered in the indications have not
changed. However, the revised labeling reiterates that ESAs are not
indicated for use in patients receiving hormonal agents, therapeutic
biologic products, or radiotherapy unless receiving concomitant
myelosuppressive chemotherapy. For the Aranesp product labeling the
oncology indication now states that in controlled clinical trials, ESA
use has not been demonstrated to improve symptoms of anemia, quality
of life, fatigue, or patient well-being. The updated EPOGEN product
labeling no longer contains patient-reported outcomes from older
clinical studies that did not meet recent criteria for inclusion in
the label based on FDA draft guidance, but does state EPOGEN use
improved exercise tolerance and patient-reported physical function in
dialysis patients.
Amgen submitted the changes announced today to the FDA under the
regulatory mechanism known as a "changes being effected" (CBE) and
these changes are effective immediately. However, discussions with the
FDA are ongoing, and Amgen intends to submit further modifications to
ESA product labeling to address other issues raised at the ODAC
meeting. The company expects these discussions will result in
additional revisions to class product labeling.
In the meantime, Amgen will advise prescribing health care
professionals of the current changes in the form of a Dear Health Care
Professional (DHCP) letter over the coming weeks. Prescribers are
encouraged to review the full prescribing information, which will be
posted on www.amgen.com, www.aranesp.com, and www.epogen.com.
Additionally, the European Medicines Agency's (EMEA) Committee for
Medicinal Products for Human Use (CHMP) recently reviewed the latest
clinical data for ESAs and announced that it will update the
prescribing information for ESAs in the European Union. The updated
labeling will stipulate a uniform target hemoglobin range for all ESAs
of 10 to 12 g/dL with a warning not to exceed 12 g/dL. Both the EMEA
and FDA revised labels continue to provide physician discretion to
treat patients based upon their clinical judgment.
Pharmacovigilance Program Updates
Additionally, Amgen has discussed six additional study concepts
with the FDA to address potential safety concerns in patients with non
small-cell lung cancer (two studies) and lymphoproliferative
malignancy (four studies). Based on the safety signals observed with
higher hemoglobin levels, a study to evaluate the effect of hemoglobin
target on the risk/benefit profile of ESAs is also planned.
The original pharmacovigilance program included both
investigator-sponsored and company-sponsored studies, and became part
of a formal post-marketing commitment with the FDA in 2006. All
studies that Amgen has responsibility for have either been completed
or are on track for completion by the commitment date.
Overall, we believe that the ongoing and planned pharmacovigilance
studies will result in a robust body of well-controlled data to
address concerns regarding survival and tumor progression in these
patient populations, including a total of three studies in breast
cancer, three studies in lung cancer (1 SCLC and 2 NSCLC), five
studies in lymphoproliferative malignancy, one study in head and neck
cancer, and one study to evaluate the effect of target hemoglobin
levels.
Investor Call at 7:00 a.m. PT
The Company plans to hold a conference call with the investment
community at 7:00 a.m. Pacific Time on Thursday, Nov. 8, 2007, to
discuss these latest developments.
Live audio of the conference call will be simultaneously broadcast
over the Internet and will be available to members of the news media,
investors and the general public.
The webcast of the conference, as with other selected
presentations regarding developments in Amgen's business given by
management at certain investor and medical conferences, can be found
on Amgen's Web site, www.amgen.com, under Investors. Information
regarding presentation times, webcast availability, and webcast links
are noted on Amgen's Investor Relations Events Calendar. The webcast
will be archived and available for replay 72 hours after the event.
About Aranesp
Aranesp was approved by the U.S. Food and Drug Administration
(FDA) in September 2001 for the treatment of anemia associated with
CRF for patients on dialysis and patients not on dialysis. In July
2002, the FDA approved weekly dosing of Aranesp for the treatment of
anemia caused by concomitantly administered chemotherapy in patients
with nonmyeloid malignancies and in March 2006, the FDA approved
every-three-week dosing in these patients.
About EPOGEN
Amgen launched EPOGEN, one of the first biologically derived human
therapeutics, into the U.S. medical marketplace in 1989 for the
treatment of anemia in patients with chronic renal failure on
dialysis. EPOGEN is a recombinant protein with the same mechanism of
action as endogenous human erythropoietin, a protein produced by the
kidneys to stimulate the production of oxygen-transporting red blood
cells.
Important Aranesp and EPOGEN Safety Information
WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and
THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION
Renal failure: Patients experienced greater risks for death and
serious cardiovascular events when administered erythropoiesis-
stimulating agents (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.
Cancer:
- ESAs shortened overall survival and/or time-to-tumor progression in
clinical studies in patients with advanced breast, head and neck,
lymphoid, and non-small cell lung malignancies when dosed to target a
hemoglobin of greater than or equal to 12 g/dL.
-The risks of shortened survival and tumor progression 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.
-Use only for treatment of anemia due to concomitant
myelosuppressive chemotherapy.
- Discontinue following the completion of a chemotherapy course.
Perisurgery: EPOGEN(R) increased the rate of deep venous thromboses in
patients not receiving prophylactic anticoagulation. Consider deep
venous thrombosis prophylaxis.
Aranesp and EPOGEN are contraindicated in patients with
uncontrolled hypertension.
About Amgen
Amgen discovers, develops and delivers innovative human
therapeutics. A biotechnology pioneer since 1980, Amgen was one of the
first companies to realize the new science's promise by bringing safe
and effective medicines from lab, to manufacturing plant, to patient.
Amgen therapeutics have changed the practice of medicine, helping
millions of people around the world in the fight against cancer,
kidney disease, rheumatoid arthritis and other serious illnesses. With
a deep and broad pipeline of potential new medicines, Amgen remains
committed to advancing science to dramatically improve people's lives.
To learn more about our pioneering science and our vital medicines,
visit www.amgen.com.
Forward-Looking Statements
This news release contains forward-looking statements that involve
significant risks and uncertainties, including those discussed below
and others that can be found in our Form 10-K for the year ended Dec.
31, 2006, and in our periodic reports on Form 10-Q and Form 8-K. Amgen
is providing this information as of the date of this news release and
does not undertake any obligation to update any forward-looking
statements contained in this document as a result of new information,
future events or otherwise.
No forward-looking statement can be guaranteed and actual results
may differ materially from those we project. The Company's results may
be affected by our ability to successfully market both new and
existing products domestically and internationally, clinical and
regulatory developments (domestic or foreign) involving current and
future products, sales growth of recently launched products,
competition from other products (domestic or foreign), difficulties or
delays in manufacturing our products. In addition, sales of our
products are affected by reimbursement policies imposed by third-party
payors, including governments, private insurance plans and managed
care providers and may be affected by regulatory, clinical and
guideline developments and domestic and international trends toward
managed care and health care cost containment as well as U.S.
legislation affecting pharmaceutical pricing and reimbursement.
Government and others' regulations and reimbursement policies may
affect the development, usage and pricing of our products.
Furthermore, our research, testing, pricing, marketing and other
operations are subject to extensive regulation by domestic and foreign
government regulatory authorities. We or others could identify safety,
side effects or manufacturing problems with our products after they
are on the market. Our business may be impacted by government
investigations, litigation and products liability claims. Further,
while we routinely obtain patents for our products and technology, the
protection offered by our patents and patent applications may be
challenged, invalidated or circumvented by our competitors. We depend
on third parties for a significant portion of our manufacturing
capacity for the supply of certain of our current and future products
and limits on supply may constrain sales of certain of our current
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well as for the discovery and development of new products. Discovery
or identification of new product candidates cannot be guaranteed and
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be no guarantee that any particular product candidate will be
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CONTACT: Amgen, Thousand Oaks
Dan Whelan, (805) 447-5995 (U.S. media, Nephrology)
Ashleigh Koss, (805) 313-6151 (U.S. media, Oncology)
Arvind Sood, (805) 447-1060 (investors)
SOURCE: Amgen