In
March 2007 and again this past November, the U.S. Food and Drug Administration
(FDA) approved “black
box” warnings and other safety-related product label changes for erythropoiesis-stimulating
agents (ESAs). These drugs -- the most
common of which is erythropoietin (EPO;
brand names Procrit, Epogen) -- stimulate red blood cell production and are used
to treat anemia.
 |
erythropoiesis-stimulating
agents (ESAs) |
 |
|
Red
Blood Cells |
The
action by the FDA and drug manufacturers was in response to new study data indicating
that ESAs may significantly increase the risk for serious
cardiovascular complications in people
with kidney disease.
In
addition, other studies showed that use of these agents by people with certain
types of cancer was associated with more rapid tumor growth and increased risk
of death. Cancer patients use ESAs to manage the hemotoxic side effects of chemotherapy, as do many people
with HIV and hepatitis C to counter the side effects of AZT (zidovudine;
Retrovir) and ribavirin,
respectively.
These
findings prompted the FDA to undertake a more through review of the research on
ESAs. Following is the edited text of a January 3, 2008
agency announcement about additional study data that have since become available:
FDA Receives New Data on Risks of Anemia Drugs Consistent
With Previous Data on Tumor Growth and Death
The
U.S. Food and Drug Administration (FDA) is reviewing new data from two studies
that provide further evidence of the risks of anemia drugs known as erythropoiesis-stimulating
agents, or ESAs. The studies show that patients with
breast or advanced cervical cancers who received ESAs
to treat anemia caused by chemotherapy died sooner or had more rapid tumor growth
than similar patients who didn’t receive the anemia drug.
These
two studies were not among the six studies that were described in revised labeling
approved by FDA Nov. 8, 2007, which strengthened warnings about ESAs
in cancer patients.
Taken
together, all eight studies show more rapid tumor growth or shortened survival
when patients with breast, non-small cell lung, head and neck, lymphoid, or cervical
cancers received ESAs compared
to patients who did not receive this treatment. In all of these recent studies,
ESAs were administered in an attempt to achieve a hemoglobin
level of 12 grams per deciliter (g/dL) or greater, although
many patients did not reach that level.
FDA
plans to discuss this new data and revisit the risks and benefits of using ESAs
in patients with chemotherapy-induced anemia at a public advisory committee meeting in the next few months.
“This
new information further underscores the safety concerns regarding the use of ESAs in patients with cancer, which FDA addressed in previous
communications,” said Janet Woodcock,
MD, FDA's deputy commissioner for scientific
and medical programs, chief medical officer, and acting director of the Center
for Drug Evaluation and Research.
“FDA
is reviewing these data and may take additional action. In the meantime, FDA recommends that health care providers review the risks
and benefits of ESAs outlined in the product label and
discuss this information with their patients.”
ESAs are a bioengineered version of a natural
protein made in the kidney that stimulates the bone marrow to produce more red
blood cells.
Physicians
determine whether a patient is anemic and decide on ESA dosing by measuring how
much of the protein known as hemoglobin is present in a patient's red blood cells,
typically expressed in grams per deciliter.
FDA-approved
uses of ESAs are for the treatment of anemia in patients with chronic
kidney failure; for cancer patients whose anemia is caused by chemotherapy; and
for those infected with the human immunodeficiency virus (HIV) whose anemia is
caused by the HIV drug AZT (zidovudine). ESAs
are also approved to reduce the number of transfusions during and after major
surgery.
On
Nov. 30, Amgen, manufacturer of the three ESAs – Aranesp
[darbepoetin], Epogen, and
Procrit -- provided FDA with information from the 733-patient
PREPARE study of women who received chemotherapy before undergoing surgery for
breast cancer. After three years, 14 percent of the patients who received Aranesp
to treat their anemia had died, compared to 9.8 percent who did not receive the drug.
Tumor growth was also faster in patients receiving Aranesp.
On
Dec. 4, Amgen informed FDA of the results of a study by the National Cancer Institute’s
Gynecologic Oncology Group of patients receiving chemotherapy and radiation for
advanced cervical cancer. The patients were administered either Procrit
to maintain hemoglobin levels above 12 g/dL or blood
transfusions as needed. After three years, 66 percent of the patients who did
not take Procrit were alive and free of cancer growth
compared to 58 percent who had received
the drug.
FDA
approved revised boxed warnings and other safety-related product labeling changes
for ESAs in November and March 2007. Safety concerns regarding
ESAs were discussed during advisory committee
meetings in 2004 and 2007 and labeling was revised in 1997, 2004 and 2005 to reflect
new safety information
This
communication is in keeping with FDA's
commitment to inform the public about
its ongoing safety reviews. FDA is committed to strengthening the science that supports
medical product safety at every stage of the product life cycle from pre-market
testing and development through post-market surveillance and risk management.
1/18/08
Source
U.S. Food and
Drug Administration. FDA Receives New Data on Risks of Anemia Drugs. Press release. January
3, 2008.
