Aranesp(R) Phase 3 Study in Patients with Active Cancer Not Receiving Concurrent Chemotherapy or Radiotherapy Presented at AACR Annual Meeting
THOUSAND OAKS, Calif.--(BUSINESS WIRE)--April 16, 2007--Amgen
(Nasdaq:AMGN) today presented the results from a randomized,
double-blind, placebo-controlled Phase 3 study evaluating the efficacy
and safety of Aranesp(R) (darbepoetin alfa) for the treatment of
anemia in patients with active cancer not receiving chemotherapy or
radiotherapy ("the 103 study"). Aranesp is not approved for use by the
FDA or EMEA in these patients. These results were presented in an oral
session at the 2007 American Association for Cancer Research (AACR)
annual meeting in Los Angeles, Calif. (AACR Abstract #LB-3).
As reported in January, the study did not meet its primary
endpoint of reducing red blood cell (RBC) transfusions in the Aranesp
treatment group. Transfusion occurrences from weeks 5 to 17 favored
Aranesp but were not statistically significant between the groups
(hazard ratio: 0.85, p=0.32). Among those receiving Aranesp, there was
a significantly higher proportion of patients with a hemoglobin
response (p less than 0.0001), hemoglobin correction (p less than
0.001), and hematopoietic response (p=0.002) compared with placebo.
The adverse event rate was similar between the groups. However,
the overall number of deaths was greater in the Aranesp group (48.5
percent versus 46 percent in placebo; hazard ratio: 1.29; p=0.006). In
post-hoc analyses adjusting for stratification factors at
randomization and sex, stage IV disease, prior chemotherapy use and
prior radiotherapy use, there remained a significant difference in
survival between the groups. However, hazard ratios and statistical
significance diminished when the analyses were further adjusted for
known prognostic factors including baseline ECOG status, tumor type,
tumor stage, baseline FACT-F cutoff at median and baseline Hb (hazard
ratio: 1.17, p=0.11).
"This study evaluated ESA treatment for patients with active
cancer, not receiving chemotherapy or radiation, who are anemic due to
the cancer itself. Unfortunately, the benefit of ESA treatment was not
observed in these gravely ill patients," said John Glaspy, M.D.,
professor, David Geffen School of Medicine, University of California
at Los Angeles. "Since this was not designed as a survival study and
statistical significance diminished when the analyses were adjusted
for known prognostic factors, there is no clear explanation for the
increase of deaths in the Aranesp group."
About the Study
This Phase 3 study was designed to evaluate the efficacy and
safety of Aranesp 6.75 mcg/kg administered every four weeks for the
treatment of anemia in cancer patients not receiving chemotherapy or
radiotherapy. The study was conducted in 21 countries, including sites
in Western Europe, Central and Eastern Europe, Australia and North
America. The majority of patients (60 percent) were from Central and
Eastern Europe.
Patient eligibility included: greater than or equal to 18 years,
nonmyeloid malignancy (with active disease), hemoglobin (Hb) less than
or equal to 11 g/dL, and no chemotherapy or radiotherapy treatment
within four weeks of screening or during the study. Patients (n=985)
were randomized to Aranesp 6.75 mcg/kg or placebo every four weeks,
with an end of study visit at week 19, and two years of follow up to
evaluate survival. Patients were stratified by screening Hb (less than
10 g/dL or greater than or equal to 10 g/dL), geographic region
(Europe versus rest of world), RBC transfusion in the prior 12 weeks,
tumor type/treatment (specifically, diagnoses of chronic lymphocyctic
leukemia or low grade lymphoma, ongoing hormonal or antibody therapy
versus all other eligible patients), and ECOG status (0-1, 2).
Demographics were broadly similar between the groups. The mean
(SD) age was 64.1 (11.6) years; the most common cancers were non-small
cell lung (18 percent), breast (13 percent), and prostate (11
percent); most patients had disease stage III or IV (82 percent) and
an ECOG status of 0 or 1 (72 percent); and baseline Hb was 9.5 g/dL in
each group.
However, there were more men in the Aranesp group (56 percent)
compared to the placebo group (47 percent) and overall survival was
worse for men than women (hazard ratio: 1.38 versus 0.99,
respectively). More patients received prior chemotherapy in the
Aranesp group (73 percent versus 66 percent in placebo). The mean (SD)
number of days between prior chemotherapy and first study drug dose
was 262 (572) days for the Aranesp group compared to 315 (660) for the
placebo arm.
About Aranesp
Aranesp was approved by the U.S. Food and Drug Administration
(FDA) in September 2001 for the treatment of anemia associated with
chronic renal failure (CRF), also known as chronic kidney disease
(CKD), for patients on dialysis and patients not on dialysis. In July
2002, the FDA approved weekly dosing of Aranesp for the treatment of
chemotherapy-induced anemia in patients with nonmyeloid malignancies
and in March 2006, the FDA approved every-three-week dosing in these
patients.
Important Safety Information
Use the lowest dose of Aranesp that will gradually increase the
hemoglobin concentration to the lowest level sufficient to avoid the
need for red blood cell transfusion (see DOSAGE and ADMINISTRATION in
the prescribing information).
Aranesp and other erythropoiesis-stimulating agents (ESAs)
increased the risk for death and for serious cardiovascular events
when administered to target a hemoglobin of greater than 12 g/dL (see
WARNINGS: Increased Mortality, Serious Cardiovascular and
Thromboembolic Events).
Cancer Patients: Use of ESAs
-- shortened the time to tumor progression in patients with
advanced head and neck cancer receiving radiation therapy when
administered to target a hemoglobin of greater than 12 g/dL;
-- shortened overall survival and increased deaths attributed to
disease progression at 4 months in patients with metastatic
breast cancer receiving chemotherapy when administered to
target a hemoglobin of greater than 12 g/dL;
-- increased the risk of death when administered to target a
hemoglobin of 12 g/dL in patients with active malignant
disease receiving neither chemotherapy nor radiation therapy.
ESAs are not indicated for this population.
(See WARNINGS: Increased Mortality and/or Tumor Progression in the
prescribing information).
The Aranesp prescribing information, including important safety
information and boxed warning, may be accessed at www.aranesp.com.
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Aranesp prescribing information can be accessed by calling
800-772-6436 or by logging on to www.aranesp.com.
CONTACT: Amgen, Thousand Oaks
Ashleigh Koss, 805-313-6151 (media)
Arvind Sood, 805-447-1060 (investors)
SOURCE: Amgen