Amgen details higher death risk in Aranesp trial

Amgen Inc. said on Monday that 48.5 percent of cancer patients not undergoing chemotherapy or radiation who received its anemia drug Aranesp in a clinical trial died compared with 46 percent of patients on placebo as the company released details of a previously reported study.

Amgen, which had disclosed the higher Aranesp death rate in January, released full data from the trial at a meeting of the American Association for Cancer Research.

The Thousand Oaks, California-based company had also reported in January that the study did not meet its main goal of showing Aranesp could reduce the need for blood transfusions in those patients. At the time it did not give specific numbers.
Amgen said the results suggest that the risk of taking Aranesp is not justified for patients with unexplained anemia and active cancer -- those who are not in remission and not receiving chemotherapy -- and it would no longer seek approval for the condition known as anemia of cancer.

Dr. John Glaspy, one of the study's researchers, said there is no clear explanation for the higher death rate in the Aranesp group, but said mechanisms could include that the drug provides oxygen to tumors, increases blood clots or even attaches to receptors on cancer cells.

Some doctors have expressed concern that anemia drugs like Aranesp, which are forms of the red blood cell-boosting protein erythropoietin, may actually feed the growth of tumors.

Aranesp, a longer-lasting version of Amgen's older anemia drug Epogen, is approved for use in patients with chronic kidney disease and for cancer patients whose anemia is caused by chemotherapy. It is Amgen's top seller, with sales last year of $4.1 billion.

"We have to conclude that these agents may reduce survival in patients who are not receiving chemo and we should restrict the use in these patients," said Glaspy, a professor at the University of California, Los Angeles.

The U.S.Food and Drug Administration last month required a strong new warning on the label of Aranesp and similar anemia drugs calling on doctors to use the lowest dose that can effectively avoid the need for blood transfusions.

While chemotherapy-induced anemia is Aranesp's primary use, Amgen said off-label use in anemia of cancer accounted for about $560 million of Aranesp global sales last year.

The Phase III study involved 985 patients, mostly from Central and Eastern Europe, who were treated with Aranesp, which is given by infusion, or a placebo.

Patients were treated for 16 weeks and followed for two years. During the study, Aranesp was withheld if the patient's hemoglobin count exceeded 13 grams per deciliter.

Amgen said that after taking into account factors such as the patient's degree of illness and tumor type, the statistical significance in the death rate diminished.

"Some tumor types are more aggressive than others," said Roy Baynes, vice president of clinical development at Amgen.

The researchers noted that Aranesp patients with kidney, prostrate, or stomach cancers, non-Hodgkin's lymphoma or multiple myeloma appeared to have worse survival outcomes, but the opposite was seen for patients with breast, colon, ovarian, or cervical cancer.

Baynes noted that regulators required Amgen to bar from the trial patients whose cancer had gone into remission, but earlier-stage trials had included those patients.

The company's share price has tumbled about 20 percent since mid-January after a number of setbacks, including preliminary results from this Aranesp trial.

Amgen is expected to announce next Monday results from a study of Aranesp's effect on death rates among patients with small-cell lung cancer who are undergoing chemotherapy.

Dr. David Steensma, a hematologist at the Mayo Clinic in Rochester, Minnesota said doctors have become more cautious about prescribing biologic anemia drugs, possibly targeting lower hemoglobin levels than previously, as they await further clinical trial data and results of an FDA advisory committee meeting scheduled for May 10.

Amgen's stock closed up 62 cents at $59.65 on Monday.