Is Aranesp More harmful than Helpful Now????

[RandyW]

Studies Show Anemia Drugs May Harm Cancer Patients

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By ANDREW POLLACK

Published: February 27, 2007

New studies are raising questions about whether drugs that have been used by millions of cancer patients might actually be harming them.

The drugs, sold by Amgen, Roche and Johnson & Johnson, are used to treat anemia caused by chemotherapy and meant to reduce the need for blood transfusions and give patients more energy. But the new results suggest that the drugs may make the cancer itself worse.

In the studies, the drugs have generally been used in ways not approved on the labels. And the companies say that, when used according to instructions, the drugs have a long history of safety.

In a statement yesterday, Amgen said it strongly believed its drugs were “safe and effective medicines when used in approved populations consistent with label dosing recommendations.”

Nevertheless, some cancer specialists and securities analysts say the new information may make doctors more cautious in using the drugs, which have combined sales for the three companies exceeding $11 billion and have been heavily promoted through efforts that include television commercials.

“These are drugs that were presumed to be entirely safe, given for supportive care and to improve quality of life,” not to actually treat cancer, said Dr. Eric Winer, director of breast oncology center at the Dana-Farber Cancer Institute in Boston. “So any concern that they could shorten someone’s life are taken quite seriously.”

The Food and Drug Administration is planning to convene an advisory committee meeting to review the products, Dr. Richard Pazdur, the agency’s director for cancer drugs, said in an e-mail message last week alerting cancer doctors to the new findings.

All the drugs are versions of erythropoietin, or Epo, a substance made by the human kidney that increases levels of hemoglobin, the oxygen-carrying component of red blood cells.

Amgen makes Aranesp, with sales of $4.1 billion last year, as well as Epogen, which had sales of $2.5 billion, although Epogen is supposed to be used only to treat anemia in kidney dialysis patients.

Under license from Amgen, Johnson & Johnson sells Procrit in the United States and Eprex abroad, with combined sales last year of $3.2 billion.

Roche’s drugs NeoRecormon and Epogin, now sold only outside the United States, had sales last year of $1.8 billion. But Roche is hoping to enter the American market with a new drug called Cera.

Amgen has the most to lose from any setback because it relies more heavily on the Epo drugs, which account for nearly half its revenue. Amgen’s stock touched above $75 briefly in late January, before word of the negative studies began emerging. The shares closed yesterday at $66.20, down 3 cents.

The new doubts about cancer safety add to those raised recently regarding the drugs’ other major use — to treat anemia caused by kidney disease. A study published in The New England Journal of Medicine in November found that patients treated aggressively with Procrit had a higher risk of heart problems or death than those treated less aggressively.

The run of bad news for cancer treatment started in late January when Amgen announced that in one of its clinical trials, patients getting Aranesp were more likely to die than those getting placebo. The trial was testing the drug in patients whose anemia was caused by the cancer itself, not by chemotherapy.

On Feb. 16, the Cancer Letter, an influential Washington newsletter, reported that a Danish study in patients with head and neck cancer had been stopped early because the cancer seemed to recur more in patients being treated with Aranesp.

Last week, The Journal of Clinical Oncology published a paper online describing a small Canadian trial in lung cancer patients that had been stopped early because those getting Eprex were dying sooner.

And on Friday, Roche said it was suspending patient enrollment in a lung cancer trial comparing its Cera against Amgen’s Aranesp because of apparently greater than expected number of deaths in at least some of the arms of the trial.

It is not known why the drugs cause problems, if they do. It is known that raising hemoglobin levels too high increases the risk of blood clots. And most of these new trials did aim to increase hemoglobin above the levels recommended in the drugs’ labels, though that was not the case with Amgen’s own trial.

But there is some evidence that clots were not the problem in these trials. Rather, some experts say, Epo may spur tumor growth. Some studies suggest that certain tumor cells, such as those in head and neck cancer, have proteins on their surface that bind to Epo. When that happens it sets off a cascade of reactions spurring growth.

“I think there’s enough biologic plausibility to the argument that they can serve as a growth factor for the cancer cell,” said Dr. Jennifer R. Grandis, a professor at the University of Pittsburgh who has done studies of the matter. She said the head and neck cancer practice at her institution does not routinely use Epo and that she would not want it herself.

But Dr. David P. Steensma at the Mayo Clinic, who has reviewed studies of Epo safety, said the existence of Epo receptors on tumors had not been proved because the studies have been flawed. He said that there have been previous studies of the drugs that suggested they actually had a positive effect on survival.

A combined analysis of 57 trials concluded the impact of the drugs on survival was uncertain.

Dr. Steensma said he was still comfortable using the drugs to correct severe anemia, but added, “I think we need to be real careful about going beyond that.”

Concerns about the safety of the drugs for cancer were first raised in 2003 by two studies that showed patients getting Epo had worse outcomes. But some experts said those studies were flawed and not convincing.