Puzzling risks of Aranesp and other red cell boosters

[Tom]

Greater caution on anemia drugs seen after deaths

Ransdell Pierson and Bill Berkrot
Reuters Health
Posting Date: January 29, 2007

Last Updated: 2007-01-29 15:30:33 -0400 (Reuters Health)

NEW YORK (Reuters) - The higher mortality risk revealed in a trial of Amgen Inc.'s Aranesp and similar anemia medicines underscores the need to restrict their use and better understand how they work, analysts and drugmakers say.

"There will be less of a knee-jerk reaction to prescribe them," Dr. Stephen Malamud, an oncologist with Beth Israel Hospital in New York said on Friday. "This will give doctors a reason to pause and think that maybe it's not best to put everyone on the drug."

Amgen shares closed 4.5% lower on Friday after the drugmaker described a trial in which a significantly higher risk of death was seen among advanced cancer patients taking Aranesp who were not undergoing chemotherapy or radiation, than those taking a placebo.

Roger Perlmutter, Amgen's executive vice president for research and development, said the patients in the cancer anemia trial had "an especially grave prognosis."

"There's no question that any time you go into a patient population that's more seriously ill, you run the risk of getting an adverse result," he said.

Like Johnson & Johnson's rival drugs Eprex and Procrit, and Amgen's older Epogen, Aranesp's active ingredient is erythropoietin (EPO).

Aranesp, a $4 billion-a-year drug that is Amgen's biggest product, is approved to treat anemia caused by chemotherapy and for kidney disease patients.

"We have great confidence in our labeled indications for which there's an enormous amount of data supporting favorable benefit/risk profile, if used according to the label," Perlmutter said.

Still, there seem to be mounting doubts about the safety of this class of drugs.

The Aranesp setback came only months after a study showed that kidney disease patients given high doses of Procrit ran a higher risk of cardiac complications and death than patients treated less aggressively.

Similarly, a European study of Eprex several years ago showed patients with advanced breast cancer whose red blood cell levels were pushed to very high levels by aggressive treatment also had greater risk of death.

J&J spokesman Mark Wolfe said on Friday the labels on all EPO drugs have been changed since then to reflect the dangers of using overly high doses.

"We are confident that Procrit is safe and effective when used within the target hemoglobin levels specified in the product label," he said.

Malamud said the lion's share of cancer patients receiving EPO drugs are the population for which they are intended -- those undergoing chemotherapy or radiation.

Amgen speculated that 10% to 12% of Aranesp sales were "off-label", for patients not undergoing chemo or radiation treatments.

"These drugs are an incredibly important part of treatment for cancer patients," Malamud said, but added that their safety is not fully understood.

In previous years, he said drugmakers and U.S. regulators were overwhelmingly focused on how well they raised levels of red blood cells and reduced the need for blood transfusions -- giving short shrift to how they might affect the rest of the body.

Many people assume the higher deaths in some trials were caused by blood clots, he said. "But it may be that the drug is interacting with the tumor and causing it to grow," Malamud added.

He said drugmakers should more diligently assess what effects, if any, the drugs have on tumor control and survival.

"We have lots of ongoing studies that will, I think, illuminate the broader landscape of how best to use Aranesp and in which patient populations," Perlmutter said. He said there was no persuasive evidence indicating EPO drugs help tumors grow.

[Becky]

While on chemo, my red cell count dropped but never enough for a Procrit shot. I was glad because there is a warning on the Procrit label that states that cancer survival is less if you use Procrit. I did alot of research into it then and it seemed that Procrit (or drugs like it) cause an increase in mortality. Sometimes I would think that it was because those patients using it were in the worst shape (medically) and therefore at a higher increase in the rate of death. Secondly, I had read another article that said that even if you are on the edge of needing red blood cell boosting, take it. This article's thought was that cancer survives and reproduces better in a low oxygen state. Therefore, if the red blood cells are at normal or boosted levels, there will be more oxygen in the body. Makes sense in that regard but overwhelmingly, the Procrit label is scary.


This comes on the heels of your last post on Neulasta/Nepogen which I have always agreed with. I did not take Neulasta but took Leukine instead. My rationale was that Leukine boosts all white blood cell components (including the dendrites which are the scouts of the immune response system - thereby a potential self vaccinating system). Whereas the Neulasta just boosts neutrophils (which is all the oncs really care about) and is a one shot deal so they don't have to see you for 2 weeks (Leukine you need a shot every 24 hours for 10 days - no "lasta" effect).

Thanks for posting this one Tom as it rounds out the red and white blood cell count issues and gives us all something more to think about and ponder.