May 4, 2004 -- Two popular anemia drugs are under scrutiny by an FDA advisory panel because of ongoing concern that the medications may lead to early death in some patients with cancer and other diseases.
Experts met with drug makers and FDA officials in an effort to monitor several studies involving the drug erythropoietin (EPO). The drug, which raises red blood cell counts, is popular with cancer patients who develop anemia, or low red blood cells, during chemotherapy. Many doctors favor the drugs because they can help combat the fatigue associated with anemia while avoiding the need for blood transfusions.
Meanwhile, makers of Procrit and Aranesp, two EPO drugs available in the U.S., defended their products as relatively safe and suggested that the drugs may even extend patients' lives. They pledged to move quickly on several ongoing clinical studies aimed at answering lingering safety questions.
"We have these evolving safety concerns. They cannot be dismissed," says Harvey Luksenburg, MD, a medical officer in the FDA's division of therapeutic biological oncology products.
Experts are most concerned about a handful of large European studies showing that EPO drugs may cause cardiovascular problems or even worsening cancers in patients on chemotherapy.
One study performed on 940 women on chemotherapy for breast cancer showed a 2.3% rate of fatal blood clots or other fatal cardiovascular events in women taking Eprex, an EPO drug available in Europe but not in the U.S. Women taking placebo pills had a 0.4% rate of the fatal events, nearly six times lower. The study was planned to last a year but was stopped after just four months because of the safety problems.
In another European study in 2003, cancer patients taking the EPO drug NeoRocormon had an 11% rate of dangerous cardiovascular events such as stroke, hemorrhage, or blood clots, while those on placebo had a 5% rate.
Results from that study also showed that patients on placebo were less likely to see their cancers progress, suggesting that EPO could be having a cancer-promoting effect.
Other studies showed no risk of dangerous heart problems with the drug and no signs that the drugs promote cancer. Overall FDA reviewers found four studies showing a higher risk of heart problems with EPO and three showing no increased risk.
Drug manufacturers defend their products, noting that large scale trials conducted in Europe show that EPO drugs have no impact on the overall survival rates of patients with lung cancer, lymphatic cancer, and other malignancies. While many studies have indicated an increased risk of blood clots in patients taking EPO, patients' overall life spans were not affected, says David Parkinson, MD, vice president for oncology clinical development for Amgen, Inc. The company makes the EPO drug Aranesp.
"We believe that our detailed examination confirms the safety profile of Aranesp," he says.
Parkinson referred to "a significant amount" of preliminary evidence showing that the drug could pose a measurable benefit to anemic patients on chemotherapy.
Both company and government officials agreed that more studies are needed to determine what effect EPO has on patients with different kinds of cancers, and whether or not the drug could actually have an effect directly on cancer cells, possibly causing them to grow.
American Volunteers Needed
Still, regulators and experts remain concerned that most if not all of the large EPO studies were performed in Europe and not the U.S. Officials expressed worry that American patients and their doctors may continue to shy away from signing up for trials where they could be randomized to take EPO or a placebo.
"The real question is, will they be willing to be randomly assigned," says Musa Meyer, a consumer advocate and member of the FDA's advisory panel for oncologic drugs. "I think there are physicians for whom it will be an issue."
Company officials said that several trials testing EPO drugs in patients with lung cancer, breast cancer, lymphoma, and head and neck cancers are continuing to recruit hundreds of patients. But those studies are all continuing in Europe.
"We will have those data very shortly," says Martine George, vice president for hematology and oncology research for Procrit maker Johnson and Johnson. Trials in the U.S. have largely ground to a halt because researchers have had trouble getting patients to sign up.
"We believe the findings should absolutely be applicable to United States practice," Parkinson says of the European research.