ESA Restrictions Leave Many Questions Unanswered

Mar 19, 2008
By Pharmaceutical Executive Editors

The Oncologic Drugs Advisory Committee (ODAC) of the FDA last week recommended updated restrictions for erythropoiesis-stimulating agents (ESAs), such as Aranesp and Epogen, when used to treat chemotherapy-induced anemia. The drugs are traditionally used to prevent the need for blood transfusions during chemotherapy, but have recently been shown to expand all cancers and have the increased possibility of causing a blood clot.

Although ODAC's recommendations are being seen as a step in the right direction, some patient advocacy groups feel that the committee failed to create a plan to determine if the drugs in question are truly dangerous and at what level they become dangerous.

"ODAC's ruling did not pave a path to get that type of information," said Andy Giusti, Colorectal Cancer Coalition (C3) board member–elect. "They went ahead and recommended that FDA restrict the use of ESAs in particular cancer types and recommended an informed-consent process for use by everybody, but they didn't put anything forward that would help determine unequivocally whether or not the drugs are safe to be used per their label indication."

Who Benefits? Who Is Harmed?
The committee's recommendations were:

  • ESAs should remain available to cancer patients.
  • They should not be used in breast or head and neck cancer, conditions in which research suggests the drugs might shorten life expectancy.
  • ESAs should also be used only in advanced stages of cancer, rather than as part of a course of treatment intended to cure the disease.
  • Patients should be required to sign a consent form prior to starting treatment to make them fully aware of the adverse effects of the drug.

"The 13-to-1 vote to leave the oncology indication intact was the right choice; the rest of the recommendations are harder to interpret," said Robert Erwin, president of Marti Nelson Cancer Foundation, a patient advocacy group. "Once you vote that the drugs do provide benefit to some cancer patients, it then becomes a question of how do you best define who is likely to benefit and who is likely to be harmed?"

The committee looked at data from studies related to head, neck, and breast cancers that showed potential safety issues, including a tumor-promoting effect. C3 argued that in order to make a proper recommendation, ODAC should have looked at a wider range of data.

"The reason there was so much discussion of certain cancers was because that's where there was data," Erwin said in an interview with Pharm Exec. "There is no solid evidence to show that there is more risk in one cancer area than others. That absence of information makes it frustrating when you have to figure out what information to put on a label."

Beyond Restrictions
C3 recommended the establishment of a patient registry or a special restricted-distribution program. It would require patients to give the informed consent, but then data would be collected as to how the patient responded to treatment.

"This isn't just about making sure that the patient understands the risks involved, but that then there's information being collected on the person and the person's health and at what level they receive the drug," C3 President Carlea Bauman told Pharm Exec.

The drug companies recommended a Phase III trial that in eight years would accrue enough patients to allow FDA to make an informed decision. Many feel that the trial would have a tough time getting patients.

"Although these safety signals have been inconsistently observed across a number of ESA studies, Amgen nonetheless takes them very seriously and is committed to conducting a controlled clinical trial based on the current label to definitively address these issues," Roger M. Perlmutter, executive vice president, of research and development at Amgen, stated in a release.

The recommendations will now go before FDA, which has the daunting task of sifting through all the commentary and data and deciding on proper labeling rules.

"I think ODAC is moving in the right direction," Erwin said. "It's a very complicated issue, and people who expected a quick, simple conclusion were maybe expecting too much too fast. This is not something as simple as banning a toxic drug or ignoring safety signals."

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