ESAs can be given to chemotherapy patients to reduce the need for blood transfusions.  However, there can be problems with ESAs including causing some tumors to grow faster or some patients to die sooner.  They can also increase risk for blood clots, heart failure, heart attack or stroke.

ESAs, including Procrit®, Epogen®, and Aranesp®, are now covered by a REMS or Risk Evaluation and Mitigation Strategy which requires that patient receive a Medication Guide from their health care providers that tells them how to safely use an ESA drug.

In addition, health care providers who use ESAs with their patients must be be actively enrolled in  the APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe Use of ESAs) Oncology program and receive training in their safe use. 

ESAs are forms of the human protein erythropoietin, which stimulates bone marrow to make red blood cells.   Chemotherapy can cause anemia, which is the loss of these cells.  If red cells counts fall too low, a blood transfusion may be necessary.

Because of the potential risks of ESA treatment, the FDA required Amgen, Inc., which manufacture Aranesp, Epogen, and Procrit, to develop a Medication Guide and REMS.

The Medication Guide tells patients:

• If you decide to take an ESA, your healthcare provider should prescribe the smallest dose to lower the chance of getting red blood cell transfusions.
• After you have finished your chemotherapy course, ESA treatment should be stopped.
• ESAs do not improve the symptoms of anemia (lower than normal number of red blood cells), quality of life, fatigue, or well-being for patients with cancer.
• You may get serious heart problems such as heart attack, stroke, heart failure, and may die sooner if you are treated with an ESA to a hemoglobin level above 12 g/dL.
• You may get blood clots at any time while taking an ESA . If you are receiving ESA and you are going to have surgery, talk to your healthcare provider about whether or not you need to take a blood thinner to lessen the chance of blood clots during or following surgery. Clots can form in blood vessels (veins), especially in your leg (deep venous thrombosis or DVT). Pieces of a blood clot may travel to the lungs and block the blood circulation in the lungs (pulmonary embolus).
• Before ESA treatment begins, patients must sign an acknowledgment form that says they have talked with their healthcare professional about the risks of ESAs.

The APPRISE Oncology program requires that health care professionals who treat cancer patients with ESAs:

• Complete a training module that covers the use of ESAs. Completion of the training module is required for enrollment in the ESA APPRISE Oncology program.
• Sign the patient/healthcare professional acknowledgement form prior to the patient receiving an ESA. The acknowledgement form attests that the healthcare professional and patient have discussed the risks of using an ESA.
• Re-enroll in the ESA APPRISE Oncology program every three years.

Only health care professionals who are part of APPRISE can prescribe ESAs for their cancer patients receiving chemotherapy.

Richard Pazdur, M.D., director of the Office of Oncology Products in the FDA’s Center for Drug Evaluation and Research said,

Evaluation of Erythropoiesis-Stimulating Agents has been an ongoing and intensive process since 2004, involving a series of public meetings, labeling changes, and a required Medication Guide. This new risk management program will help ensure that patients and their health care professionals have fully considered the benefits and risks of using ESAs.

Disclosure: C3 has accepted funding for projects and educational programs from Amgen in the form of unrestricted educational grants. C3 has ultimate authority over website content.

Dingell in a statement said, “Marketing department leaders have failed to commit to reducing misleading and deceptive ads, so we’re now asking the CEOs to make this agreement.” Stupak said, “We intend to make certain that drug companies market their product properly in order to protect American consumers from manipulative commercials designed to mislead and deceive for profit.”

The letters relate to a May 8 hearing in which representatives from the four pharmaceutical companies defended their DTC advertising. The hearing focused on three broadcast ads: Pfizer’s ads for Lipitor featuring Dr. Robert Jarvik, Merck/Schering-Plough’s “Food & Family” ads for Vytorin and Johnson & Johnson’s ads for Procrit.

The letters ask for an “immediate” response, while a second hearing on DTC advertising is being considered.

Click here to read the Energy and Commerce Press Release.

Background:

All of us have seen drug advertisements on TV, where benefits and risks of drugs are laid out. This type of advertising (Direct to Consumer, or DTC) is required to advertise only the benefits approved by the Food and Drug Administration (FDA), and must also include known risks of the drug.

Epogen, the original form of Procrit, was approved by the FDA in 1993 as a way to minimize the need for blood transfusions due to anemia caused by chemotherapy treatment. Ortho Biotech, the company which sells Procrit, did not complete FDA-approved research to prove that Procrit reduces fatigue and improves the quality of life for cancer patients.

However, DTC which implied that Procrit would improve a cancer patient’s quality of life by relieving fatigue ran from 1998 to 2005. Since Procrit was approved to help patients avoid transfusions, not to deal with fatigue, C3 believes that promoting Procrit for cancer fatigue was misleading.

In 2007, C3 filed a Freedom of Information (FOI) request with the FDA, and asked why these advertisements were allowed to run. The FDA’s response did not explain to C3’s satisfaction why these advertisements were allowed. Thus, C3 was very pleased when the House panel convened a hearing on DTC advertisements.

The Hearing:

Members of the Committee solicited testimony from experts in patient communication, and from senior executives from Ortho Biotech, Pfizer and Merck/Schering Plough.

Testimony explored issues such as:
• Does DTC advertising influence the American public’s treatment choices in a supportive or detrimental way?
• Is current advertising done ethically, with full and appropriate disclosure risks and benefits?

“Congress should consider whether ads promoting medicines should be allowed to continue to target consumers in the United States,” said Congressman Bart Stupak. “We should make sure that pharmaceuticals companies conduct themselves responsibly.”

Ruth Day, head of Duke University’s Medical Cognition Laboratory, told lawmakers that “drug companies use a variety of tactics to highlight a drug’s benefits and downplay risks, including fast speech to visual effects.” She referred to TV commercials where the benefits are personally explained by a physician, while risks are explained by an anonymous voice speaking very rapidly.

The Government Accountability Office (GAO) criticized the FDA for not acting in a timely fashion when they suspected companies of violating DTC rules. Marcia G. Crosse, Director, Health Care, U.S. Government Accountability Office, referenced a report the GAO did in 2006 during her testimony, “By the time the agency issued regulatory letters, drug companies had already discontinued use of more than half of the violative advertising materials identified in each letter. In addition, FDA’s issuance of regulatory letters had not always prevented drug companies from later disseminating similar violative materials for the same drugs.”

The drug company executives consistently claimed that their advertisements were truthful and in line with FDA guidelines. When it came to Procrit, Stupak said, “This was clearly an instance of off-label marketing practice that is prohibited by FDA.” Ortho Biotech President Kim Taylor said, “Statements in the advertisements regarding the benefits of Procrit were true, responsible and substantiated by scientific studies.” (Newark Star-Ledger, 5/9)

Oddly, the FDA was not part of the hearing. The FDA is the agency that oversees these ads and decides whether they are appropriate for American consumers. One fundamental question asked but not answered is whether the FDA doing their job effectively.

Ranking Member John Shimkus of Illinois said since new legislation recently gave FDA additional power to regulate DTC advertising, it was too soon for lawmakers to intervene, “We gave the FDA power to act and we haven’t really given them time to really impose civil fines on false and misleading ads.”

Stupak disagreed. “The FDA is toothless,” declared Stupak. “Congress needs to decide whether the US should continue being one of only two countries in the world that allows direct-to-consumer ads, and if we continue to allow such advertising, whether any further limits on direct-to-consumer ads should be required.” New Zealand is the only other country that allows DTC advertising. (FDAnews, 5/12).

The end of the hearing did not bring closure to the DTC question. The democrats on the Committee concluded that an additional hearing that included the executive leadership of the companies was necessary; however, a date was not set. Congressman Stupak stated, “I think the issues in this hearing are more related to overall drug company clinical and claims behavior than DTC specifically. I do not expect any actions to come from the hearing that would affect DTC.”

C3 has led the patient advocate community on this issue by prodding the FDA and companies for answers. In addition, C3 worked with the Oversight Subcommittee on questions to be asked of Kim Taylor, President of Ortho Biotech.

The hearing and its material can be viewed online.