Sen. Grassley Seeks to Empower FDA to Access Drug-Risk Information From Drug Makers

SEN. GRASSLEY SEEKS TO EMPOWER FDA TO ACCESS DRUG-RISK INFORMATION FROM DRUG MAKERS

Sen. Chuck Grassley wants to make sure drug makers fully disclose data from their drug studies to the Food and Drug Administration, and he's asking the drug-safety agency if it needs new power to collect such information and a major drug maker to account for how it handled requests from the FDA for information about anti-anemia drugs given to kidney and cancer patients.

In letters sent this week, Grassley has asked the FDA to identify any new tools it might need to gain access to necessary information from drug makers. He also has asked Amgen to respond to allegations that it limited FDA access to the results of company studies and did not provide complete responses to the agency's requests for data.

"The Senate has already passed its FDA revitalization legislation, but the House of Representatives hasn't acted yet, so there's still time for congressional leaders to consider new and important measures to strengthen the hand of the FDA in looking out for American consumers," Grassley said. "There could be important lessons to learn from this particular case, and since Congress doesn't act very often on FDA legislation, so we ought to focus on what happened in a very time-sensitive way."

Amgen is the maker of erythropoisesis-stimulating agents, which are used for the treatment of anemia in patients with chronic kidney failure as well as chemotherapy-induced anemia. Last week an FDA advisory panel recommended that more information should be provided about the risks of these drugs and new studies should be conducted to assess the drugs' safety. In addition, news organizations reported assertions that Amgen had not provided study data to the FDA upon request and had not been up front about safety risks.

Last month, Grassley asked the Centers for Medicare and Medicaid Services to address reimbursement and drug safety concerns related to the use of these anti-anemia drugs. Grassley said he has received a preliminary response to this inquiry and will continue to pursue a payment policy that guards both tax dollars and patient safety.

The text of Grassley's letters to the FDA, Amgen and CMS follows here.

May 16, 2007

The Honorable Andrew C. von Eschenbach, M.D.
Commissioner
U.S. Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857

Dear Commissioner von Eschenbach:

The United States Senate Committee on Finance (Committee) has jurisdiction over the Medicare and Medicaid programs and, accordingly, a responsibility to the more than 80 million Americans who receive health care coverage under those programs to oversee the proper administration of the programs, including the payment for prescription drugs regulated by the Food and Drug Administration (FDA).

Last Thursday, FDA's Oncologic Drugs Advisory Committee (Advisory Committee) met to discuss the use of erythropoiesis-stimulating agents (ESAs) in cancer patients. As you know, the Advisory Committee recommended new restrictions on prescribing information for ESAs and additional clinical trials to assess the drugs' safety in light of reports of increased risk of cardiovascular disease, tumor growth, and even death associated with higher than recommended doses of the drugs.

I read with great concern the Los Angeles Times article, dated May 11, 2007, which noted that some members of the Advisory Committee suggested that Amgen Inc. (Amgen), manufacturer of the ESAs, Aranesp, Epogen and Procrit, the latter of which is marketed by Ortho Biotech Products, L.P., a subsidiary of Johnson & Johnson, "was not being upfront about all the drug's risks." What further troubled me was a Bloomberg article, also dated May 11, 2007, which reported that that the FDA was given limited access to results from company studies and Amgen did not provide complete responses to the FDA's requests for data. This troubles me because the FDA cannot do its job well if it lacks complete and accurate information.

According to Bloomberg, Amgen responded that academic researchers often do not make full results available to the FDA. Through my investigations, I also have learned that there are certain types of information that manufacturers are not required to provide to the FDA, although they may submit such information voluntarily. However, FDA should have access to any data or information that is relevant to its assessment of the safety and efficacy of a drug.

In other letters to you, I have emphasized the importance of providing FDA's advisory committees with the relevant and truthful information they need to perform their advisory function. It is even more essential that the FDA works with a full deck of cards because it decides what safety actions to take based on the data and information available to the agency.

In light of the concerns raised during the Advisory Committee meeting on ESAs, it appears that the FDA may need tools that will enable the agency to obtain access to additional data and information from manufacturers so that informed decisions can be made about a drug's safety and efficacy. The U.S. Senate passed the Food and Drug Administration Revitalization Act last week, but the House of Representatives has not yet acted, which gives Congressional leaders another opportunity to consider new and important measures to strengthen the hand of the FDA in looking out for American consumers.

Accordingly, I am requesting that the FDA arrange a meeting with my Committee staff by no later than May 31, 2007, to discuss ways to ensure that the FDA receives all of the relevant and truthful information that it requires to perform its duties. Please have your staff prepared to discuss FDA's data needs and the issues and concerns raised in this letter. In particular, they should be prepared to respond to the following questions:

What data or information that is not already available to the FDA does the agency believe should be available for purposes of evaluating a drug's safety or efficacy or the integrity of the data that is submitted to the FDA?

Please describe the type(s) of data that the FDA requested from Amgen regarding ESAs and discuss the manufacturer's explanation for not providing that data to the FDA and submitting incomplete responses. What is the relevance of the data to FDA's assessment of the safety of ESAs?

The FDA announced that its Cardiovascular and Renal Drugs Advisory Committee would meet this fall to discuss the safety of ESAs in the ESRD setting. Given the reported incomplete responses to the FDA's data request, do you anticipate similar problems with obtaining data from the manufacturer for the Cardiovascular and Renal Drugs Advisory Committee meeting?

Last month, the Wall Street Journal reported that Amgen may have promoted use of Aranesp and Epogen to improve a patient's quality of life and that the manufacturer had conducted some studies in that area. When did the manufacturer inform the FDA of those studies? Has the FDA requested data from the manufacturer regarding those studies, and if so, has the manufacturer submitted the data as requested to the FDA?

I look forward to your cooperation and assistance on this important matter. Please have your staff contact my Committee staff to schedule a meeting.

Sincerely,

Charles E. Grassley
Ranking Member
Committee on Finance

May 16, 2007

Mr. Kevin Sharer
Chairman, Chief Executive Officer and President
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1799

Dear Mr. Sharer:

The United States Senate Committee on Finance (Committee) has jurisdiction over the Medicare and Medicaid programs and, accordingly, a responsibility to the more than 80 million Americans who receive health care coverage under those programs to oversee the proper administration of the programs, including the payment for prescription drugs regulated by the Food and Drug Administration (FDA).

Last Thursday, FDA's Oncologic Drugs Advisory Committee (Advisory Committee) met to discuss the use of erythropoiesis-stimulating agents (ESAs) in cancer patients. As you know, the Advisory Committee recommended new restrictions on prescribing information for ESAs and additional clinical trials to assess the drugs' safety. In addition, on May 14, 2007, the Centers for Medicare and Medicaid Services (CMS) released its proposed coverage decision memorandum regarding the clinical conditions for Medicare reimbursement for ESAs.

Several news articles have raised concerns not only about Medicare's payment system creating incentives for using higher doses of ESAs than are necessary, but also the impact of marketing and supply contracts between ESA manufacturers and dialysis providers on the utilization of ESAs. The Wall Street Journal reported that Amgen Inc. (Amgen) may have promoted the use of Aranesp and Epogen for improving a patient's quality of life without sufficient evidence for the claim. The New York Times reported on profits that doctors make through rebates they may receive from purchasing the drugs from Amgen and Johnson & Johnson and collecting payments from Medicare and private insurers, which are often above the purchase price.

In addition, I read with great concern the Los Angeles Times article, dated May 11, 2007, which noted that some members of the Advisory Committee suggested that Amgen "was not being upfront about all the drug's risks." What further troubled me was a Bloomberg article, also dated May 11, 2007, which reported that the FDA was given limited access to results from company studies and Amgen did not provide complete responses to the FDA's requests for data. It is essential that the FDA receive complete and accurate information in order for the agency to take appropriate and timely actions in response to emerging safety concerns.

Accordingly, I am requesting that Amgen arrange a briefing for my Committee staff by May 31, 2007, to discuss the issues and concerns that have been reported in the media over the last several weeks regarding the marketing and safety of ESAs. In addition, please be prepared to address the following questions:

Please describe the type(s) of data that the FDA requested from Amgen. Were the data related to the safety and/or efficacy of the ESAs?

Did Amgen provide complete responses to FDA's data requests? If not, please provide an explanation for submitting incomplete responses.

In its proposed coverage decision memorandum, CMS expressed concern that a number of trials of ESA treatment have been terminated, suspended, or otherwise not completed. Has Amgen sponsored any trials of ESA treatment that have been terminated, suspended, or otherwise not completed that showed evidence of serious adverse effects? If so, have the results from those trials been made available to the FDA? If not, please explain why study results were withheld from the FDA.

On April 10, 2007, The Wall Street Journal reported that Amgen conducted some studies related to the use of Aranesp and Epogen to improve a patient's quality of life. When did Amgen inform the FDA of those studies? Has the FDA requested data regarding those studies? If so, did Amgen submit the data as requested?

The Wall Street Journal also reported $500 million a year in sales from doctors who prescribed Aranesp "off label" to treat anemia in cancer patients who were no longer receiving chemotherapy. In light of the increased risk of serious adverse effects, including death, associated with the use of ESAs in this patient population, what actions, if any, has Amgen taken to ensure that doctors and patients are informed of the new safety risks?

Any documents responsive to the issues and questions to be discussed at the briefing should be sent to the Committee prior to the briefing via electronic transmission in PDF format. In cooperating with the Committee's review, no documents, records, data or information related to these matters shall be destroyed, modified, removed or otherwise made inaccessible to the Committee.

I look forward to your cooperation and assistance on this important matter. Thank you in advance for providing the name and contact information, including an e-mail address, for a person who will act as the point of contact for Amgen during the Committee's review by no later than May 22, 2007.

Sincerely,

Charles E. Grassley
Ranking Member

Committee on Finance

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