Sen. Grassley seeks to empower FDA to access drug-risk information from drug makers

WASHINGTON — 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:

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:

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

April 10, 2007

Leslie Norwalk

Acting Administrator

Centers for Medicare and Medicaid Services

Department of Health and Human Services

200 Independence Avenue, SW

Washington, DC 20201

Dear Acting Administrator Norwalk:

The United States Senate Committee on Finance (Committee) has jurisdiction over the Medicare and Medicaid programs and, accordingly, a responsibility to ensure that drugs and services provided to the 80 million beneficiaries of these programs are safe and effective and are purchased in a fiscally responsible manner.

The Centers for Medicare and Medicaid Services (CMS) is responsible for making coverage determinations for a wide variety of drugs, biologics, devices, and medical services. One of the most significant expenditures within the Medicare program is for end-stage renal disease (ESRD) related care. ESRD spending accounted for nearly $7.9 billion of total Medicare spending in 2005. One of the central services within the ESRD program is the administration of erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in patients with chronic kidney failure. Outside of the ESRD program, Medicare and Medicaid also make significant expenditures on ESAs for chemotherapy-induced anemia in cancer patients. According to the Government Accountability Office (GAO), Medicare spent $2 billion in 2005 for Epogen alone, an ESA manufactured by Amgen, Inc. (Amgen). Amgen also manufactures two other ESAs, Aranesp and Procrit, the latter of which is marketed by Ortho Biotech Products, L.P., a subsidiary of Johnson & Johnson.

Although ESAs have improved the quality of life for thousands of kidney patients, the GAO report cites concerns that the Medicare payment system has created incentives for using more doses of ESAs than are necessary. Medicare pays one rate for dialysis and other ESRD services; however, it pays for ESAs separately on a per service basis. According to the GAO, bundling all ESRD drugs and services under a single rate would encourage more prudent use of ESAs. The Medicare Payment Advisory Commission (MedPAC) also recommends that payment be bundled to control costs and promote quality care. In addition, MedPAC has recommended implementation of a quality incentive payment policy for providers of outpatient dialysis services.

An overuse or inefficient use of ESAs is not only a financial concern to the Committee, but also a major patient safety concern. I am troubled by the findings in recent clinical studies of increased risks of death, blood clots, strokes, heart attacks, and tumor growths when ESAs are given in higher than recommended doses. As a result of these studies, on March 9, 2007, the FDA issued a public health advisory to inform doctors and patients of the new safety information regarding Aranesp, Epogen, and Procrit. Furthermore, the product labeling for ESAs have been revised to include new warnings and modifications to the dosing instructions.

Accordingly, I am requesting that CMS arrange a briefing for my Committee staff by no later than April 27, 2007, to address the following questions, among other things:

Thank you for your prompt attention to this matter.

Sincerely,

Charles E. Grassley

Ranking Member

Committee on Finance