Dear Commissioner von Eschenbach:
The United States Senate Committee on Finance (Committee) has jurisdiction over theMedicare and Medicaid programs and, accordingly, a responsibility to the more than 80 millionAmericans who receive health care coverage under those programs to oversee the properadministration of the programs, including the payment for prescription drugs regulated by theFood and Drug Administration (FDA).
Last Thursday, FDA's Oncologic Drugs Advisory Committee (Advisory Committee) metto discuss the use of erythropoiesis-stimulating agents (ESAs) in cancer patients. As you know,the Advisory Committee recommended new restrictions on prescribing information for ESAsand additional clinical trials to assess the drugs' safety in light of reports of increased risk ofcardiovascular disease, tumor growth, and even death associated with higher than recommendeddoses of the drugs.
I read with great concern the Los Angeles Times article, dated May 11, 2007, whichnoted 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 byOrtho Biotech Products, L.P., a subsidiary of Johnson & Johnson, "was not being upfront aboutall 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 studiesand Amgen did not provide complete responses to the FDA's requests for data. This troubles mebecause 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 makefull results available to the FDA. Through my investigations, I also have learned that there arecertain types of information that manufacturers are not required to provide to the FDA, althoughthey may submit such information voluntarily. However, FDA should have access to any data orinformation that is relevant to its assessment of the safety and efficacy of a drug.
In other letters to you, I have emphad the importance of providing FDA's advisorycommittees with the relevant and truthful information they need to perform their advisoryfunction. It is even more essential that the FDA works with a full deck of cards because itdecides 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, itappears that the FDA may need tools that will enable the agency to obtain access to additionaldata and information from manufacturers so that informed decisions can be made about a drug'ssafety and efficacy. The U.S. Senate passed the Food and Drug Administration RevitalizationAct last week, but the House of Representatives has not yet acted, which gives Congressionalleaders another opportunity to consider new and important measures to strengthen the hand ofthe FDA in looking out for American consumers.
Accordingly, I am requesting that the FDA arrange a meeting with my Committee staffby no later than May 31, 2007, to discuss ways to ensure that the FDA receives all of therelevant and truthful information that it requires to perform its duties. Please have your staffprepared to discuss FDA's data needs and the issues and concerns raised in this letter. Inparticular, they should be prepared to respond to the following questions:
1. What data or information that is not already available to the FDA does the agency believeshould be available for purposes of evaluating a drug's safety or efficacy or the integrityof the data that is submitted to the FDA?
2. Please describe the type(s) of data that the FDA requested from Amgen regarding ESAsand discuss the manufacturer's explanation for not providing that data to the FDA andsubmitting incomplete responses. What is the relevance of the data to FDA's assessmentof the safety of ESAs?
3. The FDA announced that its Cardiovascular and Renal Drugs Advisory Committeewould meet this fall to discuss the safety of ESAs in the ESRD setting. Given thereported incomplete responses to the FDA's data request, do you anticipate similarproblems with obtaining data from the manufacturer for the Cardiovascular and RenalDrugs Advisory Committee meeting?
4. Last month, the Wall Street Journal reported that Amgen may have promoted use ofAranesp and Epogen to improve a patient's quality of life and that the manufacturer hadconducted some studies in that area. When did the manufacturer inform the FDA ofthose studies? Has the FDA requested data from the manufacturer regarding thosestudies, 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 haveyour staff contact my Committee staff to schedule a meeting.
Sincerely,
Charles E. Grassley Ranking Member Committee on Finance
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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 theMedicare and Medicaid programs and, accordingly, a responsibility to the more than 80 millionAmericans who receive health care coverage under those programs to oversee the properadministration of the programs, including the payment for prescription drugs regulated by theFood and Drug Administration (FDA).
Last Thursday, FDA's Oncologic Drugs Advisory Committee (Advisory Committee) metto discuss the use of erythropoiesis-stimulating agents (ESAs) in cancer patients. As you know,the Advisory Committee recommended new restrictions on prescribing information for ESAsand additional clinical trials to assess the drugs' safety. In addition, on May 14, 2007, theCenters for Medicare and Medicaid Services (CMS) released its proposed coverage decisionmemorandum regarding the clinical conditions for Medicare reimbursement for ESAs.
Several news articles have raised concerns not only about Medicare's payment systemcreating incentives for using higher doses of ESAs than are necessary, but also the impact ofmarketing and supply contracts between ESA manufacturers and dialysis providers on theutilization of ESAs. The Wall Street Journal reported that Amgen Inc. (Amgen) may havepromoted the use of Aranesp and Epogen for improving a patient's quality of life withoutsufficient evidence for the claim. The New York Times reported on profits that doctors makethrough 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 thepurchase 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 notbeing 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 fromcompany 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 totake appropriate and timely actions in response to emerging safety concerns.
Accordingly, I am requesting that Amgen arrange a briefing for my Committee staff byMay 31, 2007, to discuss the issues and concerns that have been reported in the media over thelast several weeks regarding the marketing and safety of ESAs. In addition, please be preparedto address the following questions:
1. Please describe the type(s) of data that the FDA requested from Amgen. Were the datarelated to the safety and/or efficacy of the ESAs?
2. Did Amgen provide complete responses to FDA's data requests? If not, please providean explanation for submitting incomplete responses.
3. In its proposed coverage decision memorandum, CMS expressed concern that a numberof 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, havethe results from those trials been made available to the FDA? If not, please explain whystudy results were withheld from the FDA.
4. On April 10, 2007, The Wall Street Journal reported that Amgen conducted some studiesrelated to the use of Aranesp and Epogen to improve a patient's quality of life. When didAmgen inform the FDA of those studies? Has the FDA requested data regarding thosestudies? If so, did Amgen submit the data as requested?
5. The Wall Street Journal also reported $500 million a year in sales from doctors whoprescribed Aranesp "off label" to treat anemia in cancer patients who were no longerreceiving 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 newsafety risks?
Any documents responsive to the issues and questions to be discussed at the briefingshould 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 relatedto these matters shall be destroyed, modified, removed or otherwise made inaccessible to theCommittee.
I look forward to your cooperation and assistance on this important matter. Thank you inadvance for providing the name and contact information, including an e-mail address, for aperson who will act as the point of contact for Amgen during the Committee's review by no laterthan May 22, 2007.
Sincerely,
Charles E. Grassley United States Senator Ranking Member of the Committee on Finance
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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 theMedicare and Medicaid programs and, accordingly, a responsibility to ensure that drugs andservices provided to the 80 million beneficiaries of these programs are safe and effective and arepurchased in a fiscally responsible manner.
The Centers for Medicare and Medicaid Services (CMS) is responsible for makingcoverage 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 renaldisease (ESRD) related care. ESRD spending accounted for nearly $7.9 billion of total Medicarespending in 2005. One of the central services within the ESRD program is the administration oferythropoiesis-stimulating agents (ESAs) for the treatment of anemia in patients with chronickidney failure. Outside of the ESRD program, Medicare and Medicaid also make significantexpenditures on ESAs for chemotherapy-induced anemia in cancer patients. According to theGovernment 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., asubsidiary of Johnson & Johnson.
Although ESAs have improved the quality of life for thousands of kidney patients, theGAO report cites concerns that the Medicare payment system has created incentives for usingmore doses of ESAs than are necessary. Medicare pays one rate for dialysis and other ESRDservices; 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 ofESAs. The Medicare Payment Advisory Commission (MedPAC) also recommends that paymentbe bundled to control costs and promote quality care. In addition, MedPAC has recommendedimplementation of a quality incentive payment policy for providers of outpatient dialysisservices.
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 ofincreased risks of death, blood clots, strokes, heart attacks, and tumor growths when ESAs aregiven in higher than recommended doses. As a result of these studies, on March 9, 2007, theFDA issued a public health advisory to inform doctors and patients of the new safety informationregarding Aranesp, Epogen, and Procrit. Furthermore, the product labeling for ESAs have beenrevised to include new warnings and modifications to the dosing instructions.
Accordingly, I am requesting that CMS arrange a briefing for my Committee staff by nolater than April 27, 2007, to address the following questions, among other things:
1. In light of new warnings from the FDA regarding ESAs, CMS announced that it wouldclosely review all Medicare policies related to the administration of ESAs. What is thestatus of CMS's review and what specific actions are being considered to ensure thesafety of Medicare and Medicaid beneficiaries and prevent the overuse of ESAs?
2. Medicare Part B currently requires that physicians report hemoglobin or hematocritlevels for certain chronic kidney disease patients, but not for cancer patients. Section 110of the Tax Relief and Health Care Act of 2006 requires that all Part B claims submittedfor drugs that are furnished to individuals on or after Jan. 1, 2008, in connection withchemotherapy include the hemoglobin or hematocrit levels for those individuals. What isthe status of implementation of this new requirement?
3. On April 1, 2006, CMS implemented a national monitoring policy for use of ESAs inMedicare beneficiaries with ESRD. According to information posted on CMS's website,the previous methodology for monitoring ESA claims "was implemented with limitedscientific analysis." What was the scientific support for CMS's current monitoringpolicy? Did CMS consider the funding source of the studies and/or other scientificsupport upon which the agency relied in developing the current monitoring policy? DidCMS review the validity and impartiality of the scientific evidence?
4. The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 requiredCMS to issue a report and conduct a demonstration of a system for bundling payment ofESAs with other ESRD items and services under a single rate. CMS's report was due inOctober 2005, but according to GAO testimony dated December 6, 2006, both the reportand the demonstration testing of the feasibility of a bundled rate have been delayed.
What is the status of the report and demonstration? What are the reasons for the delays?Thank you for your prompt attention to this matter.
Sincerely,
Charles E. Grassley United States Senator Ranking Member of the Committee on Finance
