December 8, 2006 - The Boston Globe published an article on the front page that outlined the growing concern and scrutiny over the care of kidney patients due to behaviors surrounding one drug company's monopoly. Article from The Boston Globe.

December 7, 2006 - Several articles are reporting on yesterday's hearing before the Ways & Means Committee on patient safety and quality issues in ESRD:

The Boston Globe

The Los Angeles Times

Reuters


"You seriously need to consider that your payment policy is killing people," House Ways and Means Committee chairman Bill Thomas told Medicare chief medical officer Dr. Barry Straube , who flanked acting Medicare administrator Leslie V. Norwalk at a witness table. (Boston Globe)

Testimony and transcripts (not yet available) of the hearing can be accessed from the the Ways and Means Committtee web page. (The internet audio feed did not function during portions of the hearing. More reporting will follow when transcripts become available.)

Statements from Amgen, AAKP, and a Nov. 17 blog entry from Gooznews.

December 6, 2006 - The House Ways and Means Committee, frequently the setting for bitter partisanship under Chairman Bill Thomas will hold its final hearing of the 109th Congress today on an issue of bipartisan interest, much to the chagrin of the kidney-dialysis-provider industry and drug manufacturer Amgen. Report from The Hill.

December 5, 2006 - The Government Accountability Office (GAO) has release a report entitled, "Bundling Medicare's Payment for Drugs with Payment for All ESRD Services Would Promote Efficiency and Clinical Flexibility". 40-page pdf file.

Medicare, the U.S. insurance program for elderly and disabled Americans, should lump the price of anemia drugs with overall payments for kidney dialysis services to improve efficiency and contain costs, according to a government report released on Tuesday. Article from Reuters.


December 4, 2006 - A U.S. congressional committee will hold a hearing on Wednesday to discuss whether to cut back Medicare payments for drugs used to treat anemia in kidney failure, such as Amgen's Epogen. Article from Reuters.

The Medicare reimbursement policy for epoetin alfa (Epogen, Amgen) to correct anemia in patients with kidney disease has seen 15 changes from July 1999 to October 2006. (Reference: Medscape Nephrology (registration required, but free)). The administration of erythropoiesis-stimulating agents (ESAs) in the United States provides a classic example of how economics drive practice. (Reference: Kidney International).

Amgen has responded to reports about the use and safety of EPOGEN and Aranesp in chronic kidney disease therapy. Press release via Yahoo. In this release, Amgen states that it only promotes the use of EPOGEN and Aranesp consistent with the FDA label.

While it is against the law for pharmaceutical companies to promote off-label use, they do strategize how to maximize reimbursement for off-label prescribing. See the abstract of this report from Decision Resources, Inc.

Once the FDA approves a drug for prescription use, they do not attempt to regulate the practice of medicine. The physician makes decisions based on her or his best judgment. It is entirely legal in the United States and in many other countries to use drugs off-label. Access to pharmaceutical industry documents have revealed marketing strategies used to promote drugs for off-label use. (Reference: Wikipedia: Off-label use)

In 2004, Warner-Lambert paid $430 million to resolve criminal and civil health care liability relating to off-label promotion. News release from the Department of Justice.


December 1, 2006 - Congressman Bill Thomas (R-CA), Chairman of the Committee on Ways and Means, today announced that the Committee will hold a hearing on safety and quality for Medicare beneficiaries with End Stage Renal Disease (ESRD). The hearing will take place on Wednesday, December 6, 2006, in the main Committee hearing room, 1100 Longworth House Office Building, beginning at 10:30 a.m. Advisory from the Ways and Means Committee.

November 30, 2006 - An expert panel of doctors for the National Kidney Foundation plans to assess whether hundreds of thousands of patients with kidney disease are being dangerously overtreated with drugs for anemia.

The decision to convene the panel comes two weeks after studies in The New England Journal of Medicine suggested that kidney patients whose anemia was more aggressively treated were more likely to die or suffer heart problems than those who were allowed to remain more anemic. Article from The New York Times (registration required, but free).


November 20, 2006 - There have been several developments since the November 16th publication of two articles on hemoglobin levels for chronic kidney patients in The New England Journal of Medicine (NEJM). These articles raised questions of increased risks for kidney patients when they are given higher doses of EPO to increase red blood cell counts to levels above current FDA recommendations.

FDA Warning on 12 gram limit: FDA Public Health Advisory On November 17, the U.S. Food and Drug Administration issued a public health advisory for Epogen, Aranesp (both made by Amgen), and Procrit (Epogen’s equivalent made by Johnson and Johnson) warning that their excessive use may lead to an increased risk of fatal heart attacks and strokes in chronic kidney patients. It says the FDA’s limit of 12 g/dl for hemoglobin should be strictly followed.

Lancet article on dialysis patient safety appears: On November 17, an article appeared in the UK medical journal The Lancet that questioned dialysis industry practices and National Kidney Foundation guidelines. The Lancet article said half of all kidney dialysis patients have their red blood cell counts boosted beyond the FDA's 12 g/dl limit.

Boston Globe November 18th article: FDA Warns on Anemia-Drug Dosing. Christopher Rowland continues in his recent series of articles on EPO use in the dialysis industry. He points out that recent articles in NEJM and Lancet raise serious public policy issues, as Medicare pays for most dialysis treatments in the U.S. He also explores conflict of interest issues, as Amgen has underwritten EPO guideline development for dialysis patients and the fact that dialysis clinics earn more profit when more EPO is given to patients.

According to The Boston Globe, the Lancet article’s author, Dr. Robert Steinbrook of Dartmouth Medical School, feels dialysis patient safety is at risk. "There is a disconnect between the prescribing information for these drugs and their use in maintaining high hemoglobin values," said the article's author, Dr. Robert Steinbrook, of. "It raises patient safety and public health concerns."

Also according to the Globe, the FDA's alert, which said the 12-gram limit should be strictly followed, casts new doubt on updated Medicare reimbursement policies approved this year that allow dialysis clinics to boost red blood cell counts to 13 g/dl.

NEJM authors appear at ASN: On November 18, the authors of CHOIR and CREATE-related articles in The New England Journal of Medicine presented their data at a special, late-breaking, clinical trials session at the American Society of Nephrology Annual Meeting in San Diego. The authors also appeared immediately afterward at a news briefing.

Among the interesting facts and questions that arose from these events were:

Higher quality of life not seen with higher hemoglobins. Both NEJM articles reported no improvement in quality of life with hemoglobin levels above the current FDA limit.

Does the data from the studies apply to dialysis patients? Both NEJM articles were on studies done on stage 3 and 4 kidney disease patients. Patients requiring dialysis are at stage 5. The articles’ authors were asked if they would like to make any distinctions or caveats about applying their data to dialysis patients. Dr. Ajay Singh replied that the FDA made no distinction between the groups in its recommendations and that he felt all stage 3, 4, and 5 patients should adhere to the FDA limit of 12 g/dl.



November 17, 2006 - Several medical news services are reporting on the articles that appeared in yesterday's New England Journal of Medicine on EPO dosing for chronic kidney disease patients:

High-Dose Anemia Drug May Have Risks - article from WebMD

Analysis: Concerns on Amgen Anemia Drug - article from UPI via Science Daily

Reversing Anemia Can Threaten Kidney Patients - article from HealthDay News via Yahoo. (link is no longer available)


November 16, 2006 - FDA to Review New Data for Dosage and Risk of EPO
Article from The Boston Globe.

A set of articles to be published today from the CHOIR and CREATE studies in the New England Journal of Medicine is spurring new scrutiny of the use of antianemia drugs (EPO) to boost red blood cell counts beyond Food and Drug Administration (FDA) recommendations.

FDA regulators are reviewing these studies and will likely issue a public health advisory to alert doctors and patients to the findings, an FDA spokeswoman said. Related article from Reuters.

Excerpt from The Boston Globe:
"In a letter to Medicare yesterday, Republican US Representative Bill Thomas of California, chairman of the House Ways and Means Committee, and Democratic Representative Pete Stark of California, ranking member of the Ways and Means subcommittee on health, said they are concerned Medicare is not doing enough to "stem the systemic abuse of Epogen, resulting in costs to taxpayers and potential health dangers to patients.""

Related article from The New York Times (registration required). Excerpt from the article:
"The amount of epoetin received by the typical American dialysis patient has nearly tripled since the early 1990s, and the average patient now gets epoetin doses similar to those given to the first group in Dr. Singh’s study (CHOIR). Meanwhile, death rates for dialysis remain higher in the United States than in Europe, where doses are comparable to the second group. About 22 percent of American patients die every year, compared with about 15 percent of patients in Europe."

Articles from The New England Journal of Medicine (NEJM):
CREATE - Normalization of Hemoglobin Level in Patients with Chronic Kidney Disease and Anemia - abstract from NEJM.

Whether complete correction of anemia in patients with stage 3 or 4 kidney disease improves cardiovascular outcome is not established. In this study, patients with an estimated glomerular filtration rate of 15 to 35 ml per minute and mild-to-moderate anemia were randomly assigned to receive treatment with erythropoietin to increase their hemoglobin levels to either normal or subnormal. The results suggest that early, complete correction of anemia does not reduce cardiovascular events.

CHOIR - Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease - abstract from NEJM.

Recombinant human erythropoietin is indicated for the correction of anemia in chronic kidney disease, but the optimal target level of hemoglobin is unknown. In this open-label study, epoetin alfa was given to achieve a high (13.5 g per deciliter) or a low (11.3 g per deciliter) target hemoglobin level. The higher target level was associated with an increased risk of adverse events without an improvement in quality of life.

Editorial - Correction of Anemia — Payoffs and Problems - extract of editorial from NEJM.


November 8, 2006 - Doctor hits FDA on Epogen oversight - article from The Boston Globe

Dr. Ajay Singh, clinical chief of the renal division at Brigham and Women's Hospital in Boston, oversaw a study that linked agressive use of EPO to an increased risk of fatal heart attacks and stokes. The article appears atop the Business section of today's Boston Globe.

An excerpt:
"If the government's not out there protecting this vulnerable population, who is?" said Singh, an associate professor at Harvard Medical School . He suggested that regulators' inaction is linked to the influence of pharmaceutical and dialysis industries, but did not cite any companies by name.

"There is lobbying going on. There's money being thrown in that is desensitizing people to what is going on," he said.

According to data gathered by the nonprofit Center for Responsive Politics , which tracks lobbying expenditures, Amgen spent $5.7 million lobbying Congress and federal agencies in 2005. DaVita Inc., the nation's second-largest for-profit dialysis chain, spent $380,000, and Fresenius Medical Care, the largest dialysis chain, spent $160,000. Kidney Care Partners, an industry group, spent $1 million, according to the center.


October 24, 2006
Some See Profiteering in Dialysis Clinics' Use of EPO
Article from The Boston Globe.

The method most dialysis clinics use to give patients EPO may needlessly cost the federal government as much as $537 million annually while generating additional profits for its manufacturer Amgen and the dialysis clinics that administer it under the Medicare program.

About 95 percent of the nation's 325,000 dialysis patients receive Epogen™ intravenously, but studies have shown dialysis clinics could use 30 percent less if it was administered subcutaneously. Scientific studies show that Epogen remains in the body longer when injected, requiring a lower dose.

Article summary from Kaiser Network.

See this free, full-text editorial and a meta-analysis of IV vs. subcutaneous EPO administration from the September 2002 issue of the American Journal of Kidney Diseases.

The Food and Drug Administration last year allowed Amgen to change the wording on the Epogen label to indicate intravenous delivery is preferred because of a rare and dangerous disorder called pure red cell aplasia (PRCA) that was found in 175 patients. However, an article in the June 2005 issue of Kidney International strongly suggested that the increased incidence of PRCA in dialysis patients treated with epoetins was due to materials leaching from uncoated rubber stoppers in prefilled syringes.

Here is a RenalWEB news summary of the cases of pure red cell aplasia (PRCA) that were seen in dialysis patients in 1998-2003.

According to this article from Motley Fool, Amgen is one of the most profitable companies in any industry. In 1999, when EPO was responsible for nearly all its income, Amgen's gross margins were 88%, which means that each $100 in EPO sales revenue cost Amgen $12 to manufacture, market, and distribute.

Dialysis treatments for end-stage renal disease are the only medical procedure covered by Medicare regardless of the age of the beneficiary. Since 1989, Amgen has had the only anti-anemia drug available in the U.S. for treating dialysis patients. See this December 2005 background article from The New York Times.

October 20, 2006
Fresenius Medical Care Deal With Amgen Blocks Roche

Article from The New York Times (registration required, but free).

Fresenius Medical Care selected Amgen as its sole supplier of anemia drugs, effectively cutting out potential competitor Roche.

A New York Times excerpt:

"Dr. Ben Lipps, chief executive of Fresenius, said that his company “selected Amgen as our sole supplier based on more than 10 years of demonstrated clinical efficacy and safety with Epogen.” Analysts said Fresenius probably used the looming threat from Roche to extract a bigger discount from Amgen in return for making it the sole suppplier."

Related articles from Reuters (link is no longer available)and Los Angeles Business Journal  (registration required).

Amgen has an effective monopoly on epoetins in the U.S. dialysis marketplace since 1989. In 2004, Amgen won as many as 12 extra years of patent protection, which will potentially keep the price high until 2016 - unless a competitor, such as Roche, can break through Amgen's patent defending lawsuits. Amgen's lawsuit against Roche is entering its discovery phase and Roche is concurrently seeking FDA approval for C.E.R.A., its anti-anemia drug. The trial appears set for September 2007.

October 19, 2006
Fresenius Medical Care Strikes Supply Deal with Amgen
News item from Biowire via Genetic Engineering News.

The new sourcing and supply agreement runs from October 1, 2006 to December 31, 2011, and replaces the previous product purchase agreement between the parties. In addition, the companies will explore collaborations to develop new product formulations to further enhance standards of care.

October 13, 2006
Amgen's Enemies
Article from Forbes (registration required, but free). Doctors are rebelling against its marketing practices, dissidents think Medicare is too generous to it and competition looms. An excerpt:

"Some of the guidelines that Medicare relies on were set by a committee of the National Kidney Foundation, whose work was principally funded by Amgen. "Amgen essentially purchased the pseudoscience that went into raising these hematocrit guidelines in the medical literature," bristles Merrill Goozner, a director at the Center for Science in the Public Interest. As a result, he says, Amgen "is ripping off Medicare.""

Related editor's comment in Forbes.

September 15, 2006
Blog from The Huffington Post©: The Amgen Rip-Off

Merrill Goozner, author of "The $800 Million Pill: The Truth Behind the Cost of New Drugs", comments on the article in Health Affairs about Medicare EPO policy.

Background info on "The $800 Million Pill".

September 14, 2006
Boston GlobeReports on the Unpublished and Halted Studies Showing Increased Death Risk with Higher Doses of EPO

In a front page story, Christopher Rowland (CRowland@globe.com) reports that kidney dialysis patients covered by Medicare are receiving escalating doses of Epogen™, despite growing evidence that aggressive treatment raises the risk of fatal heart attacks and strokes.

September 12, 2006
An article appears in the latest issue of Health Affairs that examines Medicare's EPO policies and suggests that untested research findings have been translated too quickly into policy that encourages large epoetin doses.

The authors of the the paper are from the Medical Technology and Practice Patterms Institute (MTPPI) (web site). They conclude, “We propose exclusive public funding for guideline development for drugs used to treat chronic conditions covered by Medicare PartD.”

Abstract of the article from Health Affairs.

In April 2006, chairman of the House Ways and Means Committee Bill Thomas wrote to CMS Administrator Mark McClellan about CMS's dismissal of FDA drug labeling criteria. The letter specifically (2-page pdf) mentions Epogen.

In a January 2006 editorial in the American Journal of Kidney Diseases, Dr. Patrick Parfrey writes:
"Until (more studies) are completed, target hemoglobin levels greater than 11 to 12 g/dL cannot be recommended for rHuEPO therapy because of lack of evidence for benefit, potential for increased risk for thrombogenic events, and high cost of small improvements in quality of life."

Scientific Studies Showing Benefits of Subcutaneous EPO Administration

Feb. 17, 2006
20% Increase in EPO Dose Required To Maintain Hemoglobin Targets after Conversion from a Subcutaneous to IV Formulation (link is no longer available)

Abstract from The Annals of Pharmacotherapy.

November 22, 2005
Effect of Switching from Subcutaneous to Intravenous Administration of EPO

Abstract from Nephron Clinical Practice. Overall, erythropoietin- doses increased by 26% when patients were converted from subcutaneous to intravenous administration.

November 14, 2005
Results on Subcutaneous NeoRecormon® (epoetin beta) for 1000 Patients in Europe

Roche press release via MedicalNewsToday.

Oct. 25, 2005
Study of Different Frequencies of EPO Administration by IV and SubQ Routes in Dialysis Patients

Advance Access abstract from Nephrology Dialysis Transplantation.

And finally....

January 11, 2005
Lowering Health Care Costs a Top Priority for Americans, Survey Finds

This message has been edited. Last edited by: Leigh,