November 17, 2006
Amgen, NKF and the Dialysis Killing Fields
Anyone who has ever attended a Food and Drug Administration advisory committee meeting knows about the incestuous relationshp between patient groups and drug companies. When a new drug is up for approval, the public comment period of the meeting is almost always dominated by patient-advocates offering their desperate stories suggesting how much they need this drug. In many cases, it's no doubt true, and it is hard not to feel empathy for these people. But I always wished that they had shown up there on their own, and did not disclose, as is required by the agency, that their plane fare and hotel bills were paid for by the company sponsoring the new product.
I'm reminded of that this afternoon after the Lancet published a commentary today on a newly published clinical trial showing high doses of Amgen's Epogen may be killing people on dialysis (see yesterday's GoozNews). It was written by Robert Steinbrook of Dartmouth Medical College. Here's a few selected sections:
There is no way to know with certainty why the hemoglobin concentrations in half the patients undergoing dialysis in the US are maintained at values higher than those specified by the FDA. One possible explanation is reimbursement methods and financial incentives that reward increased use of epoetin. Dialysis facilities can make more money from separately billed medications such as epoetin than from dialysis itself.
He then points out that the National Kidney Foundation recently amended its guidelines for dialysis care to increase the target hemoglobin level. Surprise, the higher level is the same as the target level in the study that showed a 34 percent increase in heart attacks and strokes over people kept at lower levels!
They (the NKF) have been questioned for their reliance on expert opinion and because of the close relations between the Foundation, the Kidney Disease Outcomes Quality Initiative (KDOQI) that formulates its recommendations, and the drug industry. In fiscal 2005, according to its annual report, the Foundation received $19.7 million -- 57 percent of its total support -- from various "corporate and organizational Partners." In calendar year 2005, it received $4.1 million from Amgen and $3.6 million from Ortho Biotech, a subsidiary of Johnson & Johnson, the current marketers of epoetin products in the US."
He ends with a plea for the National Institutes of Health or the Agency for Healthcare Research and Quality to write new guidelines. We don't need new guidelines. We need a Center for Medicare and Medicaid Services, which pays for dialysis, that will use the evidence that is already in the literature to crack down on excessive use of this drug.
Outgoing Ways and Means chairman Bill Thomas, who to his credit has been after CMS to change this policy, sent another letter to CMS yesterday demanding a change in policy. Pete Stark (D-CA), who has been fighting this battle for over a decade, will soon take the health subcommittee under Charlie Rangel's leadership.
The evidence is in. CMS reimbursement policy is killing people, all to benefit Amgen and its lobbyists. How long will it take the agency to respond?
Posted by gooznews at November 17, 2006 04:41 PMHe then points out that the National Kidney Foundation recently amended its guidelines for dialysis care to increase the target hemoglobin level. Surprise, the higher level is the same as the target level in the study that showed a 34 percent increase in heart attacks and strokes over people kept at lower levels!
Merrill, I've written before about the travesty that evolved over 2 decades ago promoting rDNA insulin. The modus operandi you describe in the article evolved from Eli Lilly's roadmap to promote their rDNA insulin. Each minute action--when it met with little opposition--formed a building block for the next action. Where the Kidney study group RAISED the guidelines--to suggest that more drug is needed to meet the guidelines, the diabetes study group (DCCT) LOWERED numbers--thus requiring tighter control--not necessarily MORE drug (heaven knows, the drug is cheap to manufacture), but all the accoutrements needed to maintain numbers. Amended guidelines also provided "wiggle room" for both the medical professional and the industry.
What worked for Lilly in the early 80s has become (an unwritten) primer for disease maintenance and drug sales. Unfortunately, I have not been able to encourage anyone to re-visit history with a view to changing the status quo. With almost daily stories of the corrupt intertwining of industry-government-professionals as it pertains to medicine, I guess the old saw illustrates MY dilemma (no one to check out the roots of this behavior): "It's hard to talk about the draining the swamp when you're up to your ass in alligators."
Posted by: Melody at November 18, 2006 07:50 AMRegarding the comment that Epogen [containing recombinant human erythropoietin (EPO) glycoprotein expressed in Chinese hamster ovary (CHO) cell culture] is "cheap to manufacture," I do not believe this is the case. Both Amgen, which manufactures Epogen and bulk (unformulated) EPO for further manufacture of Procrit by Ortho/J&J, and Ortho/J&J which makes its own EPO under license from Amgen for Eprex, which it markets internationally, culture transformed CHO cells in roller bottles. This involves thousands, maybe even 10s of thousands, of individual bottles on automated racks with rollers so that they slowly roll (with culture media flowing over the layer of EPO-expressing cells that attach to the surface of the bottles). I believe both Amgen and Ortho/J&J have their own EPO-dedicated manufacturing facilities in Puerto Rico.
This is old, now relatively ancient, biopharmaceutical manufacturing technology (and EPO is a decades-old product). These companies still cost-effectively manufacture EPO using this old technology primarily because EPO is highly potent (compared to some other recombinant proteins, e.g., monoclonal antibodies ) and the prices they get for the products.
However, a number of companies are actively developing biogeneric versions of EPO to be ready when Amgen's patents expire. These companies expect to compete on the basis of price, with manufacturing their primary expense. All of these companies are reported to be using much more efficient, higher yield, cost-effective, etc. modern bioreactors for CHO cell culture, and some are using truly novel manufacturing platform technologies (expression systems), e.g., transgenic animals.
Thus, the per dose cost for Epogen manufacture is probably high, relative to many other biopharmaceuticals. However, generally, the costs of manufacture have little to do with the prices of most biopharmaceuticals. Rather, prices are usually based on cost-benefit analysis -- essentially what the market, particularly insurers, will bear/pay, with use of biopharmaceuticals generally significantly reducing the overall cost of treatment and providing more effective treatment than alternatives, including not using the product, such that use of biopharmaceuticals is welcome (or not using them is unacceptable in highly-developed countries).
Ronald A. Rader
President / Author - Biopharmaceutical Products in the U.S. and European Markets
Biotechnology Information Institute
1700 Rockville Pike, Suite 400
Rockville, MD 20852
Phone: 301-424-0255
E-mail: ron@biopharma.com
Web sites: www.biopharma.com; www.biopharmacopeia.com;
www.followonproteins.com; www.bioinfo.com
Of note, unless I missed something none of the NEJM articles particularly referred to the cost of EPO to the health care system or the specific excess costs of more usage of EPO. Why not? Perhaps to maintain the illusion (useful to AMGEN and Pharma and the NEJM) that these are academic questions (independent of economics) to be decided by scholarship. Even if
the studies were completely favorable for more EPO usage does that mean that the price of EPO and the profits made on it are irrelevant to the NEJM, medical profession or public. Why is the paradigm story of the biotech revolution that of EPO still only of interest to Merril Goozner or at least reported on by Merril? My own opinions,
1. a Key Opinion Leadership and med education industry subsidized by pharma.
2. a media and body politic equally subsidized.
3. With the kind of profit margin AMGEN has a little goes a long way in keeping things quiet.
I would appreciate any resources suggesting Procrit causes blood clots in the lungs, pure red cell aplasia or sudden, precipitous drop in red blood cells and/or cardiac arrest.
Posted by: maury hexamer at November 22, 2006 06:18 PMReply to readers:
Sorry, Maury, but I don't have any information on the problem of lung blood clots from Procrit, but maybe some other readers would like to chime in.
As far as Dr. Rader's comments concerning cost of manufacturing are concerned, Amgen reports its "cost of goods sold" in its SEC filings the same as every other biopharmaceutical company. It essentially has two best-selling drugs and a few others than don't sell very well. So it's fair to assume that Epogen/Aranesp/Neupogen (all biopharmaceuticals made with CHO cell technology) are the bulk of its manufacturing costs. They report those costs at about 17 percent of their sales dollar, less than the percentage devoted to R&D, sales and marketing, and half the level of their profits. That said, it is somewhat larger than what the average pharmaceutical company spends, probably because it is more complicated to make proteins than small molecules.
Merrill