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Amgen Announces Update to U.S. Prescribing Information for Aranesp® and EPOGEN®

Amgen Inc. (NASDAQ:AMGN) today announced the U.S. Food and Drug Administration (FDA) has approved updated safety information, including an updated boxed warning in the labeling information for the class of drugs known as erythropoiesis-stimulating agents (ESAs), including Aranesp® (darbepoetin alfa) and EPOGEN® (Epoetin alfa). The updated boxed warning states that ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid and cervical cancers, when dosed to target a hemoglobin of = 12 g/dL. In the "Increased Mortality and/or Tumor Progression” warning section of the updated labeling, the interim results of the Preoperative Epirubicin Paclitaxel Aranesp (PREPARE) study in neo-adjuvant breast cancer were added as well as follow up data from the Gynecologic Oncology Group study in cervical cancer. Amgen and Johnson & Johnson have submitted all available clinical data to the FDA including the data from these two study studies now reflected in the product labeling, as well as data from other informative controlled clinical studies with ESAs in the oncology setting. In general, these results have not changed the benefit-risk profile significantly of ESAs in this setting from previously available data discussed at the May 4, 2004, and May 10, 2007, Oncologic Drugs Advisory Committee (ODAC) meetings. Amgen will address the science and safety of ESAs in oncology, including these new data, at an upcoming ODAC meeting next week on Thursday, March 13, 2008. Amgen is informing healthcare professionals about the revisions to the U.S. prescribing information through a joint "Dear Healthcare Professional” letter with Ortho Biotech and will post the letter along with the updated prescribing information on Amgen’s Web site, http://www.amgen.com. "Amgen is committed to ensuring physicians and patients have the latest information about ESAs in order to make appropriate treatment decisions,” said Sean Harper, Amgen’s Chief Medical Officer. "Last year, we communicated the new safety information in several ways, including disseminating DHCP letters, posting the new labeling on our Web site, focusing promotional activity from March until the May ODAC on warnings and safety data, and hosting ongoing briefings with the oncology community.” Amgen’s ongoing risk management activities includes working with the FDA to design additional pharmacovigilance studies to address safety concerns around ESAs, developing a patient medication guide to communicate the benefit/risk of ESAs, and continuing to publicly communicate updates on ESAs to the public and oncology community. Important Aranesp and EPOGEN Safety Information WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL. Cancer: ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of = 12 g/dL. The risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to target a hemoglobin of < 12 g/dL. To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions. Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy. Discontinue following the completion of a chemotherapy course. Aranesp is contraindicated in patients with uncontrolled hypertension. About Amgen Amgen discovers, develops, manufacturers and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science’s promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people’s lives. To learn more about our pioneering science and our vital medicines, visit http://www.amgen.com. Forward-Looking Statements This news release contains forward-looking statements that involve significant risks and uncertainties, including those discussed below and others that can be found in our Form 10-K for the year ended Dec. 31, 2007, and in our periodic reports on Form 10-Q and Form 8-K. Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. The Company’s results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments (domestic or foreign) involving current and future products, sales growth of recently launched products, competition from other products (domestic or foreign) and difficulties or delays in manufacturing our products. In addition, sales of our products are affected by reimbursement policies imposed by third-party payors, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and health care cost containment as well as U.S. legislation affecting pharmaceutical pricing and reimbursement. Government and others’ regulations and reimbursement policies may affect the development, usage and pricing of our products. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. We or others could identify safety, side effects or manufacturing problems with our products after they are on the market. Our business may be impacted by government investigations, litigation and product liability claims. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future products and limits on supply may constrain sales of certain of our current products and product candidate development. In addition, we compete with other companies with respect to some of our marketed products as well as for the discovery and development of new products. Discovery or identification of new product candidates cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate will be successful and become a commercial product. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers.

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erschienen am 07.03.2008 um 21:32 Uhr

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Gee, could it be that increased numbers of red cells deliver more oxygen to the tumor cells and thereby increase their activity across the board, including with respect to invasion, proliferation, and metatstasis?

On one hand we're developing drugs to halt and reverse angiogenesis while on the other hand we're helping the tumor to obtain more oxygen with existing vasculature.

And nobody in charge foresaw that?

At the 12th annual NCCN conference last year, an executive with United Health Group, pointed out that in reviewing records of patients who were prescribed the drug erythropoietin, 44% of those patients had blood work-ups that would indicate they were not anemic.

Amazing how they can apply differing standards for proof or benefit when profit is involved! The profit motive did influence some doctors' decisions.

Federal laws bar drug companies from paying doctors to prescribe medicines that are given in pill form and purchased by patients from pharmacies. But companies can rebate part of the price that doctors pay for drugs, like the anemia medicines, which they dispense in their offices as part of treatment. The anemia drugs are injected or given intravenously in physicians’ offices.

Doctors receive the rebates after they buy the drugs from the companies. But they also receive reimbursement from Medicare or private insurers for the drugs, often at a markup over the doctors’ purchase price.

"It's clear that these drugs were overused because we've seen sales drop so dramatically in the past year without seeing reports of people dying in the streets," said Dr. Charles Bennett, a professor at Northwestern University, who authored the most recent analysis of anemia drug risks.

http://www.businessweek.com/ap/financia ... 8LIK00.htm

Past thread from lung cancer news forum about this problem:

http://lchelp.org/l_community/viewtopic ... highlight=

The problem is that few drugs work the way oncologists think and few of them take the time to think through what it is they are using them for.

It's still a chemotherapy concession. Although the new Medicare bill tried to curtail the drug concession, private insurers still go along with it. What needs to be done is to remove the profit incentive from the choice of drug treatments.

When are they going to take physicians out of the retail pharmacy business and force them to be doctors again!!!

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  • 6 months later...

Some cautionary information about being "overtreated" with anemia drugs. A study, published in the Canadian Medial Association Journal, suggests patients with anemia due to chronic disease are being dangerously overtreated. Anemia may actually help heal the body rather than harm it, says the new study.

Dr. Ryan Zarychanski, the study's co-author and a scientist at the Ottawa Health Research Institute, feels that doctors have been taught for generations that anemia is bad and they want to help their patients by treating it. However, they failed to consider that anemia may be adaptive and may be exactly the response that the body needs at that time.

Tired blood (anemia) involves a shortage of healthy red blood cells to carry oxygen to the body tissues. In the past, blood transfusions were the only way to treat anemia, until a drug derived from erythropoietin (EPO), a hormone that stimulates bone-marrow cells to produce red-blood cells.

Dr. Zarychanski pointed to evidence that suggests anemia is an evolutionary response to illness occuring in humans. The body has adapted over thousands of years to be anemic at times of stress because it needs to conserve energy. It needs help to fight infection. And when you're anemic, bacteria doesn't grow so well in the blood (an evolutionary response to infection before antibiotics).

In general, healthy adults have red blood cell levels of 14 grams or more per 100 millilitres of blood, while patients are considered to need treatment if their levels are below 10 grams. Patients with mild to moderate anemia (those with levels between 10 and 14 grams) would be better off not being treated.

What Dr. Zarychanski argues is that we should exercise some caution when thinking the best treatment is to automatically transfuse or give drugs to correct anemia.

Source: Ottawa Health Research Institute

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  • 2 months later...

Increased death rates among cancer patients taking erythropoiesis-stimulating agents were supported in a large meta-analysis.

Among nearly 14,000 patients in 53 studies, those taking the anemia drugs were 17% (95% CI 6% to 30%) more likely to die during the study, and their overall survival chances were reduced by 6% (95% CI 0% to 12%), reported Julia Bohlius, M.D., M.Sc.P.H., of the University of Bern in Switzerland.

The findings, disclosed at the American Society of Hematology meeting, confirmed results reported earlier in individual studies.

The trials included Epogen, Procrit, NeoRecormon and Aranesp. The analysis was notable for relying on full data on each patient, contributed by the trial sponsors and individual investigators, not on outcome data as published.

And in fact, the on-study mortality results were higher than previously published. On-study mortality was defined as death from any cause occurring from randomization to four weeks after the active study's end. Overall survival was measured from randomization to the end of available follow-up.

When the patient pool was limited to about 10,000 patients treated with chemotherapy, the relationship between erythropoiesis-stimulating agents and mortality fell just short of statistical significance.

On-study mortality in the chemotherapy population was increased by 10% for those taking the anemia drugs (95% CI -2% to 24%), and the overall death rate was increased by 4% (95% CI -3% to 11%), the researchers found.

The results changed little when the researchers controlled for known risk factors.

Age, sex, hemoglobin, hematocrit at baseline, type and stage of tumor, and type of study were among the factors researchers took into account.

Patients getting no cancer treatment showed a 33% increase in on-study mortality if they were receiving erythropoiesis agents (95% CI 7% to 67%).

There were even higher increases in patients receiving other forms of cancer treatment (52% for chemoradiation, 52% for radiation alone, and 53% for "other" non-chemotherapies), but these did not reach statistical significance.

Moreover, a test for interaction among all the non-chemotherapy patient groups yielded a P value of 0.42.

Co-author Andreas Engert, M.D., of the University of Cologne in Germany, said the specific reasons for the increased deaths associated with erythropoiesis agents remained unclear, but on the basis of more recent studies, most of the excess deaths are probably from thromboembolic events.

The American Society of Hematology and the American Society of Clinical Oncology would convene a new guideline panel early in 2009 to consider revisions derived from these findings and other developments since the existing version was published.

Since the current guideline was produced, the FDA had required a boxed warning on epoetin and darbopoetin about increased mortality risks for cancer patients.


Bohlius J, et al., "Recombinant human erythropoiesis stimulating agents in cancer patients: individual patient data meta-analysis on behalf of the EPO IPD Meta-Analysis Collaborative Group" Blood 2008; abstract LBA-6.

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  • 4 months later...

A recent review in the Lancet suggests that using erythropoiesis-stimulating agents like Aranesp, Epogen and Procrit may reduce fatigue and combat anemia in cancer patients, while promoting tumor growth, hasten their deaths from cancer and increase their risk of early death from strokes and other cardiovascular events. The study combined data from nearly 14,000 patients in 54 clinical trials.

Although the FDA had slapped a black box warning on the drugs, the study, which was funded by firms that made them, suggested that doctors explain to their patients that treatment of anemia with EPO agents may improve their quality of life by reducing anemia and fatigue, but their survival may be shortened. According to a MedPage Today analysis of the study, the drugs, which stimulate red blood cell production, increased mortality by 17 percent.

Federal laws bar drug companies from paying doctors to prescribe medicines that are given in pill form and purchased by patients from pharmacies. But companies can rebate part of the price that doctors pay for drugs, like the anemia medicines, which they dispense in their offices as part of treatment. The anemia drugs are injected or given intravenously in physicians' offices. Doctors receive the rebates after they buy the drugs from the companies. But they also receive reimbursement from Medicare or private insurers for the drugs, often at a markup over the doctors' purchase price. I am reminded it is still a "chemotherapy concession."

Last year, U.S. Oncology, which funds, develops and helps manage 443 cancer centers in 39 states, complained that patients were harmed by new Medicare coverage policy for anemic cancer patients. The Centers for Medicare & Medicaid Services (CMS) decision limited ESA (erythropoiesis-stimulating agents) treatment to a maximum of eight weeks after a chemotherapy session. It also required physicians to wait until hemoglobin levels dropped below 10 g/dl before starting therapy.

Because CMS did not receive any documented cases of negative outcomes from the oncology community, it stuck to its decision. The FDA backed CMS' National Coverage Decision (NCD), which limited use of the drugs because they have been shown to spur tumor growth. The FDA believed the approved labeling and CMS' NCD were generally consistent in their recommendations regarding the use of pharmaceutical EPO in patients with cancer undergoing chemotherapy.

However, major insurance companies had not embraced the CMS protocol. It was a "shot over the bow" by the oncology community of government stepping directly into patients lives and saying that they know what is a better course of treatment than doctors. During the ensuing year, we found out that drugs, given by injection, had been heavily advertised, and there was gathering evidence that they had been overused, in part because oncologists could make money by using more of the drug.

Resulting studies had suggested the drugs may make the cancer worse. Much of that evidence came from studies in which patients were treated more aggressively than the drugs' labels recommended. The FDA found mounting evidence of documented effects on survival, tumor progression and thrombotic events which required reassessment of the net benefit of this class of drugs.

Gee, could it be that increased numbers of red cells deliver more oxygen to the tumor cells and thereby their activity across the board, including with respect to invasion, proliferation and metastasis? On one hand we're developing drugs to halt and reverse angiogenesis while on the other hand we're helping the tumor to obtain more oxygen with existing vasculature.

Having said all of this, physicians, scientists and the public occasionally apply their own judgement and determine when the existing evidence is sufficient to support a personal decision to adopt - as opposed to impose upon others - certain drug treatments. No wonder the National Coalition for Cancer Survivorship emphasized the need for drastic changes in how physicians are reimbursed for care. Reward doctors for whole patient care - not just treatments.

http://www.medpagetoday.com/HematologyO ... logy/14007

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  • 2 months later...

A new review of data confirms that erythropoietin - a drug to treat anemia in many cancer patients - might be harmful. The review found that patients with head and neck cancers who received erythropoietin in combination with radiation had poorer outcomes than those who received radiation treatment alone.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Severe anemia in cancer patients can lead to decreased oxygen supply to tumor cells. A lower level of oxygen in tumor cells is associated with more rapid tumor progression and a poorer response to therapy. Many use erythropoietin, or EPO, a hormone that controls red blood cell production, to correct anemia.

"It has therefore been thought logical that using erythropoietin to correct anemia before or during chemotherapy, radiotherapy or both would improve prognosis," the review authors write.

Dr. Philippe Lambin and colleagues at the MAASTRO (Maastricht Radiation Oncology) Clinic in the Netherlands conducted the review.

The investigators analyzed data from five published clinical trials that looked at whether combined radiation and EPO was better than standard radiation therapy alone in the treatment of head and neck cancers. Nearly 1,400 patients were included in the analysis. The researchers compared overall survival, the length of time during and after treatment in which the cancer did not progress, local tumor control and toxicity in the two different treatment groups.

Researchers found that patients who received EPO had significantly worse overall survival compared to patients who did not receive the drug. In addition, patients who took EPO had significantly shorter times before their cancers worsened.

Data included in the review suggest that decreased survival rates in cancer patients who took EPO were not due to some toxic effect of the drug itself, such as an increase in deaths due to blood clots. Instead, researchers have hypothesized that the drug might actually cause some types of tumors to grow.

Barbara Burtness, M.D., chief of the Head and Neck Medical Oncology division at the Fox Chase Cancer Center in Philadelphia, commented on the use of erythropoietin in head and neck cancer.

"The primary use of erythropoietin in cancer patients is to raise hemoglobin when patients become anemic, either because of the cancer or because of a side effect of the cancer treatments," she said. "It's been a part of practice for a long time."

Burtness said that there has been a specific reason for studying EPO in head and neck cancers. "When radiation treatments are given for bulky cancers in the head and neck area, it's thought that cancer cells that don't have a high oxygen content are less susceptible to being killed by radiation. The hypothesis has been that if you could correct a patient's anemia, there would be more red blood cells traveling to the area of cancer. This would lead to correction of the low oxygen content in the tumors - and the patient would be more likely to respond to the radiation treatment," she said.

"But what we've been hearing for some time is that erythropoietin is actually making cancer outcomes worse," she said.

She said the United States has tightened guidelines EPO use in response to data from recent studies. "Giving erythropoietin can have a negative impact on survival. We certainly are not using it here [at Fox Chase Cancer Center]. Among our patients who've received radiation elsewhere, its use does not appear to be common."

Manufacturers promoted EPO to improve anemia, and to help anemic patients to feel better overall. However, the U.S. Food and Drug Administration has issued several public health advisories underscoring the possible risks of using EPO in cancer, including faster tumor growth and early death. The FDA warnings also say that EPO does not improve symptoms associated with anemia, such as fatigue. Nor does EPO improve a patient's quality of life or sense of well-being, the advisories say.

The authors of the review conclude that patients with head and neck cancer should not receive EPO as an addition to radiation therapy.

Source: Health Behavior News Service and GoozNews on Health

Drug therapy for the management of cancer related fatigue

http://www.cfah.org/hbns/archives/viewS ... gDocID=527

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  • 7 months later...

Nearly two years after a Food and Drug Administration advisory committee called for restrictions on the use of red blood cell-stimulating drugs in cancer patients (erythropoiesis-stimulating agents or ESAs), the agency unveiled a stringent risk management plan that should further lower use of the drugs, which are already in freefall in cancer patients. The plan, which affects Amgen's Aranesp and Epogen and Johnson & Johnson's Procrit (manufactured by Amgen and identical to Epogen), requires the companies:

Register oncologists who prescribe the drugs;

Educate them about their risks, which include tumor progression and earlier death; and

Fully inform patients about the risks with an updated medication information guide, both at the time they are initially treated and every time treatment is given; and

Obtain signatures from patients that they've been apprised of the risks.

The updated medication guide will contain information for chronic and end-stage renal disease patients, who also get ESAs for anemia. But renal physicians will not be facing the same registration and education requirements.

The company was given a year to come into full compliance. Officials at a press briefing yesterday were uncertain what would happen to oncologists or the companies if they prescribe or use the drugs without giving the proper warnings.

The program is called, appropriately enough, APPRISE. And while it's tough, it's not unprecedented. The FDA adopted a similar registration program for some opioids.

When pressed by a reporter on why it took so long to come up with the program, Richard Pazdur, head of the oncology office at the Center for Drug Evaluation and Research at FDA, said "this took many many months of discussion. It's a delicate balance. We don't want to interfere in a draconian fashion with the practice of medicine."

Pazdur distinguished between patients undergoing therapy where there is a chance of cure, and those receiving palliative care for incurable cancers. In the latter case, patients may opt for the greater energy that comes from alleviating cancer- and chemo-related anemia, even if it results in a shorter end game.

"The risks-benefit balance is a delicate one," Pazdur said. The goal of the program wasn't to restrict use of the drugs, but "to help patients make the best choice given their individual situation."

The failure to simultaneously force the companies to reeducate the renal physician community was disappointing. There's mounting evidence that high doses of ESAs in renal disease patients is associated with increased risk of heart attacks, strokes and earlier mortality. Many of these patients are poor and unaware of the quality of care they receive at dialysis centers. They, just as much as cancer patients, need to be informed about the risks posed by overuse of ESAs.

Source: Gooznews on Health

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what are effects on someone getting aranesp who does not have cancer Greg??? i realized sometime after posting this tat it may or may not have contributed to My late wifes death and cancer spread also but I have a parent with health issues who gets aranesp about 1 every 4-6 weeks I believe for his blood counts to stay up!

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All the information written about this is saying that caution should be given when giving EPO to cancer patients, expecially those receiving chemotherapy.

Dr. Herman Kattlove is a retired medical oncologist. For seven years, he was a medical editor for the American Cancer Society where he helped develop much of the information about specific cancers that is posted on the society's website. He had been writing about the caveats of using EPO on his private cancer blog over the last few years.

Recent studies have suggested that in cancer patients with a reasonably long life expectancy, the benefit of using epoetins does not outweigh the risk of tumor progression and shorter overall survival. It was recommended to use the lowest dose of ESAs to gradually increase the hemoglobin concentration. Nothing greater than 12 g.dl.

Research in the area of whether blood transfusions are safer than ESAs in cancer patients have been laden with endpoint problems. Work has focused on hemoglobin levels and transfusion rates, not overall survival.

Health care professionals need to consider the risks of increased tumor progression and decreased survival in patients with cancer when prescribing ESAs. ESAs should be used in patients with cancer only when their anemia is due to chemotherapy and only at the lowest dose necessary to avoid the need for blood transfusions.

The Cochrane Collaboration published a study that cancer patients are more likely to die if they have received the red cell stimulating hormone erythropoietin or darbopoietin (EPO). Epo is given to prevent or lower the chance that a cancer patient, especially one on chemotherapy will become anemic. But anemia is not a terrible thing. Most patients with cancer, either on or off chemotherapy complain of fatigue. Many of them are anemic. So the people who make Epo marketed the drug to doctors as a way of countering this fatigue.

The problem is that although severe anemia can cause fatigue, mild anemia, which is typical of most cancer patients, doesn’t. Their fatigue isn’t caused by the anemia. It is caused by the cancer or the chemotherapy. Almost all patients with advanced cancer or receiving chemotherapy complain of fatigue even though most are not very anemic. Blood transfusion of those with more severe anemia does little for the fatigue.

But the pharmaceutical companies are big marketing machines and Epo, being a biologically produced drug is safe from generic competition. So there is money to be made and pushing doctors to give this drug has been very profitable for Amgen, its main manufacturer.

In fact, Lee Newcomer, with United Health Group, had stated at the 12th annual conference of the National Comprehensive Cancer Network, 44% of patients having blood work-ups indicated they were not anemic. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society, reiterated that Newcomer was right on the spot on this.

The Cochran Collaboration has reviewed and summarized the outcomes of some nearly 14,000 cancer patients and found that those who received Epo were about ten percent more likely to die than patients not receiving the drug. These studies were all randomized controlled trials, which means that half the patients did not get the Epo. But, unfortunately, those who did died more quickly. The two major ideas about why people died is faster growth of the cancer and problems with blood clots.

So besides being problematic, EPO can be a killer that should probably not be routinely given to cancer patients. Severe anemia can be treated with blood transfusion. It is generally far safer than Epo and cheaper.

Like you, I have a parent with health issues who used to receive Procrit injections for low levels of anemia. She was on Medicare and Medicare had already established guidelines for its use. So her family doctor adhered to those guidelines. Later, we found out that anemia is actually not harmful.

For a history of this issue over the last three years read this posting, expecially "Anemia may be adaptive to the body."


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  • 1 year later...

Patients May Die When Doctors Moonlight as Big Pharma's "Key Opinion Leaders"

As the crimson sun slipped into the gray Pacific Ocean, a multibillion-dollar drug deal took shape. A group of board-certified doctors greeted each other in a private room at a luxury hotel in California. The oncologists were big buyers of an anti-anemia drug called Procrit, sold by Ortho Biotech, a Johnson & Johnson (J&J) division. That Friday evening, the company toasted its top clients and their wives with bottles of Beaujolais, porterhouse steaks and free weekend accommodations.

The event could have been just another "grin and grip" affair, but there was a catch: J&J wanted to pump the sales of its biotech drug to beat its rival Amgen and its anti-anemia drugs. "The idea," as J&J drug rep Dean McClellan later explained, "was to get the docs to increase their Procrit dosage to 40,000 units."

There was just one problem. Regulators had approved a weekly drug dose of 30,000 units, and J&J was prohibited by the Food, Drug, and Cosmetic Act (FDAC) from marketing its drugs in unapproved ways. But the doctors could prescribe in any "off-label" manner they wanted. So, McClellan, a star rep and medical consigliere, led a "discussion" about high-dose experiments. Taking his cue, one physician explained how he routinely injected patients with 40,000 units of Procrit. Another oncologist pumped his people with 10,000 units for ten consecutive days - triple the approved amount. "That seems a little extreme," said McClellan, frowning.

"Oh no," the doctor said. "I haven't seen any side effects so far."

A few months later, Procrit sales hit the $1 billion mark, beating Amgen by a hair. The resort trip had certainly helped. But it was just one part of an expansive, long-running off-label marketing campaign, according to sales documents. Slowly but surely, oncologists around the country began administering so many high Procrit doses that, in time, the off-label therapy became the "community standard."

There were problems since insurers don't always reimburse doctors for off-label use. In fact, when Medicare refused to pay the Arizona Cancer Center, a huge client, for its high-dose Procrit injections, an Ortho manager ghost wrote a letter on behalf of its chief oncologist Daniel Von Hoff. After a few more company calls - ipso presto! - the center began receiving more than $1 million in Medicare payments for the illegal therapy. As McClellan claimed in a whistleblowing suit, the cancer market grew so saturated with high doses, that six years later the Food and Drug Administration finally approved them.

The decision might have been defensible had the 40,000-unit regime had been proven to be safe and effective. But independent research later revealed that cancer patients died sooner than expected, and company trials found an alarming number of dialysis patients suffered strokes and heart attacks. Meta-studies showed that 17 percent of patients died from the drug, and stories told of blood counts so high, patients actually spit up blood and choked on their own tumors. Turns out there was little scientific evidence that Procrit, and its cousins Epogen and Aranesp, actually helped people at any dosage.

Last summer, regulators announced that the drugs should be avoided entirely by most patients. "It turns out many people are better off taking placebos," said Dennis Cotter, president of Medical Technology and Practice Patterns, a nonprofit research institute.

What this illustrates is that drug companies can create entire cultures of over-prescribers for untested, even fatal indications, and that doctors can be easily corrupted. In light of a flurry of recent federal settlements for off-label marketing crimes, it also underlines how you, dear taxpayer, foot the bill for reckless marketing.

In the case of Procrit, the J&J unit formed advisory committees made up of academic physicians and clinical oncologists. These key opinion leaders (KOLs) were paid honoraria of at least $1,000 for every speech they delivered touting off-label use. McClellan selected some pliant clients to be the featured speakers. "Some guys wanted to give three or four speeches a weekend so they can get three or four thousand dollars," he said. A few actually did. Many talks were delivered at company "conferences" organized for other doctors, who earned hourly credits toward their annual continuing medical education (CME) units, required by state licensing boards. As if that wasn't enough, Ortho also paid physicians for their rooms, meals and transportation.

Ortho eventually assembled boards of KOLs who specialized in every type of cancer. According to sales documents, the goal was "to build thought leader endorsement [sic] to establish Procrit as standard of care," not just for approved indications such as AIDs and chemotherapy, but for cancer-related fatigue, depression, and other off-label indications.

These friendly prescribers were not Dr. Feelgood types working the tenderloin. They were distinguished professors from respected institutions such as John Hopkins University, Harvard Medical School, University of Chicago, Memorial Sloan-Kettering Cancer Center, Emory University Hospital, Cornell University, Long Island Jewish Medical Center, University of Texas MD Anderson Cancer Center, and others. Dr. Nicholas J. Vogelzang of the University of Chicago was a paid spokesman for the Fatigue Coalition, a group bankrolled by Ortho. Dr. John Glaspy of UCLA penned a seminal article in the Journal of Clinical Oncology that drew rosy conclusions about high-dose Ortho-sponsored studies.

Dozens of other doctors agreed to "influence their colleagues to use Procrit" for unapproved indications such as cancer-related fatigue. One was Dr. von Hoff, the director at the Arizona Cancer Center. He collected advisory fees and perks from not just Ortho, but from about 30 other pharmaceutical firms, earning directors' fees for sitting on several companies' boards. "When I saw how many shares he owned in biotech and drug firms, my jaw dropped," McClellan later said. Many others, like Dr. Jerome Groopman of Harvard Medical School, performed J&J-funded clinical trials. He was paid to sit on Procrit's "fatigue" advisory board and was quoted often in The New York Times extolling the drug, according to public records.

Groopman also penned a bestseller called "How Doctors Think." In it, he talks about the importance of talking with patients about their diagnosis and treatments. But Groopman doesn't explain what role Big Pharma checks and trips play in his own decision making. This is noteworthy since he goes on about the influence of high-pressure drug reps and the need for physicians to weigh scientific assessments against "going with your gut."

Clearly, even esteemed doctors were swayed by Procrit's marketers. In reviewing the basic science research behind these costly anti-anemia drugs, Dr. Charles Bennett of Northwestern University found that physicians and investigators who collected money from the two drug makers were "less likely to criticize the safety, effectiveness, or cost-effectiveness of drugs" and "more likely to endorse novel and less proven treatments" like off-label. No matter what prescribers say, they seem to have indeed been bought by golf trips, grants and banquets.

The overprescribing of anti-anemia drugs roared alongside an astonishing rise in American health care expenses. For several years, Procrit and the others topped Medicare's reimbursement list. By 2007, the drugs' domestic sales approached $11 billion a year. So far, US taxpayers have shelled out more than $60 billion over the past 20 years, reimbursing doctors, KOLs and hospitals for a drug that never worked as advertised.

McClellan's whistleblowing case may be in limbo. But many prestigious doctors will soon wind up in the confessional. Thanks to the Physician Payments Sunshine Act, doctors who accept speaking fees, meals, travel, stock options, or any other compensation from drug or medical device companies will soon see their names - and their gifts - revealed publicly on the web. The rule is part of the Patient Protection and Affordable Care Act, aka "Obamacare." Data collection was supposed to begin this January, but the first report won't appear until March 31, 2013. When that day dawns, patients will gain some insight into their treatments. Was that off-label prescription supported by scientific evidence; or did my doctor "go with his gut?" If so, how often was that gut filled by the maker of my medication?

From Kathleen Sharp's book, "Blood Feud: The Man Who Blew the Whistle on One of the Deadliest Prescription Drugs Ever."

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Randy and Greg - am so glad to see these posts. When I was going through chemo my oncologist wanted to give me aranesp. I googled it - read what it said about it causing tumors to grow - and wondered why the heck they wanted me to take this when I'd just spent weeks and weeks going through radiation and chemo to get rid of it!! My insurance company would not OK a transfusion - so they just kept pushing it - said it would make me feel so much better. I asked point blank if they knew what the possible side effects were and, unbelieveably to me, they did and they were still put out with me for refusing.

I've seen so many other people post that they were getting this to increase their red blood cell count.

I hope a lot of people see this - you've done them a big favor.


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"Dozens of other doctors agreed to 'influence their colleagues to use Procrit' for unapproved indications such as cancer-related fatigue. One was Dr. Von Hoff, the director at the Arizona Cancer Center. He collected advisory fees and perks from not just Ortho, but from about 30 other pharmaceutical firms, earning directors' fees for sitting on several companies' boards. 'When I saw how many shares he owned in biotech and drug firms, my jaw dropped,' McClellan later said. Many others, like Dr. Jerome Groopman of Harvard Medical School, performed J&J-funded clinical trials. He was paid to sit on Procrit's 'fatigue' advisory board and was quoted often in The New York Times extolling the drug, according to public records."

In 2010, Dan Von Hoff got the Karnofsky award from the American Society of Clinical Oncology (ASCO), which is sort of a lifetime achievement award for clinical research. This is a nuclear explosion for clinical oncology. I'm wondering who was involved in the Harvard side of it? Interestingly, it is the highest levels of academia who are most tainted. One in particular, Dan Von Hoff. These ivory tower docs were the culprits. Unfortunately, this will probably play out as one more cudgel to beat the more reasonable and gentle practitioners, who either largely avoided such abuse or were led down the path by the scholars, who will themselves skip out unfazed.

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Which just goes to prove that patients really do have to do their own research - which unfortunately can be a daunting task for most us -sometimes not easy to understand, and if you are sick from the effects of chemo this can be even harder unless you have a family member who can advocate for you and keep on my research.

Thanks, Greg, for all the information you provide.


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