Amgen's troubles keep compounding; Aranesp studies reveal greater risks

amgens-troubles-keep-compounding-aranesp-studies-reveal-greater-risksIt seems that when it comes to Aranesp, its blockbuster anemia drug, Amgen (AMGN) just can't catch a break, nor for that matter, create one. Recently, Amgen was hit with a double whammy -- a lawsuit and an unfavorable study of the drug. On Tuesday, yet another study confirmed that cancer patients who took anemia drugs were twice as likely to develop blood clots as other patients, while transfusion rates remained the same.

The decade-long study of 56,210 cancer patients conducted by Dr. Dawn L. Hershman and her colleagues at the Irving Comprehensive Cancer Center at Columbia University Medical Center in New York adds to earlier evidence about the risks of anemia drugs, and further suggests that those risks may outweigh the benefits.

Aranesp (darbepoetin alfa) is an injectable drug that stimulates the production of red blood cells in the body. Often, patients who undergo dialysis or chemotherapy develop severe anemia that leaves them weak. Aranesp helps them recover from the tough treatments faster and reduces the need for transfusions. Amgen's drug Epogen and Johnson & Johnson's (JNJ) Procrit belong to the same family of drugs, called erythropoiesis-stimulating agents (ESAs).

Concerns over these drugs have been mounting in recent years after a series of studies found that high doses can lead to increased risks of heart attack, stroke, heart failure and tumor growth in some patients. As a result, in 2007, the Food and Drug Administration issued a black-box warning -- the strongest warning possible about potential side affects -- for Aranesp, Epogen and Procrit. Aranesp sales have declined in recent years as a result.

Less than two weeks ago, a new study published in The New England Journal of Medicineraised fresh safety concerns about the widely used anemia medicine. The study found that Aranesp nearly doubled the risk of stroke in people with diabetes and chronic kidney problems who are not yet sick enough to need dialysis.

Aranesp's Risks Found Higher, Its Benefits Lower

While this was not news, the 4,038 patient study was the largest ever of its kind, and the only one that compared the blood-boosting drug to a dummy treatment. The medicine's ability to prevent heart attacks, kidney failure or other problems have not been proven. Worse, concerns rose that they may worsen survival in certain cancer patients, especially at higher doses.

According to the AP, Amgen, which sponsored the study, said the magnitude of the risk surprised it and that it would update the label, which already has this warning on it: WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION. Aranesp did reduce the need for transfusions, but only modestly reduced fatigue.

Still, what's surprising in Tuesday's results, which were published in The Journal of the National Cancer Institute, is that unlike previous studies, researchers found that blood transfusion rates among these patients remained steady. About 27% of the patients, 15,346, received an ESA, but the number of patients receiving the drugs to prevent anemia and fatigue increased dramatically, from 4.8% in 1991 to 45.9% in 2002. And yet, the rate of transfusions per year has remained constant, at 22%, the investigators reported. This may be the biggest blow to Aranesp yet, as the main reason for the drug's use was to reduce the rate of transfusions. Attempts to reach the company were not immediately answered.

Not only that, but among those on the anemia drugs there was increased risk of thromboembolic events (the production of blood clots in the legs that can move to the lungs and elsewhere and could be potentially fatal) -- 14.3% in patients on the drugs vs. 9.8% in patients not taking the drugs.

Doctors Got Kickbacks to Prescribe, Lawsuit Alleges

But unfavorable studies for one of its top selling drugs aren't Amgen's only problem. New York Attorney General Andrew M. Cuomo, who simply can't resist the spotlight, announced that New York and 14 other states are filing a lawsuit against the biotechnology giant following an investigation that found a nationwide kickback scheme to boost drug sales. The suit is seeking triple damages, plus civil and monetary penalties.

To be sure, these are serious allegations, especially in light of these unfavorable studies. The lawsuit claims that Amgen, along with the International Nephrology Network, a specialty group purchasing organization, and ASD Healthcare, a wholesaler owned by AmerisourceBergen Corp. (ABC), offered kickbacks to medical providers to increase sales of Aranesp. They also allegedly encouraged medical providers to bill third-party payers such as Medicaid for samples of Aranesp that they were provided at no cost.

In a nutshell, Amgen bribed doctors to prescribe Aranesp -- perhaps when not clinically necessary and perhaps at higher doses than necessary -- and convinced them to bill payers for free samples. According to bNet, what Amgen may find most difficult to defend are two PowerPoint slideshows and an email from colleagues of Amgen CEO Kevin Sharer discussing the scheme. A 2006 congressional report says anemia medications are the single biggest drug expense for Medicare, Medicaid, and other taxpayer-funded insurance programs.

"Drugs should be prescribed to patients on the basis of need, effectiveness and safety, not on a corporate giant's promise of an all-expense paid vacation," said Cuomo. "In an egregious violation of the law, Amgen allegedly bribed medical providers and left taxpayers footing the bill for free drug samples."

In response Amgen said: "We believe that the allegations are without merit, and we look forward to the opportunity to examine these matters with the states before the Court." Mary Klem, director of Amgen's corporate communications, added that "Because this lawsuit is now in litigation, we are limited in our remarks about matters pending before the Court," but added, "Amgen has a solid compliance program and Code of Conduct called "Do The Right Thing," and we expect that all of our employees to follow it at all times."

Aranesp's total sales have reached over $11 billion dollars since the drug was first introduced into the marketplace. In 2008, Amgen's sales totaled $15 billion. Worldwide sales of Aranesp, once Amgen's best-selling drug and still one of its top-sellers, totaled about $3.1 billion in 2008, but that was 25% lower than in 2006. In the third quarter, sales of Aranesp dropped 19%.

Other Drugs Also Experiencing Problems

All of these setbacks add to other recent ones Amgen has experienced. The Thousand Oaks, Calif.-based company has been placing its hopes in its experimental bone drug denosumab, but the FDA delayed its approval for several key conditions just last month. Amgen said it is confident it can "quickly respond to the FDA's requests," but for now, the only thing one can be certain of is that there has been yet another delay in denosumab reaching the market.

Last week, after a tough month, Amgen's stock finally climbed, despite a study showing that its cancer drug Vectibix failed to meet its secondary endpoint and improve overall survival as an initial treatment for advanced colorectal cancer. But some believe this could actually help boost sales as it supports previous results.

In the previous study, which met the primary endpoint of significantly prolonging progression-free survival in the first-line treatment of patients without a certain gene mutation, the latest results also show increased survival of more than four months in patients without a specific gene mutation, but the data didn't meet statistical significance. This could support earlier use and wider approval of the drug in colorectal cancer -- where it competes against Erbitux, sold by Eli Lilly & Co. (LLY) and Bristol-Myers Squibb (BMY).

The largest independent biotech firm in the world has to face all these hurdles now in its path. Not only there are even greater concerns regarding one of its top sellers, the company is being sued for marketing it aggressively. Not only are its sales slowing as a result of these concerns, Amgen's most promising drug for its future growth keeps hitting brick walls on its way to market.
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