“Promoting drugs for unapproved uses is potentially harmful,” said Acting Attorney General Hoffman. “This is an important settlement for New Jersey citizens, not only because it requires a substantial payout by Amgen, but also because it includes injunctive terms designed to protect consumers by preventing similar conduct going forward.”

Aranesp is an erythropoiesis-stimulating agent or ESA used to treat certain types of anemia, but is not approved by the FDA for use in treating anemia caused by cancer. Enbrel is used to treat rheumatoid arthritis and plaque psoriasis.

A multi-state investigation of Amgen’s conduct centered on allegations that, despite clinical evidence that Aranesp was of questionable benefit to patients with anemia caused by cancer – and might actually harm such patients -- Amgen promoted the drug to health care providers for off-label (non-FDA-approved) use in treating such patients.

The company also sought to have the off-label use of Aranesp listed in the compendium United States Pharmacopeia (USP) – one of two non-profit drug reference books recognized by the Centers for Medicaid and Medicare Services (CMS) -- in 2003.
(The most common way to obtain reimbursement for an off-label use is to obtain a listing in a CMS-recognized drug compendium.)

According to a State Complaint against Amgen filed in New Jersey Superior Court today along with the Final Consent Judgment:

In October 2003 -- after considerable lobbying by Amgen – USP accepted an indication for Aranesp in the treatment of anemia caused by cancer, and Amgen subsequently promoted Aranesp for that use to health care professionals.

At around the same time, however, two large, randomized controlled clinical trials found an increased risk of death and possible tumor stimulation in cancer patients receiving ESAs that were not approved in the U.S.

Then in May 2004, the FDA’s Oncologic Drugs Advisory Committee met to discuss safety concerns related to increased thrombotic events, tumor progression and decreased survival found in the 2003 controlled clinical trials as they applied to Aranesp (as well as its chief competitor Procrit.)

Despite these growing concerns, Amgen promoted Aranesp to treat anemia caused by cancer.

In January 2007, the results of a study in which patients receiving Aranesp for the treatment of anemia caused by cancer showed an increase in death and no significant reductions in transfusions or improvement in quality of life.

The multi-state investigation of Amgen also focused on allegations that Amgen inappropriately marketed Enbrel to health care providers for the treatment of both mild psoriasis and moderate-to-severe psoriasis.

According to the State’s Complaint:

The FDA sent a Warning Letter to Amgen in February 2005 advising that Amgen’s direct-to-consumer television advertisement “Freedom” overstated the effectiveness of Enbrel and minimized the risks associated with the drug.

In March 2008, the FDA required that a black box warning be added to Enbrel’s labeling. The warning noted that infections –including serious infections that led to hospitalization and death – had been observed in patients treated with Enbrel. These infections included cases of bacterial sepsis and tuberculosis.

In August 2009, the FDA required Enbrel’s black box warning be expanded to inform prescribers and patients that invasive fungal infections -- as well as bacterial, viral and other infections caused by opportunistic pathogens – had been reported with the use of Enbrel. (The black box warning now cautions that lymphoma and other malignancies, some fatal, have been observed in children and adolescent patients taking Enbrel.)
Despite the black box warnings, the 2005 FDA Warning Letter, and Enbrel’s limited approval for use in chronic moderate to severe plaque psoriasis, Amgen promoted Enbrel for off-label use in treating patients with mild plaque psoriasis from 2004 through 2011, and overstated Enbrel’s efficacy in the treatment of plaque psoriasis, the Complaint alleges.

Overall, Amgen is paying a total of $71 million to states participating in the national settlement. In addition to the monetary terms of settlement, Amgen is subject to the following non-monetary terms, among others. Amgen:

• Shall not make, or cause to be made, any written or oral claim that is false, misleading or deceptive in its promotion of Aranesp and Enbrel.

• Shall not represent that Aranesp and Enbrel possess any sponsorship, approval, characteristic, ingredients, uses, benefits, quantities or qualities they do not have.

• Is prohibited from using a pharmaceutical compendium listing or publication to promote Aranesp and Enbrel for off-label use to a health care professional.

• Is prohibited from using a third-party to lobby a pharmaceutical compendium on Amgen’s behalf without notifying the compendium that the third party is acting at Amgen’s request.

In December 2012, Amgen settled with the U.S. Department of Justice to resolve criminal and civil liability claims resulting from its promotion of several drugs, including Aranesp and Enbrel. Amgen pleaded guilty to a misdemeanor count of misbranding relating to Aransep and paid a criminal fine of $136 million, as well as a criminal forfeiture in the amount of $14 million.

Deputy Attorney General Patricia Schiripo, Assistant Section Chief of the Division of Law’s Consumer Fraud Prosecution Section, handled the Amgen matter on behalf of the State.

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