In what's being called the largest settlement ever for a biotech company, Amgen Inc. finalized a $612 million agreement Tuesday to resolve federal civil claims stemming from 10 whistleblower suits alleging off-label marketing of several of its top-selling drugs.

The bulk of the settlement will be paid to the U.S. government, with $24.8 million going to the states, to resolve claims that, due to its marketing practices, Amgen caused false claims to be submitted to Medicare, Medicaid and other government insurance programs.

The civil settlement comes on top of the $136 million fine and $14 million forfeiture the Thousand Oaks, Calif.-based company agreed to pay Tuesday as part of a criminal misdemeanor plea deal involving its marketing of Aranesp (darbepoetin alfa), bringing Amgen's total payment to $762 million. (See BioWorld Today, Dec. 19, 2012.)

In addition to Aranesp, the civil settlement covers Amgen's promotion of Epogen (epoetin alfa), Neupogen (filgrastim), Neulasta (pegfilgrastim), Enbrel (etanercept) and Sensipar (cinacalcet). The whistleblower suits also alleged that Amgen knowingly reported inaccurate pricing information such as average sales prices, best prices and average manufacturer prices for several drugs.

"Amgen acknowledges that mistakes were made, and we did not live up to our standards," said Cynthia Patton, senior vice president and chief compliance officer at Amgen. As part of the criminal and civil settlements, the company has entered a corporate integrity agreement, which "is aligned with the significant changes and enhancements we have made to our compliance program and demonstrates our commitment to fostering a culture of compliance at Amgen," Patton added.

The criminal charge stemmed from the marketing of Aranesp at much higher dosages/less frequent administration than what the FDA had approved in an effort to capture market share from Procrit, Janssen Products LP's epoetin alfa drug.

Amgen touted the convenience of monthly dosing over twice-monthly dosing for kidney patients and every-other-week dosing vs. weekly dosing for cancer patients, using dosages two to four times higher than what the FDA had approved, Marshall Miller, acting U.S. attorney for the Eastern District of New York, said.

Until the FDA ordered a boxed warning in 2007 against the use of Aranesp to treat anemia in cancer patients not undergoing chemotherapy due to an increased risk of death, the company promoted that off-label use, according to the Department of Justice (DOJ).

When the historic settlements were finalized Wednesday, Jenny Durkan, the U.S. attorney for the Western District of Washington, said, "This sends a powerful message to pharma companies. . . . Drugs should be prescribed because they make people better, not because they make companies money."

But the settlements may be sending another message to the biopharma industry: The DOJ is raising the bar on off-label marketing and the interaction drugmakers can have with doctors.

Under current FDA rules, sales representatives may respond to doctors' questions and share journal articles about off-label use when asked. In the Amgen case, the DOJ expressed concern with how those questions are raised. It blasted a practice it called "reactive marketing" in which Amgen allegedly trained sales representatives to elicit questions from doctors about off-label use. Such practices are an effort to circumvent the law and provide a smokescreen for illegal marketing, the department said.

The criminal investigation also focused on the adequacy of the journal articles Amgen representatives gave to doctors. The studies cited in the articles were often the ones Amgen had submitted to support an expanded label, the DOJ said, but the FDA rejected them "as insufficient to support the safety and efficacy of those off-label uses."

Although the civil and criminal settlements weren't finalized until Wednesday, Amgen absorbed the shock last year when it reported a $780 million charge in the third quarter after reaching agreements in principle. As a result, shares of Amgen (NASDAQ:AMGN) hardly flinched Wednesday, dropping less than 1 percent – about 80 cents – to close at $88.49.